Lung Cancer

The American Cancer Society has updated its screening guidelines for lung cancer, the leading cause of cancer-specific deaths in the United States and the largest driver of potential years of life lost from cancer.

The 2023 screening guidance, aimed principally at reducing lung cancer mortality in asymptomatic but high-risk, tobacco-exposed individuals, expands the age eligibility and lowers both the former smoking history and the years since quitting threshold for screening with low-dose CT (LDCT).

It is based on the most recent evidence on the efficacy and effectiveness of screening and lung cancer risk in persons who formerly smoked, wrote the ACS’s Guideline Development Group led by Robert A. Smith, PhD, senior vice president of early cancer detection science. The new guidelines, which replace the 2013 statement, appear in CA: A Cancer Journal for Physicians.

The primary evidence source for the update was a systematic review of LDCT lung cancer screening conducted for the U.S. Preventive Services Task Force and published in 2021.

The new guideline continues a trend of expanding eligibility for lung cancer screening, which has had low uptake, to prevent more deaths. “Recent studies have shown that extending the age for persons who smoked and formerly smoked, eliminating the ‘years since quitting’ requirement, and lowering the pack-per-year recommendation could make a real difference in saving lives,” Dr. Smith said. “The relative risk of developing lung cancer in people who have smoked most of their life compared to people who never smoked is very high – about 70 times the risk.” Although lung cancer is the third most common malignancy in the United States, it accounts for more deaths than colorectal, breast, prostate, and cervical cancers combined.

The recommendation for annual LDCT for at-risk persons remains unchanged from 2013.

Among the 2023 eligibility changes:

• Age: Expanded to 50-80 years from 55-74 years.
• Smoking status: Changed to current or previous smoker from current smoker or smoker who quit within past 15 years (number of years since quitting no longer a criterion to start or stop screening). Dr. Smith noted that both the 2013 guidelines and other groups’ updated recommendations retained the eligibility cutoff of 15 years since smoking cessation. “But had their risk declined to a level that just did not justify continuing screening?” he asked. “There wasn’t an answer to that question, so we needed to look carefully at the absolute risk of lung cancer in persons who formerly smoked compared with people who currently smoked and people who never smoked.”
• Smoking history: Reduced to 20 or more pack-years (average of 20 cigarettes a day) versus 30 or more pack-years.
• Exclusions: Expanded to health conditions that may increase harm or hinder further evaluation, surgery, or treatment; comorbidities limiting life expectancy to fewer than 5 years; unwillingness to accept treatment for screen‐detected cancer, which was changed from 2013’s life‐limiting comorbid conditions, metallic implants or devices in the chest or back, home oxygen supplementation.

In addition, decision-making should be a shared process with a health professional providing the patient with information on the benefits, limitations, and harms of LDCT screening, as well as prescreening advice on smoking cessation and the offer of assistive counseling and pharmocotherapy.

“Overall, lung cancer screening remains one of the least used early cancer detection modalities in clinical practice. The new guidance opens up lung cancer screening to all former smokers regardless of time of cessation,” said internist William E. Golden, MD, MACP, a professor of medicine and public health at the University of Arkansas for Medical Sciences, Little Rock. “This may promote greater uptake in concert with greater availability of low-radiation CT scanning.”

While agreeing the expanded criteria will enfranchise nearly 5 million current and former U.S. smokers for screening and may reduce deaths, internist Aarati D. Didwania, MD, MMSCI, MACP, a professor of medicine and medical education at Northwestern University, Chicago, warned that increasing actual uptake may be an uphill battle. “The practical part of the equation is seeing that the scans get done. There is often a lag between a recommendation of a yearly test and getting insurance coverage for it, and many disadvantaged people face barriers.” Then there’s the knowledge gap. “Patients and doctors have to know what the new guidelines are and who has access,” she said.

Reaching the target population in rural areas is particularly challenging with the greater distances to imaging centers. Another barrier is that most electronic health records do not identify eligible patients based on smoking and pack‐year history.

In Dr. Didwania’s view, professional medical societies have an important role to play in educating their members, and through them, patients. “Disseminating information about the new recommendations is the first step and would be incredibly helpful.”
 

A brief history of lung cancer screening

1950s: By mid-20th century, the causal association between tobacco exposure and lung cancer became clear and by the late 1950s attempts were made to develop a lung cancer screening strategy for high‐risk individuals, commonly with the combination of sputum cytology and chest x-ray.

1970s: The ACS recommended annual testing for current or former smokers with chest x-ray (and sometimes sputum cytology).

1980: The ACS withdrew the above recommendation for regular radiographic screening after randomized controlled trials failed to yield convincing evidence that such screening saved lives.

2013: After the National Lung Screening Trial found three annual LDCT screenings were associated with a 20% relative mortality reduction, compared with annual chest x-ray, the ACS issued a recommendation for annual screening with LDCT: in persons 55-74 years with a pack‐year history of 30 or more who currently smoke or formerly smoked but had not exceeded 15 years since quitting and had no life-limiting morbidity.
 

Future mortality

Although tobacco controls are expected to reduce age‐adjusted lung cancer mortality in the United States by 79% from 2015 to 2065, 4.4 million lung cancer deaths are projected to occur in this period, the authors stated. “A large fraction of these deaths can be prevented if we embrace the urgent challenge to improve our ability to identify the population at risk and apply our knowledge to achieve high rates of participation in regular [lung cancer screening].”

The study was funded by the American Cancer Society Guideline Development Group and the National Comprehensive Cancer Network. The authors disclosed no relevant competing interests. Dr. Golden and Dr. Didwania had no relevant conflicts of interest to declare with regard to their comments.

The American Cancer Society has updated its screening guidelines for lung cancer, the leading cause of cancer-specific deaths in the United States and the largest driver of potential years of life lost from cancer.

The 2023 screening guidance, aimed principally at reducing lung cancer mortality in asymptomatic but high-risk, tobacco-exposed individuals, expands the age eligibility and lowers both the former smoking history and the years since quitting threshold for screening with low-dose CT (LDCT).

It is based on the most recent evidence on the efficacy and effectiveness of screening and lung cancer risk in persons who formerly smoked, wrote the ACS’s Guideline Development Group led by Robert A. Smith, PhD, senior vice president of early cancer detection science. The new guidelines, which replace the 2013 statement, appear in CA: A Cancer Journal for Physicians.

The primary evidence source for the update was a systematic review of LDCT lung cancer screening conducted for the U.S. Preventive Services Task Force and published in 2021.

The new guideline continues a trend of expanding eligibility for lung cancer screening, which has had low uptake, to prevent more deaths. “Recent studies have shown that extending the age for persons who smoked and formerly smoked, eliminating the ‘years since quitting’ requirement, and lowering the pack-per-year recommendation could make a real difference in saving lives,” Dr. Smith said. “The relative risk of developing lung cancer in people who have smoked most of their life compared to people who never smoked is very high – about 70 times the risk.” Although lung cancer is the third most common malignancy in the United States, it accounts for more deaths than colorectal, breast, prostate, and cervical cancers combined.

The recommendation for annual LDCT for at-risk persons remains unchanged from 2013.

Among the 2023 eligibility changes:

• Age: Expanded to 50-80 years from 55-74 years.
• Smoking status: Changed to current or previous smoker from current smoker or smoker who quit within past 15 years (number of years since quitting no longer a criterion to start or stop screening). Dr. Smith noted that both the 2013 guidelines and other groups’ updated recommendations retained the eligibility cutoff of 15 years since smoking cessation. “But had their risk declined to a level that just did not justify continuing screening?” he asked. “There wasn’t an answer to that question, so we needed to look carefully at the absolute risk of lung cancer in persons who formerly smoked compared with people who currently smoked and people who never smoked.”
• Smoking history: Reduced to 20 or more pack-years (average of 20 cigarettes a day) versus 30 or more pack-years.
• Exclusions: Expanded to health conditions that may increase harm or hinder further evaluation, surgery, or treatment; comorbidities limiting life expectancy to fewer than 5 years; unwillingness to accept treatment for screen‐detected cancer, which was changed from 2013’s life‐limiting comorbid conditions, metallic implants or devices in the chest or back, home oxygen supplementation.

In addition, decision-making should be a shared process with a health professional providing the patient with information on the benefits, limitations, and harms of LDCT screening, as well as prescreening advice on smoking cessation and the offer of assistive counseling and pharmocotherapy.

“Overall, lung cancer screening remains one of the least used early cancer detection modalities in clinical practice. The new guidance opens up lung cancer screening to all former smokers regardless of time of cessation,” said internist William E. Golden, MD, MACP, a professor of medicine and public health at the University of Arkansas for Medical Sciences, Little Rock. “This may promote greater uptake in concert with greater availability of low-radiation CT scanning.”

While agreeing the expanded criteria will enfranchise nearly 5 million current and former U.S. smokers for screening and may reduce deaths, internist Aarati D. Didwania, MD, MMSCI, MACP, a professor of medicine and medical education at Northwestern University, Chicago, warned that increasing actual uptake may be an uphill battle. “The practical part of the equation is seeing that the scans get done. There is often a lag between a recommendation of a yearly test and getting insurance coverage for it, and many disadvantaged people face barriers.” Then there’s the knowledge gap. “Patients and doctors have to know what the new guidelines are and who has access,” she said.

Reaching the target population in rural areas is particularly challenging with the greater distances to imaging centers. Another barrier is that most electronic health records do not identify eligible patients based on smoking and pack‐year history.

In Dr. Didwania’s view, professional medical societies have an important role to play in educating their members, and through them, patients. “Disseminating information about the new recommendations is the first step and would be incredibly helpful.”
 

A brief history of lung cancer screening

1950s: By mid-20th century, the causal association between tobacco exposure and lung cancer became clear and by the late 1950s attempts were made to develop a lung cancer screening strategy for high‐risk individuals, commonly with the combination of sputum cytology and chest x-ray.

1970s: The ACS recommended annual testing for current or former smokers with chest x-ray (and sometimes sputum cytology).

1980: The ACS withdrew the above recommendation for regular radiographic screening after randomized controlled trials failed to yield convincing evidence that such screening saved lives.

2013: After the National Lung Screening Trial found three annual LDCT screenings were associated with a 20% relative mortality reduction, compared with annual chest x-ray, the ACS issued a recommendation for annual screening with LDCT: in persons 55-74 years with a pack‐year history of 30 or more who currently smoke or formerly smoked but had not exceeded 15 years since quitting and had no life-limiting morbidity.
 

Future mortality

Although tobacco controls are expected to reduce age‐adjusted lung cancer mortality in the United States by 79% from 2015 to 2065, 4.4 million lung cancer deaths are projected to occur in this period, the authors stated. “A large fraction of these deaths can be prevented if we embrace the urgent challenge to improve our ability to identify the population at risk and apply our knowledge to achieve high rates of participation in regular [lung cancer screening].”

The study was funded by the American Cancer Society Guideline Development Group and the National Comprehensive Cancer Network. The authors disclosed no relevant competing interests. Dr. Golden and Dr. Didwania had no relevant conflicts of interest to declare with regard to their comments.

The American Cancer Society has updated its screening guidelines for lung cancer, the leading cause of cancer-specific deaths in the United States and the largest driver of potential years of life lost from cancer.

The 2023 screening guidance, aimed principally at reducing lung cancer mortality in asymptomatic but high-risk, tobacco-exposed individuals, expands the age eligibility and lowers both the former smoking history and the years since quitting threshold for screening with low-dose CT (LDCT).

It is based on the most recent evidence on the efficacy and effectiveness of screening and lung cancer risk in persons who formerly smoked, wrote the ACS’s Guideline Development Group led by Robert A. Smith, PhD, senior vice president of early cancer detection science. The new guidelines, which replace the 2013 statement, appear in CA: A Cancer Journal for Physicians.

The primary evidence source for the update was a systematic review of LDCT lung cancer screening conducted for the U.S. Preventive Services Task Force and published in 2021.

The new guideline continues a trend of expanding eligibility for lung cancer screening, which has had low uptake, to prevent more deaths. “Recent studies have shown that extending the age for persons who smoked and formerly smoked, eliminating the ‘years since quitting’ requirement, and lowering the pack-per-year recommendation could make a real difference in saving lives,” Dr. Smith said. “The relative risk of developing lung cancer in people who have smoked most of their life compared to people who never smoked is very high – about 70 times the risk.” Although lung cancer is the third most common malignancy in the United States, it accounts for more deaths than colorectal, breast, prostate, and cervical cancers combined.

The recommendation for annual LDCT for at-risk persons remains unchanged from 2013.

Among the 2023 eligibility changes:

• Age: Expanded to 50-80 years from 55-74 years.
• Smoking status: Changed to current or previous smoker from current smoker or smoker who quit within past 15 years (number of years since quitting no longer a criterion to start or stop screening). Dr. Smith noted that both the 2013 guidelines and other groups’ updated recommendations retained the eligibility cutoff of 15 years since smoking cessation. “But had their risk declined to a level that just did not justify continuing screening?” he asked. “There wasn’t an answer to that question, so we needed to look carefully at the absolute risk of lung cancer in persons who formerly smoked compared with people who currently smoked and people who never smoked.”
• Smoking history: Reduced to 20 or more pack-years (average of 20 cigarettes a day) versus 30 or more pack-years.
• Exclusions: Expanded to health conditions that may increase harm or hinder further evaluation, surgery, or treatment; comorbidities limiting life expectancy to fewer than 5 years; unwillingness to accept treatment for screen‐detected cancer, which was changed from 2013’s life‐limiting comorbid conditions, metallic implants or devices in the chest or back, home oxygen supplementation.

In addition, decision-making should be a shared process with a health professional providing the patient with information on the benefits, limitations, and harms of LDCT screening, as well as prescreening advice on smoking cessation and the offer of assistive counseling and pharmocotherapy.

“Overall, lung cancer screening remains one of the least used early cancer detection modalities in clinical practice. The new guidance opens up lung cancer screening to all former smokers regardless of time of cessation,” said internist William E. Golden, MD, MACP, a professor of medicine and public health at the University of Arkansas for Medical Sciences, Little Rock. “This may promote greater uptake in concert with greater availability of low-radiation CT scanning.”

While agreeing the expanded criteria will enfranchise nearly 5 million current and former U.S. smokers for screening and may reduce deaths, internist Aarati D. Didwania, MD, MMSCI, MACP, a professor of medicine and medical education at Northwestern University, Chicago, warned that increasing actual uptake may be an uphill battle. “The practical part of the equation is seeing that the scans get done. There is often a lag between a recommendation of a yearly test and getting insurance coverage for it, and many disadvantaged people face barriers.” Then there’s the knowledge gap. “Patients and doctors have to know what the new guidelines are and who has access,” she said.

Reaching the target population in rural areas is particularly challenging with the greater distances to imaging centers. Another barrier is that most electronic health records do not identify eligible patients based on smoking and pack‐year history.

In Dr. Didwania’s view, professional medical societies have an important role to play in educating their members, and through them, patients. “Disseminating information about the new recommendations is the first step and would be incredibly helpful.”
 

A brief history of lung cancer screening

1950s: By mid-20th century, the causal association between tobacco exposure and lung cancer became clear and by the late 1950s attempts were made to develop a lung cancer screening strategy for high‐risk individuals, commonly with the combination of sputum cytology and chest x-ray.

1970s: The ACS recommended annual testing for current or former smokers with chest x-ray (and sometimes sputum cytology).

1980: The ACS withdrew the above recommendation for regular radiographic screening after randomized controlled trials failed to yield convincing evidence that such screening saved lives.

2013: After the National Lung Screening Trial found three annual LDCT screenings were associated with a 20% relative mortality reduction, compared with annual chest x-ray, the ACS issued a recommendation for annual screening with LDCT: in persons 55-74 years with a pack‐year history of 30 or more who currently smoke or formerly smoked but had not exceeded 15 years since quitting and had no life-limiting morbidity.
 

Future mortality

Although tobacco controls are expected to reduce age‐adjusted lung cancer mortality in the United States by 79% from 2015 to 2065, 4.4 million lung cancer deaths are projected to occur in this period, the authors stated. “A large fraction of these deaths can be prevented if we embrace the urgent challenge to improve our ability to identify the population at risk and apply our knowledge to achieve high rates of participation in regular [lung cancer screening].”

The study was funded by the American Cancer Society Guideline Development Group and the National Comprehensive Cancer Network. The authors disclosed no relevant competing interests. Dr. Golden and Dr. Didwania had no relevant conflicts of interest to declare with regard to their comments.

This transcript has been edited for clarity.

I’ve been thinking lately about treatments after initial therapy for non–small cell lung cancers, what people often call second-line therapy.

I think the first thought is that, for all the regimens that are available and tested, the results are clearly not as good as seen with first-line therapy. I’ll get into some specifics in a second. That being the case, it’s really important to make the best choice for first-line therapy.

The second thing that is absolutely critical is to very carefully assess when that first-line therapy has stopped working and whether there is a need for a new systemic therapy. We very often have these situations where there is an oligoprogression, and by treating a single symptomatic lesion, you may get the patient in a very good place and may continue initial therapy. Very often, there is inconsequential growth of the cancer.

For example, if there is a 21% increase in the size of a primary tumor that is not associated with any symptoms in a person who is living their life and is not having any severe side effects, you have to think long and hard about changing that therapy. I wouldn’t even give a consolidative therapy there if they’re really doing well. Obviously, consolidative therapies are a new therapy, and they have their side effects with them as well.

Please think really carefully and weigh all factors, from the patient, the toxicity, and the benefit, before changing the initial systemic therapy. I would continue it as long as possible.

With second-line therapy, sadly, none of them have a huge benefit anywhere near what we see in first line. All the rates of response are well under 50%. Just getting into it, you’re not going to shrink the cancer by more than 30% in the majority of patients, so you have to think long and hard about making that switch.

Second, our standard still remains docetaxel, and the numbers on docetaxel are really not great. It’s about a 15% rate of response and a median survival of about 5 months. Now, by adding other RET drugs to docetaxel, you can achieve better results. By adding ramucirumab, for example, the response rate just about doubles and the duration of response and progression-free survival both go up by a few months.

For patients who have KRAS G12C, in the randomized trial that has been done so far, over docetaxel, you get, again, a doubling of response. For patients where response is important, you really double that response rate, but also you get an improvement in median progression-free survival by, again, 2-3 months. There is benefit there in terms of response and progression-free survival; however, it’s not huge.

Please remember, if you’re choosing to use docetaxel, to think about using alternative dosages and schedules. When you look at the course of a person treated with docetaxel over, let’s say, a 6-month period, you often see that doses are held. When you look at the total dose, it’s very similar to an every-2-week dose of a lower amount. I routinely give a 60-mg flat dose every 2 weeks.

I urge you to look at the progress of one of your patients over a 6-month period who was given the 75-mg dose. Many of those doses end up getting held. When all is said and done, you give a lower dose over that whole time from that 75-mg dose. Giving 35 mg/m² or a 60-mg flat dose every 2 weeks, you end up getting almost exactly the same amount of docetaxel. There’s really no convincing evidence that the higher dose is better. It’s clearly harder on the patient.

I’ve shared some thoughts about second-line therapy. We really have to do better. Please make sure that your first-line therapy is the best you can give. Make sure you’ve gotten everything out of that first-line therapy and that it will be continued as long as possible, as long as you and the patient have concluded that there’s benefit. When you do switch, try to give the most effective regimen that you have, which would be docetaxel with ramucirumab, or for patients with KRAS G12C, giving adagrasib or sotorasib at this point.

Dr. Kris is chief of the thoracic oncology service and the William and Joy Ruane Chair in Thoracic Oncology at Memorial Sloan Kettering Cancer Center in New York. He reported conflicts of interest with AstraZeneca, Roche/Genentech, Ariad Pharmaceuticals, Pfizer, and PUMA.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

I’ve been thinking lately about treatments after initial therapy for non–small cell lung cancers, what people often call second-line therapy.

I think the first thought is that, for all the regimens that are available and tested, the results are clearly not as good as seen with first-line therapy. I’ll get into some specifics in a second. That being the case, it’s really important to make the best choice for first-line therapy.

The second thing that is absolutely critical is to very carefully assess when that first-line therapy has stopped working and whether there is a need for a new systemic therapy. We very often have these situations where there is an oligoprogression, and by treating a single symptomatic lesion, you may get the patient in a very good place and may continue initial therapy. Very often, there is inconsequential growth of the cancer.

For example, if there is a 21% increase in the size of a primary tumor that is not associated with any symptoms in a person who is living their life and is not having any severe side effects, you have to think long and hard about changing that therapy. I wouldn’t even give a consolidative therapy there if they’re really doing well. Obviously, consolidative therapies are a new therapy, and they have their side effects with them as well.

Please think really carefully and weigh all factors, from the patient, the toxicity, and the benefit, before changing the initial systemic therapy. I would continue it as long as possible.

With second-line therapy, sadly, none of them have a huge benefit anywhere near what we see in first line. All the rates of response are well under 50%. Just getting into it, you’re not going to shrink the cancer by more than 30% in the majority of patients, so you have to think long and hard about making that switch.

Second, our standard still remains docetaxel, and the numbers on docetaxel are really not great. It’s about a 15% rate of response and a median survival of about 5 months. Now, by adding other RET drugs to docetaxel, you can achieve better results. By adding ramucirumab, for example, the response rate just about doubles and the duration of response and progression-free survival both go up by a few months.

For patients who have KRAS G12C, in the randomized trial that has been done so far, over docetaxel, you get, again, a doubling of response. For patients where response is important, you really double that response rate, but also you get an improvement in median progression-free survival by, again, 2-3 months. There is benefit there in terms of response and progression-free survival; however, it’s not huge.

Please remember, if you’re choosing to use docetaxel, to think about using alternative dosages and schedules. When you look at the course of a person treated with docetaxel over, let’s say, a 6-month period, you often see that doses are held. When you look at the total dose, it’s very similar to an every-2-week dose of a lower amount. I routinely give a 60-mg flat dose every 2 weeks.

I urge you to look at the progress of one of your patients over a 6-month period who was given the 75-mg dose. Many of those doses end up getting held. When all is said and done, you give a lower dose over that whole time from that 75-mg dose. Giving 35 mg/m² or a 60-mg flat dose every 2 weeks, you end up getting almost exactly the same amount of docetaxel. There’s really no convincing evidence that the higher dose is better. It’s clearly harder on the patient.

I’ve shared some thoughts about second-line therapy. We really have to do better. Please make sure that your first-line therapy is the best you can give. Make sure you’ve gotten everything out of that first-line therapy and that it will be continued as long as possible, as long as you and the patient have concluded that there’s benefit. When you do switch, try to give the most effective regimen that you have, which would be docetaxel with ramucirumab, or for patients with KRAS G12C, giving adagrasib or sotorasib at this point.

Dr. Kris is chief of the thoracic oncology service and the William and Joy Ruane Chair in Thoracic Oncology at Memorial Sloan Kettering Cancer Center in New York. He reported conflicts of interest with AstraZeneca, Roche/Genentech, Ariad Pharmaceuticals, Pfizer, and PUMA.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

I’ve been thinking lately about treatments after initial therapy for non–small cell lung cancers, what people often call second-line therapy.

I think the first thought is that, for all the regimens that are available and tested, the results are clearly not as good as seen with first-line therapy. I’ll get into some specifics in a second. That being the case, it’s really important to make the best choice for first-line therapy.

The second thing that is absolutely critical is to very carefully assess when that first-line therapy has stopped working and whether there is a need for a new systemic therapy. We very often have these situations where there is an oligoprogression, and by treating a single symptomatic lesion, you may get the patient in a very good place and may continue initial therapy. Very often, there is inconsequential growth of the cancer.

For example, if there is a 21% increase in the size of a primary tumor that is not associated with any symptoms in a person who is living their life and is not having any severe side effects, you have to think long and hard about changing that therapy. I wouldn’t even give a consolidative therapy there if they’re really doing well. Obviously, consolidative therapies are a new therapy, and they have their side effects with them as well.

Please think really carefully and weigh all factors, from the patient, the toxicity, and the benefit, before changing the initial systemic therapy. I would continue it as long as possible.

With second-line therapy, sadly, none of them have a huge benefit anywhere near what we see in first line. All the rates of response are well under 50%. Just getting into it, you’re not going to shrink the cancer by more than 30% in the majority of patients, so you have to think long and hard about making that switch.

Second, our standard still remains docetaxel, and the numbers on docetaxel are really not great. It’s about a 15% rate of response and a median survival of about 5 months. Now, by adding other RET drugs to docetaxel, you can achieve better results. By adding ramucirumab, for example, the response rate just about doubles and the duration of response and progression-free survival both go up by a few months.

For patients who have KRAS G12C, in the randomized trial that has been done so far, over docetaxel, you get, again, a doubling of response. For patients where response is important, you really double that response rate, but also you get an improvement in median progression-free survival by, again, 2-3 months. There is benefit there in terms of response and progression-free survival; however, it’s not huge.

Please remember, if you’re choosing to use docetaxel, to think about using alternative dosages and schedules. When you look at the course of a person treated with docetaxel over, let’s say, a 6-month period, you often see that doses are held. When you look at the total dose, it’s very similar to an every-2-week dose of a lower amount. I routinely give a 60-mg flat dose every 2 weeks.

I urge you to look at the progress of one of your patients over a 6-month period who was given the 75-mg dose. Many of those doses end up getting held. When all is said and done, you give a lower dose over that whole time from that 75-mg dose. Giving 35 mg/m² or a 60-mg flat dose every 2 weeks, you end up getting almost exactly the same amount of docetaxel. There’s really no convincing evidence that the higher dose is better. It’s clearly harder on the patient.

I’ve shared some thoughts about second-line therapy. We really have to do better. Please make sure that your first-line therapy is the best you can give. Make sure you’ve gotten everything out of that first-line therapy and that it will be continued as long as possible, as long as you and the patient have concluded that there’s benefit. When you do switch, try to give the most effective regimen that you have, which would be docetaxel with ramucirumab, or for patients with KRAS G12C, giving adagrasib or sotorasib at this point.

Dr. Kris is chief of the thoracic oncology service and the William and Joy Ruane Chair in Thoracic Oncology at Memorial Sloan Kettering Cancer Center in New York. He reported conflicts of interest with AstraZeneca, Roche/Genentech, Ariad Pharmaceuticals, Pfizer, and PUMA.

A version of this article first appeared on Medscape.com.

MADRID – Should patients with resectable non–small cell lung cancer (NSCLC) receive adjuvant therapy, neoadjuvant therapy, or both, experts asked during a special session at the European Society for Medical Oncology 2023 Congress.

Though immunotherapy is beneficial in resectable NSCLC, “we actually don’t know how much of the effect [is due to] the adjuvant and how much to the neoadjuvant therapy,” said Silke Gillessen, MD, head of the department of medical oncology, Università della Svizzera Italiana in Lugano, Switzerland.

Opening the session, Enriqueta Felip, MD, PhD, argued in favor of adjuvant therapy alone in resectable NSCLC.

Adjuvant immunotherapy after adjuvant chemotherapy is already considered standard of care for patients with resected NSCLC who don’t harbor EGFR and ALK mutations, explained Dr. Felip, head of the lung cancer unit at Vall d’Hebron University Hospital in Barcelona.

One major benefit to providing adjuvant therapy is that curative surgery won’t be delayed. Neoadjuvant therapy, on the other hand, leads about 15% of patients to forgo surgery, and about 30% who have both neoadjuvant therapy and surgery end up not receiving their planned adjuvant immunotherapy.

Another benefit: Emerging evidence suggests that the adjuvant-only option can improve disease-free and overall survival in select patients.

In the IMpower010 trial, for instance, adjuvant atezolizumab led to a marked improvement in disease-free survival, compared with best supportive care in patients with stage II-IIIA NSCLC. Patients with programmed death–ligand 1 expression of 50% or higher also demonstrated an overall survival benefit (hazard ratio, 0.42).

In the KEYNOTE-091 trial, adjuvant pembrolizumab significantly improved disease-free survival in all comers vs. placebo in patients with stage IB, II, or IIIA NSCLC who had surgery (HR, 0.76).

Providing adjuvant-only immunotherapy also allows for biomarker testing in resected specimens, Dr. Felip said, which may affect the choice of systemic therapy.

Next, Rafal Dziadziuszko, MD, PhD, argued in favor of neoadjuvant therapy alone in the setting of resectable NSCLC.

The advantages of providing treatment before surgery include initiating systemic treatment at an earlier point when most relapses are distant, possibly reducing the risk for tumor cell seeding during surgery as well as potentially leading to less invasive surgery by shrinking the tumors.

Dr. Dziadziuszko, from the Medical University of Gdansk in Poland, highlighted data from the Checkmate 816 trial, which showed that neoadjuvant nivolumab plus chemotherapy vs. chemotherapy alone increased the chance of having a pathologic complete response by nearly 14-fold in patients with IB-IIIA resectable NSCLC. Patients in the combination arm also demonstrated marked improvements in event-free survival, 31.6 months vs. 20.8 months, and overall survival.

The NADIM II trial, which coupled nivolumab and chemotherapy in stage III disease, found that neoadjuvant chemoimmunotherapy led to a pathologic complete response as well as a 52% improvement in progression-free survival and a 60% improvement in overall survival, compared with chemotherapy alone.

Despite these findings, several important questions remain, said Dr. Dziadziuszko. How many cycles of neoadjuvant immunochemotherapy should a patient receive before surgery? Will neoadjuvant therapy lead to treatment-related adverse events that preclude surgery? And for those who don’t have a strong response to neoadjuvant therapy, who should also receive adjuvant immunotherapy and for how long?

The latter question represents the “elephant in the room,” session chair Tony S. K. Mok, MD, chairman, department of clinical oncology, The Chinese University of Hong Kong.

With a paucity of overall survival data to provide a definitive answer, oncologists still face the age-old concern of “giving too much therapy in those who don’t need it” and “giving not enough therapy for those who need more,” said Dr. Mok.

Federico Cappuzzo, MD, PhD, argued that the key to patient selection for adjuvant therapy after neoadjuvant therapy and surgery lies in who has a pathologic complete response.

The current data suggest that patients receiving neoadjuvant therapy who achieve a pathologic complete response likely do not need adjuvant therapy whereas those who don’t achieve a complete response should receive adjuvant therapy, explained Dr. Cappuzzo, director of the department of oncology and hematology, AUSL della Romagna, Ravenna, Italy.

But, Dr. Mok asked, what about patients who achieve a major pathologic response in which the percentage of residual viable tumor is 10% or less or achieve less than a major pathologic response?

Dr. Mok suggested that measurable residual disease, which is indicative of recurrence, could potentially be used to determine the treatment pathway after neoadjuvant therapy and signal who may benefit from adjuvant therapy. However, he noted, studies evaluating the benefit of adjuvant therapy in this population would need to be done.

For patients who don’t respond well to neoadjuvant therapy and may benefit from adjuvant therapy, the question also becomes: “Do we give more of that same therapy?” asked Zofia Piotrowska, MD, a lung cancer medical oncologist at Massachusetts General Hospital Cancer Center, Boston, who was not involved in the debate.

“I think we really need to rethink that paradigm and try to develop new therapies that may work more effectively for those patients, to improve their outcomes,” Dr. Piotrowska said.

Dr. Mok declared relationships with a range of companies, including AstraZeneca, Boehringer Ingelheim, Pfizer, Novartis, SFJ Pharmaceuticals Roche, Merck Sharp & Dohme, and HutchMed. Dr. Felip declared relationships with AbbVie, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, F Hoffman–La Roche, Genentech, GlaxoSmithKline, Novartis, and others. Dr. Dziadziuszko declared relationships with Roche, AstraZeneca, Bristol-Myers Squibb, Takeda, Pfizer, Novartis, and others. Dr. Cappuzzo declared relationships with Roche, AstraZeneca, Bristol-Myers Squibb, Pfizer, Takeda, Lilly, Bayer, Amgen, Sanofi, and others.

A version of this article first appeared on Medscape.com.

MADRID – Should patients with resectable non–small cell lung cancer (NSCLC) receive adjuvant therapy, neoadjuvant therapy, or both, experts asked during a special session at the European Society for Medical Oncology 2023 Congress.

Though immunotherapy is beneficial in resectable NSCLC, “we actually don’t know how much of the effect [is due to] the adjuvant and how much to the neoadjuvant therapy,” said Silke Gillessen, MD, head of the department of medical oncology, Università della Svizzera Italiana in Lugano, Switzerland.

Opening the session, Enriqueta Felip, MD, PhD, argued in favor of adjuvant therapy alone in resectable NSCLC.

Adjuvant immunotherapy after adjuvant chemotherapy is already considered standard of care for patients with resected NSCLC who don’t harbor EGFR and ALK mutations, explained Dr. Felip, head of the lung cancer unit at Vall d’Hebron University Hospital in Barcelona.

One major benefit to providing adjuvant therapy is that curative surgery won’t be delayed. Neoadjuvant therapy, on the other hand, leads about 15% of patients to forgo surgery, and about 30% who have both neoadjuvant therapy and surgery end up not receiving their planned adjuvant immunotherapy.

Another benefit: Emerging evidence suggests that the adjuvant-only option can improve disease-free and overall survival in select patients.

In the IMpower010 trial, for instance, adjuvant atezolizumab led to a marked improvement in disease-free survival, compared with best supportive care in patients with stage II-IIIA NSCLC. Patients with programmed death–ligand 1 expression of 50% or higher also demonstrated an overall survival benefit (hazard ratio, 0.42).

In the KEYNOTE-091 trial, adjuvant pembrolizumab significantly improved disease-free survival in all comers vs. placebo in patients with stage IB, II, or IIIA NSCLC who had surgery (HR, 0.76).

Providing adjuvant-only immunotherapy also allows for biomarker testing in resected specimens, Dr. Felip said, which may affect the choice of systemic therapy.

Next, Rafal Dziadziuszko, MD, PhD, argued in favor of neoadjuvant therapy alone in the setting of resectable NSCLC.

The advantages of providing treatment before surgery include initiating systemic treatment at an earlier point when most relapses are distant, possibly reducing the risk for tumor cell seeding during surgery as well as potentially leading to less invasive surgery by shrinking the tumors.

Dr. Dziadziuszko, from the Medical University of Gdansk in Poland, highlighted data from the Checkmate 816 trial, which showed that neoadjuvant nivolumab plus chemotherapy vs. chemotherapy alone increased the chance of having a pathologic complete response by nearly 14-fold in patients with IB-IIIA resectable NSCLC. Patients in the combination arm also demonstrated marked improvements in event-free survival, 31.6 months vs. 20.8 months, and overall survival.

The NADIM II trial, which coupled nivolumab and chemotherapy in stage III disease, found that neoadjuvant chemoimmunotherapy led to a pathologic complete response as well as a 52% improvement in progression-free survival and a 60% improvement in overall survival, compared with chemotherapy alone.

Despite these findings, several important questions remain, said Dr. Dziadziuszko. How many cycles of neoadjuvant immunochemotherapy should a patient receive before surgery? Will neoadjuvant therapy lead to treatment-related adverse events that preclude surgery? And for those who don’t have a strong response to neoadjuvant therapy, who should also receive adjuvant immunotherapy and for how long?

The latter question represents the “elephant in the room,” session chair Tony S. K. Mok, MD, chairman, department of clinical oncology, The Chinese University of Hong Kong.

With a paucity of overall survival data to provide a definitive answer, oncologists still face the age-old concern of “giving too much therapy in those who don’t need it” and “giving not enough therapy for those who need more,” said Dr. Mok.

Federico Cappuzzo, MD, PhD, argued that the key to patient selection for adjuvant therapy after neoadjuvant therapy and surgery lies in who has a pathologic complete response.

The current data suggest that patients receiving neoadjuvant therapy who achieve a pathologic complete response likely do not need adjuvant therapy whereas those who don’t achieve a complete response should receive adjuvant therapy, explained Dr. Cappuzzo, director of the department of oncology and hematology, AUSL della Romagna, Ravenna, Italy.

But, Dr. Mok asked, what about patients who achieve a major pathologic response in which the percentage of residual viable tumor is 10% or less or achieve less than a major pathologic response?

Dr. Mok suggested that measurable residual disease, which is indicative of recurrence, could potentially be used to determine the treatment pathway after neoadjuvant therapy and signal who may benefit from adjuvant therapy. However, he noted, studies evaluating the benefit of adjuvant therapy in this population would need to be done.

For patients who don’t respond well to neoadjuvant therapy and may benefit from adjuvant therapy, the question also becomes: “Do we give more of that same therapy?” asked Zofia Piotrowska, MD, a lung cancer medical oncologist at Massachusetts General Hospital Cancer Center, Boston, who was not involved in the debate.

“I think we really need to rethink that paradigm and try to develop new therapies that may work more effectively for those patients, to improve their outcomes,” Dr. Piotrowska said.

Dr. Mok declared relationships with a range of companies, including AstraZeneca, Boehringer Ingelheim, Pfizer, Novartis, SFJ Pharmaceuticals Roche, Merck Sharp & Dohme, and HutchMed. Dr. Felip declared relationships with AbbVie, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, F Hoffman–La Roche, Genentech, GlaxoSmithKline, Novartis, and others. Dr. Dziadziuszko declared relationships with Roche, AstraZeneca, Bristol-Myers Squibb, Takeda, Pfizer, Novartis, and others. Dr. Cappuzzo declared relationships with Roche, AstraZeneca, Bristol-Myers Squibb, Pfizer, Takeda, Lilly, Bayer, Amgen, Sanofi, and others.

A version of this article first appeared on Medscape.com.

MADRID – Should patients with resectable non–small cell lung cancer (NSCLC) receive adjuvant therapy, neoadjuvant therapy, or both, experts asked during a special session at the European Society for Medical Oncology 2023 Congress.

Though immunotherapy is beneficial in resectable NSCLC, “we actually don’t know how much of the effect [is due to] the adjuvant and how much to the neoadjuvant therapy,” said Silke Gillessen, MD, head of the department of medical oncology, Università della Svizzera Italiana in Lugano, Switzerland.

Opening the session, Enriqueta Felip, MD, PhD, argued in favor of adjuvant therapy alone in resectable NSCLC.

Adjuvant immunotherapy after adjuvant chemotherapy is already considered standard of care for patients with resected NSCLC who don’t harbor EGFR and ALK mutations, explained Dr. Felip, head of the lung cancer unit at Vall d’Hebron University Hospital in Barcelona.

One major benefit to providing adjuvant therapy is that curative surgery won’t be delayed. Neoadjuvant therapy, on the other hand, leads about 15% of patients to forgo surgery, and about 30% who have both neoadjuvant therapy and surgery end up not receiving their planned adjuvant immunotherapy.

Another benefit: Emerging evidence suggests that the adjuvant-only option can improve disease-free and overall survival in select patients.

In the IMpower010 trial, for instance, adjuvant atezolizumab led to a marked improvement in disease-free survival, compared with best supportive care in patients with stage II-IIIA NSCLC. Patients with programmed death–ligand 1 expression of 50% or higher also demonstrated an overall survival benefit (hazard ratio, 0.42).

In the KEYNOTE-091 trial, adjuvant pembrolizumab significantly improved disease-free survival in all comers vs. placebo in patients with stage IB, II, or IIIA NSCLC who had surgery (HR, 0.76).

Providing adjuvant-only immunotherapy also allows for biomarker testing in resected specimens, Dr. Felip said, which may affect the choice of systemic therapy.

Next, Rafal Dziadziuszko, MD, PhD, argued in favor of neoadjuvant therapy alone in the setting of resectable NSCLC.

The advantages of providing treatment before surgery include initiating systemic treatment at an earlier point when most relapses are distant, possibly reducing the risk for tumor cell seeding during surgery as well as potentially leading to less invasive surgery by shrinking the tumors.

Dr. Dziadziuszko, from the Medical University of Gdansk in Poland, highlighted data from the Checkmate 816 trial, which showed that neoadjuvant nivolumab plus chemotherapy vs. chemotherapy alone increased the chance of having a pathologic complete response by nearly 14-fold in patients with IB-IIIA resectable NSCLC. Patients in the combination arm also demonstrated marked improvements in event-free survival, 31.6 months vs. 20.8 months, and overall survival.

The NADIM II trial, which coupled nivolumab and chemotherapy in stage III disease, found that neoadjuvant chemoimmunotherapy led to a pathologic complete response as well as a 52% improvement in progression-free survival and a 60% improvement in overall survival, compared with chemotherapy alone.

Despite these findings, several important questions remain, said Dr. Dziadziuszko. How many cycles of neoadjuvant immunochemotherapy should a patient receive before surgery? Will neoadjuvant therapy lead to treatment-related adverse events that preclude surgery? And for those who don’t have a strong response to neoadjuvant therapy, who should also receive adjuvant immunotherapy and for how long?

The latter question represents the “elephant in the room,” session chair Tony S. K. Mok, MD, chairman, department of clinical oncology, The Chinese University of Hong Kong.

With a paucity of overall survival data to provide a definitive answer, oncologists still face the age-old concern of “giving too much therapy in those who don’t need it” and “giving not enough therapy for those who need more,” said Dr. Mok.

Federico Cappuzzo, MD, PhD, argued that the key to patient selection for adjuvant therapy after neoadjuvant therapy and surgery lies in who has a pathologic complete response.

The current data suggest that patients receiving neoadjuvant therapy who achieve a pathologic complete response likely do not need adjuvant therapy whereas those who don’t achieve a complete response should receive adjuvant therapy, explained Dr. Cappuzzo, director of the department of oncology and hematology, AUSL della Romagna, Ravenna, Italy.

But, Dr. Mok asked, what about patients who achieve a major pathologic response in which the percentage of residual viable tumor is 10% or less or achieve less than a major pathologic response?

Dr. Mok suggested that measurable residual disease, which is indicative of recurrence, could potentially be used to determine the treatment pathway after neoadjuvant therapy and signal who may benefit from adjuvant therapy. However, he noted, studies evaluating the benefit of adjuvant therapy in this population would need to be done.

For patients who don’t respond well to neoadjuvant therapy and may benefit from adjuvant therapy, the question also becomes: “Do we give more of that same therapy?” asked Zofia Piotrowska, MD, a lung cancer medical oncologist at Massachusetts General Hospital Cancer Center, Boston, who was not involved in the debate.

“I think we really need to rethink that paradigm and try to develop new therapies that may work more effectively for those patients, to improve their outcomes,” Dr. Piotrowska said.

Dr. Mok declared relationships with a range of companies, including AstraZeneca, Boehringer Ingelheim, Pfizer, Novartis, SFJ Pharmaceuticals Roche, Merck Sharp & Dohme, and HutchMed. Dr. Felip declared relationships with AbbVie, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, F Hoffman–La Roche, Genentech, GlaxoSmithKline, Novartis, and others. Dr. Dziadziuszko declared relationships with Roche, AstraZeneca, Bristol-Myers Squibb, Takeda, Pfizer, Novartis, and others. Dr. Cappuzzo declared relationships with Roche, AstraZeneca, Bristol-Myers Squibb, Pfizer, Takeda, Lilly, Bayer, Amgen, Sanofi, and others.

A version of this article first appeared on Medscape.com.

MADRID – New data from three trials evaluating the bispecific antibody amivantamab (Rybrevant) in EGFR-mutated advanced non–small cell lung cancer (NSCLC) have revealed a clear benefit, experts said at the annual meeting of the European Society for Medical Oncology (ESMO).

The results of the three trials – PAPILLON, MARIPOSA, and MARIPOSA-2 – are “really exciting” for patients harboring EGFR mutations, said Silke Gillessen, MD, head of the department of medical oncology, Università della Svizzera Italiana in Lugano, Switzerland, and the ESMO 2023 scientific chair.

Presenting findings from PAPILLON, Nicolas Girard, MD, PhD, highlighted outcomes among patients with EGFR exon 20 insertion-mutated advanced NSCLC. These patients, who represent about 2%-3% of NSCLC cases, have “historically poor” outcomes, with a 5-year overall survival rate of just 8%.

Tumors harboring exon 20 insertions are largely insensitive to targeted and immune checkpoint therapies, explained Dr. Girard, from Curie-Montsouris Thorax Institute, Institut Curie, Paris. That leaves platinum-based chemotherapy as the standard of care, which has “limited efficacy,” he noted.

The FDA approved amivantamab in 2021 for EGFR exon 20 insertion-mutated advanced NSCLC after progression on platinum-based chemotherapy, but the PAPILLON trial explored whether combining the two therapies upfront would provide a more meaningful benefit.

In the trial, 308 treatment-naive patients with locally advanced or metastatic NSCLC and documented exon 20 insertions were randomly assigned to amivantamab plus chemotherapy or chemotherapy alone. The median age was about 62 years, approximately half were female, and just over 60% were Asian – a similar patient profile as MARIPOSA and MARIPOSA-2.

The results, simultaneously published in The New England Journal of Medicine, showed that amivantamab plus chemotherapy significantly increased progression-free survival (PFS). More specifically, after a median follow-up of 14.9 months, patients receiving the combination had a median PFS of 11.4 months vs. 5.7 months with chemotherapy alone (hazard ratio, 0.395; P < .0001). This benefit consistently occurred across predefined subgroups.

Amivantamab plus chemotherapy was associated with a lower risk of a second progression, with the median not reached vs. 17.2 months with chemotherapy alone (HR, 0.493; P = .001).

A higher proportion of patients receiving the combination had an objective response – 73% vs. 47% – and these patients had a longer duration of response as well – 9.7 months vs. 4.4 months.

The overall survival data were immature but showed a trend toward a reduced risk of death for those on the combination (HR, 0.675; P = .106).

The rates of grade ≥ 3 adverse events were 75% with amivantamab plus chemotherapy and 54% with chemotherapy alone, and adverse events leading to discontinuation of amivantamab occurred in 7% of patients. Pneumonitis/interstitial lung disease (ILD) was reported in 3% of patients in the combination therapy arm.

Dr. Girard concluded that, with a safety profile “consistent” with that seen for the individual agents, amivantamab plus chemotherapy “represents a new standard of care” for first-line treatment of EGFR exon 20 insertion-mutated advanced NSCLC.

Benjamin Besse, MD, PhD, who was not involved in the research, agreed that this combination is “definitely a new standard of care.”

The effect of giving amivantamab alongside chemotherapy “seems to be really additive,” said Dr. Besse, director of clinical research at the Gustave Roussy Institute and professor of medical oncology at Paris-Saclay University, both in Paris. But he noted that amivantamab is a “challenging drug in terms of toxicity.”
 

The MARIPOSA trials

The two MARIPOSA trials also demonstrated that amivantamab, in combination with other agents, improved PFS among patients with EGFR-mutated advanced NSCLC.

Byoung Chul Cho, MD, PhD, Yonsei Cancer Center, Seoul, South Korea, presented results from MARIPOSA, which focused on patients with any kind of EGFR mutation.

Although the EGFR tyrosine kinase inhibitor (TKI) osimertinib is the current standard of care in this first-line setting, “resistance and disease progression are nearly inevitable,” and secondary EGFR and MET mutations may account for up to 50% of tumor resistance, Dr. Cho noted.

Early clinical data suggest that combining amivantamab with the highly selective third-generation EGFR TKI lazertinib leads to clinical activity and durable responses.

For the phase 3 MARIPOSA trial, 1,074 patients with treatment-naive locally advanced or metastatic EGFR-mutant NSCLC were randomly assigned to amivantamab plus lazertinib (n = 429), osimertinib alone (n = 429), or lazertinib alone (n = 216).

After a median follow-up of 22 months, the median PFS among patients on the combination was 23.7 months vs. 16.6 months for those on osimertinib alone (HR, 0.70; P < .001) and 18.5 months for those on lazertinib alone.

The PFS benefit observed with amivantamab plus lazertinib occurred across subgroups, including among patients with brain metastases. The combination reduced the risk for extracranial progression or death by 32% and improved median PFS by 9 months, compared with osimertinib alone (HR, 0.68; P < .001).

The risk for a second progression was also lower with the combination (HR, 0.75).

Interim overall survival data suggested a benefit with the combination therapy, compared with osimertinib alone (HR, 0.80; P = .11).

Grade 3 or higher adverse events were more common among patients treated with the combination vs. osimertinib alone – 75% vs. 43%. Higher rates of treatment-related discontinuation of any agent were observed in the combination group – 35% vs. 14% – though rates of adverse events leading to death were similar between the groups – 8% and 7%, respectively.

As in PAPILLON, rates of ILD/pneumonitis were “low,” said Dr. Cho, at approximately 3% in both treatment arms. However, he noted, rates of venous thromboembolism were higher with the combination, with grade ≥ 3 events occurring in 11% vs. 3.7% of patients on osimertinib.

Based on the findings, amivantamab plus lazertinib “represents a new standard of care in first-line EGFR-mutant advanced NSCLC,” Dr. Cho said. “It has been a long way and we finally made it.”

Next up is MARIPOSA-2, which evaluated patients with EGFR-mutated locally advanced or metastatic NSCLC who had progressed on or after osimertinib.

In this trial, 657 patients were randomly assigned to amivantamab plus lazertinib and chemotherapy (n = 263), amivantamab plus chemotherapy (n = 263), or chemotherapy alone (n = 131).

Given the increased risk for hematologic toxicities, the study protocol was adjusted in the triple therapy arm so that patients received lazertinib after completing carboplatin.

The findings, presented by study investigator Antonio Passaro, MD, PhD, were simultaneously published in Annals of Oncology.

After a median follow-up of 8.7 months, the triple therapy reduced the risk for progression or death by 56% (HR,0.44) and amivantamab plus chemotherapy reduced the risk for progression or death by 52% (HR, 0.48). Overall, the median PFS was 8.3 months in the triple combination arm, 6.3 months in the amivantamab plus chemotherapy arm, and 4.2 months in the chemotherapy arm.

This PFS benefit was observed across prespecified subgroups with both combination therapies. The combinations also reduced the risk for intracranial progression (HR, 0.58 in the triple therapy arm; HR, 0.55 in the amivantamab plus chemotherapy arm).

The current interim analysis did not show an overall survival benefit with either combination therapy vs. chemotherapy alone, although the survival curve hinted at a benefit in the amivantamab plus chemotherapy arm.

The median duration of response was 9.4 months for triple therapy, 6.9 months for the double combination, and 5.6 months for monotherapy.

Rates of grade ≥ 3 adverse events were notably higher in the combination groups – 92% of patients on triple therapy, 72% on double, and 48% on chemotherapy alone. But the treatment duration was longer in the combination groups and adverse events leading to death were low, as was discontinuation.

Amivantamab plus chemotherapy or plus lazertinib and chemotherapy are the “first regimens to demonstrate improved PFS vs. chemotherapy in EGFR-mutated NSCLC after disease progression on osimertinib,” concluded Dr. Passaro, from the European Institute of Oncology IRCCS, Milan, who presented the findings.

Dr. Passaro added that, given the consistent efficacy and more favorable safety profile, “we can say that amivantamab plus chemotherapy is the new standard of care for patients that are progressing after osimertinib,” although more follow-up is required to understand its “real impact” in the clinic.

Zofia Piotrowska, MD, who was not involved in either MARIPOSA trial, said both “are really important” in the EGFR-mutant NSCLC space.

The studies “addressed two different questions,” but both were “positive, and I think clinically significantly,” said Dr. Piotrowska, a lung cancer specialist at Massachusetts General Hospital Cancer Center, Boston.

However, Dr. Piotrowska noted that a core question for the community will be “how we find that balance between the clinical benefits [and] the toxicities.”

“There’s not going to be one easy answer” and treatment selection will have to be made on a “patient-by-patient basis,” she said.

PAPILLON, MARIPOSA, and MARIPOSA-2 were funded by Janssen Pharmaceuticals. Dr. Girard declared relationships with AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Hoffmann La Roche, Lilly, Merck Sharp Dohme, Novartis, Pfizer, and others. Dr. Cho declared relationships with Novartis, AstraZeneca, Boehringer-Ingelheim, Roche, BMS, Onegene Biotechnology, Pfizer, Eli Lilly, and others. Dr. Passaro declared relationships with AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Janssen, Pfizer, Roche, Bayer, Boehringer-Ingelheim, Merck Sharp & Dohme, Mundipharma, Daiichi Sankyo, Medscape, and eCancer. Dr. Besse declared institutional relationships with AbbVie, Amgen, AstraZeneca, BeiGene, Blueprint Medicines, Daiichi-Sankyo, Eli Lilly, EISAI, Genzyme Corporation, GSK, and others. Dr. Piotrowska declared relationships with numerous companies including AstraZeneca, Novartis, and Takeda.

A version of this article first appeared on Medscape.com.

MADRID – New data from three trials evaluating the bispecific antibody amivantamab (Rybrevant) in EGFR-mutated advanced non–small cell lung cancer (NSCLC) have revealed a clear benefit, experts said at the annual meeting of the European Society for Medical Oncology (ESMO).

The results of the three trials – PAPILLON, MARIPOSA, and MARIPOSA-2 – are “really exciting” for patients harboring EGFR mutations, said Silke Gillessen, MD, head of the department of medical oncology, Università della Svizzera Italiana in Lugano, Switzerland, and the ESMO 2023 scientific chair.

Presenting findings from PAPILLON, Nicolas Girard, MD, PhD, highlighted outcomes among patients with EGFR exon 20 insertion-mutated advanced NSCLC. These patients, who represent about 2%-3% of NSCLC cases, have “historically poor” outcomes, with a 5-year overall survival rate of just 8%.

Tumors harboring exon 20 insertions are largely insensitive to targeted and immune checkpoint therapies, explained Dr. Girard, from Curie-Montsouris Thorax Institute, Institut Curie, Paris. That leaves platinum-based chemotherapy as the standard of care, which has “limited efficacy,” he noted.

The FDA approved amivantamab in 2021 for EGFR exon 20 insertion-mutated advanced NSCLC after progression on platinum-based chemotherapy, but the PAPILLON trial explored whether combining the two therapies upfront would provide a more meaningful benefit.

In the trial, 308 treatment-naive patients with locally advanced or metastatic NSCLC and documented exon 20 insertions were randomly assigned to amivantamab plus chemotherapy or chemotherapy alone. The median age was about 62 years, approximately half were female, and just over 60% were Asian – a similar patient profile as MARIPOSA and MARIPOSA-2.

The results, simultaneously published in The New England Journal of Medicine, showed that amivantamab plus chemotherapy significantly increased progression-free survival (PFS). More specifically, after a median follow-up of 14.9 months, patients receiving the combination had a median PFS of 11.4 months vs. 5.7 months with chemotherapy alone (hazard ratio, 0.395; P < .0001). This benefit consistently occurred across predefined subgroups.

Amivantamab plus chemotherapy was associated with a lower risk of a second progression, with the median not reached vs. 17.2 months with chemotherapy alone (HR, 0.493; P = .001).

A higher proportion of patients receiving the combination had an objective response – 73% vs. 47% – and these patients had a longer duration of response as well – 9.7 months vs. 4.4 months.

The overall survival data were immature but showed a trend toward a reduced risk of death for those on the combination (HR, 0.675; P = .106).

The rates of grade ≥ 3 adverse events were 75% with amivantamab plus chemotherapy and 54% with chemotherapy alone, and adverse events leading to discontinuation of amivantamab occurred in 7% of patients. Pneumonitis/interstitial lung disease (ILD) was reported in 3% of patients in the combination therapy arm.

Dr. Girard concluded that, with a safety profile “consistent” with that seen for the individual agents, amivantamab plus chemotherapy “represents a new standard of care” for first-line treatment of EGFR exon 20 insertion-mutated advanced NSCLC.

Benjamin Besse, MD, PhD, who was not involved in the research, agreed that this combination is “definitely a new standard of care.”

The effect of giving amivantamab alongside chemotherapy “seems to be really additive,” said Dr. Besse, director of clinical research at the Gustave Roussy Institute and professor of medical oncology at Paris-Saclay University, both in Paris. But he noted that amivantamab is a “challenging drug in terms of toxicity.”
 

The MARIPOSA trials

The two MARIPOSA trials also demonstrated that amivantamab, in combination with other agents, improved PFS among patients with EGFR-mutated advanced NSCLC.

Byoung Chul Cho, MD, PhD, Yonsei Cancer Center, Seoul, South Korea, presented results from MARIPOSA, which focused on patients with any kind of EGFR mutation.

Although the EGFR tyrosine kinase inhibitor (TKI) osimertinib is the current standard of care in this first-line setting, “resistance and disease progression are nearly inevitable,” and secondary EGFR and MET mutations may account for up to 50% of tumor resistance, Dr. Cho noted.

Early clinical data suggest that combining amivantamab with the highly selective third-generation EGFR TKI lazertinib leads to clinical activity and durable responses.

For the phase 3 MARIPOSA trial, 1,074 patients with treatment-naive locally advanced or metastatic EGFR-mutant NSCLC were randomly assigned to amivantamab plus lazertinib (n = 429), osimertinib alone (n = 429), or lazertinib alone (n = 216).

After a median follow-up of 22 months, the median PFS among patients on the combination was 23.7 months vs. 16.6 months for those on osimertinib alone (HR, 0.70; P < .001) and 18.5 months for those on lazertinib alone.

The PFS benefit observed with amivantamab plus lazertinib occurred across subgroups, including among patients with brain metastases. The combination reduced the risk for extracranial progression or death by 32% and improved median PFS by 9 months, compared with osimertinib alone (HR, 0.68; P < .001).

The risk for a second progression was also lower with the combination (HR, 0.75).

Interim overall survival data suggested a benefit with the combination therapy, compared with osimertinib alone (HR, 0.80; P = .11).

Grade 3 or higher adverse events were more common among patients treated with the combination vs. osimertinib alone – 75% vs. 43%. Higher rates of treatment-related discontinuation of any agent were observed in the combination group – 35% vs. 14% – though rates of adverse events leading to death were similar between the groups – 8% and 7%, respectively.

As in PAPILLON, rates of ILD/pneumonitis were “low,” said Dr. Cho, at approximately 3% in both treatment arms. However, he noted, rates of venous thromboembolism were higher with the combination, with grade ≥ 3 events occurring in 11% vs. 3.7% of patients on osimertinib.

Based on the findings, amivantamab plus lazertinib “represents a new standard of care in first-line EGFR-mutant advanced NSCLC,” Dr. Cho said. “It has been a long way and we finally made it.”

Next up is MARIPOSA-2, which evaluated patients with EGFR-mutated locally advanced or metastatic NSCLC who had progressed on or after osimertinib.

In this trial, 657 patients were randomly assigned to amivantamab plus lazertinib and chemotherapy (n = 263), amivantamab plus chemotherapy (n = 263), or chemotherapy alone (n = 131).

Given the increased risk for hematologic toxicities, the study protocol was adjusted in the triple therapy arm so that patients received lazertinib after completing carboplatin.

The findings, presented by study investigator Antonio Passaro, MD, PhD, were simultaneously published in Annals of Oncology.

After a median follow-up of 8.7 months, the triple therapy reduced the risk for progression or death by 56% (HR,0.44) and amivantamab plus chemotherapy reduced the risk for progression or death by 52% (HR, 0.48). Overall, the median PFS was 8.3 months in the triple combination arm, 6.3 months in the amivantamab plus chemotherapy arm, and 4.2 months in the chemotherapy arm.

This PFS benefit was observed across prespecified subgroups with both combination therapies. The combinations also reduced the risk for intracranial progression (HR, 0.58 in the triple therapy arm; HR, 0.55 in the amivantamab plus chemotherapy arm).

The current interim analysis did not show an overall survival benefit with either combination therapy vs. chemotherapy alone, although the survival curve hinted at a benefit in the amivantamab plus chemotherapy arm.

The median duration of response was 9.4 months for triple therapy, 6.9 months for the double combination, and 5.6 months for monotherapy.

Rates of grade ≥ 3 adverse events were notably higher in the combination groups – 92% of patients on triple therapy, 72% on double, and 48% on chemotherapy alone. But the treatment duration was longer in the combination groups and adverse events leading to death were low, as was discontinuation.

Amivantamab plus chemotherapy or plus lazertinib and chemotherapy are the “first regimens to demonstrate improved PFS vs. chemotherapy in EGFR-mutated NSCLC after disease progression on osimertinib,” concluded Dr. Passaro, from the European Institute of Oncology IRCCS, Milan, who presented the findings.

Dr. Passaro added that, given the consistent efficacy and more favorable safety profile, “we can say that amivantamab plus chemotherapy is the new standard of care for patients that are progressing after osimertinib,” although more follow-up is required to understand its “real impact” in the clinic.

Zofia Piotrowska, MD, who was not involved in either MARIPOSA trial, said both “are really important” in the EGFR-mutant NSCLC space.

The studies “addressed two different questions,” but both were “positive, and I think clinically significantly,” said Dr. Piotrowska, a lung cancer specialist at Massachusetts General Hospital Cancer Center, Boston.

However, Dr. Piotrowska noted that a core question for the community will be “how we find that balance between the clinical benefits [and] the toxicities.”

“There’s not going to be one easy answer” and treatment selection will have to be made on a “patient-by-patient basis,” she said.

PAPILLON, MARIPOSA, and MARIPOSA-2 were funded by Janssen Pharmaceuticals. Dr. Girard declared relationships with AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Hoffmann La Roche, Lilly, Merck Sharp Dohme, Novartis, Pfizer, and others. Dr. Cho declared relationships with Novartis, AstraZeneca, Boehringer-Ingelheim, Roche, BMS, Onegene Biotechnology, Pfizer, Eli Lilly, and others. Dr. Passaro declared relationships with AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Janssen, Pfizer, Roche, Bayer, Boehringer-Ingelheim, Merck Sharp & Dohme, Mundipharma, Daiichi Sankyo, Medscape, and eCancer. Dr. Besse declared institutional relationships with AbbVie, Amgen, AstraZeneca, BeiGene, Blueprint Medicines, Daiichi-Sankyo, Eli Lilly, EISAI, Genzyme Corporation, GSK, and others. Dr. Piotrowska declared relationships with numerous companies including AstraZeneca, Novartis, and Takeda.

A version of this article first appeared on Medscape.com.

MADRID – New data from three trials evaluating the bispecific antibody amivantamab (Rybrevant) in EGFR-mutated advanced non–small cell lung cancer (NSCLC) have revealed a clear benefit, experts said at the annual meeting of the European Society for Medical Oncology (ESMO).

The results of the three trials – PAPILLON, MARIPOSA, and MARIPOSA-2 – are “really exciting” for patients harboring EGFR mutations, said Silke Gillessen, MD, head of the department of medical oncology, Università della Svizzera Italiana in Lugano, Switzerland, and the ESMO 2023 scientific chair.

Presenting findings from PAPILLON, Nicolas Girard, MD, PhD, highlighted outcomes among patients with EGFR exon 20 insertion-mutated advanced NSCLC. These patients, who represent about 2%-3% of NSCLC cases, have “historically poor” outcomes, with a 5-year overall survival rate of just 8%.

Tumors harboring exon 20 insertions are largely insensitive to targeted and immune checkpoint therapies, explained Dr. Girard, from Curie-Montsouris Thorax Institute, Institut Curie, Paris. That leaves platinum-based chemotherapy as the standard of care, which has “limited efficacy,” he noted.

The FDA approved amivantamab in 2021 for EGFR exon 20 insertion-mutated advanced NSCLC after progression on platinum-based chemotherapy, but the PAPILLON trial explored whether combining the two therapies upfront would provide a more meaningful benefit.

In the trial, 308 treatment-naive patients with locally advanced or metastatic NSCLC and documented exon 20 insertions were randomly assigned to amivantamab plus chemotherapy or chemotherapy alone. The median age was about 62 years, approximately half were female, and just over 60% were Asian – a similar patient profile as MARIPOSA and MARIPOSA-2.

The results, simultaneously published in The New England Journal of Medicine, showed that amivantamab plus chemotherapy significantly increased progression-free survival (PFS). More specifically, after a median follow-up of 14.9 months, patients receiving the combination had a median PFS of 11.4 months vs. 5.7 months with chemotherapy alone (hazard ratio, 0.395; P < .0001). This benefit consistently occurred across predefined subgroups.

Amivantamab plus chemotherapy was associated with a lower risk of a second progression, with the median not reached vs. 17.2 months with chemotherapy alone (HR, 0.493; P = .001).

A higher proportion of patients receiving the combination had an objective response – 73% vs. 47% – and these patients had a longer duration of response as well – 9.7 months vs. 4.4 months.

The overall survival data were immature but showed a trend toward a reduced risk of death for those on the combination (HR, 0.675; P = .106).

The rates of grade ≥ 3 adverse events were 75% with amivantamab plus chemotherapy and 54% with chemotherapy alone, and adverse events leading to discontinuation of amivantamab occurred in 7% of patients. Pneumonitis/interstitial lung disease (ILD) was reported in 3% of patients in the combination therapy arm.

Dr. Girard concluded that, with a safety profile “consistent” with that seen for the individual agents, amivantamab plus chemotherapy “represents a new standard of care” for first-line treatment of EGFR exon 20 insertion-mutated advanced NSCLC.

Benjamin Besse, MD, PhD, who was not involved in the research, agreed that this combination is “definitely a new standard of care.”

The effect of giving amivantamab alongside chemotherapy “seems to be really additive,” said Dr. Besse, director of clinical research at the Gustave Roussy Institute and professor of medical oncology at Paris-Saclay University, both in Paris. But he noted that amivantamab is a “challenging drug in terms of toxicity.”
 

The MARIPOSA trials

The two MARIPOSA trials also demonstrated that amivantamab, in combination with other agents, improved PFS among patients with EGFR-mutated advanced NSCLC.

Byoung Chul Cho, MD, PhD, Yonsei Cancer Center, Seoul, South Korea, presented results from MARIPOSA, which focused on patients with any kind of EGFR mutation.

Although the EGFR tyrosine kinase inhibitor (TKI) osimertinib is the current standard of care in this first-line setting, “resistance and disease progression are nearly inevitable,” and secondary EGFR and MET mutations may account for up to 50% of tumor resistance, Dr. Cho noted.

Early clinical data suggest that combining amivantamab with the highly selective third-generation EGFR TKI lazertinib leads to clinical activity and durable responses.

For the phase 3 MARIPOSA trial, 1,074 patients with treatment-naive locally advanced or metastatic EGFR-mutant NSCLC were randomly assigned to amivantamab plus lazertinib (n = 429), osimertinib alone (n = 429), or lazertinib alone (n = 216).

After a median follow-up of 22 months, the median PFS among patients on the combination was 23.7 months vs. 16.6 months for those on osimertinib alone (HR, 0.70; P < .001) and 18.5 months for those on lazertinib alone.

The PFS benefit observed with amivantamab plus lazertinib occurred across subgroups, including among patients with brain metastases. The combination reduced the risk for extracranial progression or death by 32% and improved median PFS by 9 months, compared with osimertinib alone (HR, 0.68; P < .001).

The risk for a second progression was also lower with the combination (HR, 0.75).

Interim overall survival data suggested a benefit with the combination therapy, compared with osimertinib alone (HR, 0.80; P = .11).

Grade 3 or higher adverse events were more common among patients treated with the combination vs. osimertinib alone – 75% vs. 43%. Higher rates of treatment-related discontinuation of any agent were observed in the combination group – 35% vs. 14% – though rates of adverse events leading to death were similar between the groups – 8% and 7%, respectively.

As in PAPILLON, rates of ILD/pneumonitis were “low,” said Dr. Cho, at approximately 3% in both treatment arms. However, he noted, rates of venous thromboembolism were higher with the combination, with grade ≥ 3 events occurring in 11% vs. 3.7% of patients on osimertinib.

Based on the findings, amivantamab plus lazertinib “represents a new standard of care in first-line EGFR-mutant advanced NSCLC,” Dr. Cho said. “It has been a long way and we finally made it.”

Next up is MARIPOSA-2, which evaluated patients with EGFR-mutated locally advanced or metastatic NSCLC who had progressed on or after osimertinib.

In this trial, 657 patients were randomly assigned to amivantamab plus lazertinib and chemotherapy (n = 263), amivantamab plus chemotherapy (n = 263), or chemotherapy alone (n = 131).

Given the increased risk for hematologic toxicities, the study protocol was adjusted in the triple therapy arm so that patients received lazertinib after completing carboplatin.

The findings, presented by study investigator Antonio Passaro, MD, PhD, were simultaneously published in Annals of Oncology.

After a median follow-up of 8.7 months, the triple therapy reduced the risk for progression or death by 56% (HR,0.44) and amivantamab plus chemotherapy reduced the risk for progression or death by 52% (HR, 0.48). Overall, the median PFS was 8.3 months in the triple combination arm, 6.3 months in the amivantamab plus chemotherapy arm, and 4.2 months in the chemotherapy arm.

This PFS benefit was observed across prespecified subgroups with both combination therapies. The combinations also reduced the risk for intracranial progression (HR, 0.58 in the triple therapy arm; HR, 0.55 in the amivantamab plus chemotherapy arm).

The current interim analysis did not show an overall survival benefit with either combination therapy vs. chemotherapy alone, although the survival curve hinted at a benefit in the amivantamab plus chemotherapy arm.

The median duration of response was 9.4 months for triple therapy, 6.9 months for the double combination, and 5.6 months for monotherapy.

Rates of grade ≥ 3 adverse events were notably higher in the combination groups – 92% of patients on triple therapy, 72% on double, and 48% on chemotherapy alone. But the treatment duration was longer in the combination groups and adverse events leading to death were low, as was discontinuation.

Amivantamab plus chemotherapy or plus lazertinib and chemotherapy are the “first regimens to demonstrate improved PFS vs. chemotherapy in EGFR-mutated NSCLC after disease progression on osimertinib,” concluded Dr. Passaro, from the European Institute of Oncology IRCCS, Milan, who presented the findings.

Dr. Passaro added that, given the consistent efficacy and more favorable safety profile, “we can say that amivantamab plus chemotherapy is the new standard of care for patients that are progressing after osimertinib,” although more follow-up is required to understand its “real impact” in the clinic.

Zofia Piotrowska, MD, who was not involved in either MARIPOSA trial, said both “are really important” in the EGFR-mutant NSCLC space.

The studies “addressed two different questions,” but both were “positive, and I think clinically significantly,” said Dr. Piotrowska, a lung cancer specialist at Massachusetts General Hospital Cancer Center, Boston.

However, Dr. Piotrowska noted that a core question for the community will be “how we find that balance between the clinical benefits [and] the toxicities.”

“There’s not going to be one easy answer” and treatment selection will have to be made on a “patient-by-patient basis,” she said.

PAPILLON, MARIPOSA, and MARIPOSA-2 were funded by Janssen Pharmaceuticals. Dr. Girard declared relationships with AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Hoffmann La Roche, Lilly, Merck Sharp Dohme, Novartis, Pfizer, and others. Dr. Cho declared relationships with Novartis, AstraZeneca, Boehringer-Ingelheim, Roche, BMS, Onegene Biotechnology, Pfizer, Eli Lilly, and others. Dr. Passaro declared relationships with AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Janssen, Pfizer, Roche, Bayer, Boehringer-Ingelheim, Merck Sharp & Dohme, Mundipharma, Daiichi Sankyo, Medscape, and eCancer. Dr. Besse declared institutional relationships with AbbVie, Amgen, AstraZeneca, BeiGene, Blueprint Medicines, Daiichi-Sankyo, Eli Lilly, EISAI, Genzyme Corporation, GSK, and others. Dr. Piotrowska declared relationships with numerous companies including AstraZeneca, Novartis, and Takeda.

A version of this article first appeared on Medscape.com.

Black Americans attempt to quit smoking more often than their White counterparts but are less likely to succeed, and they pay the health consequences.

This knowledge has driven Kevin Choi, MD, acting scientific director of the National Institute on Minority Health and Health Disparities in Bethesda, Md., to dedicate his career to studying the patterns and disparities of smoking among these patients.

Dr. Choi wants primary care clinicians to know not just that they have the potential to educate patients on the harms of smoking – most patients already know smoking is unhealthy – but that aiding them will likely necessitate more assertive follow-up.

To do so, “we need to understand the bigger backdrop of racial and sociological stress experienced by the Black population, which stems from both interpersonal and structural racism,” Dr. Choi said.

Not only are Black smokers more likely to try to quit, but they also tend to smoke fewer cigarettes per day than other racial groups. Yet they experience higher rates of smoking-related mortality.
 

The reasons behind the attempts

Multiple factors play into Black smokers’ lower rates of successful quitting attempts than Asian, Hispanic, White, and Native American individuals.

One reason: An estimated 85% of Black smokers smoke highly addictive menthol cigarettes. According to Dr. Choi and other experts, the tobacco industry engages in targeted marketing of menthols by sponsoring community events in predominantly Black neighborhoods and colleges with historically Black populations and by using Black culture in advertising.

“The built environment really drives a change in behavior, and we have seen that chronically in the African American population being overly targeted and now being overly addicted to nicotine,” said Daniel Kortsch, MD, a family medicine physician and chair of the Tobacco Cessation Workgroup at Denver Health.

Menthol cigarettes are more addictive than traditional cigarettes, in part because they provide a less harsh feeling in the respiratory system, owing to anti-tussive, anti-irritant, and cooling properties that act as a cough suppressant and mask irritation and pain.

“You do not feel like you’re smoking that much or that it’s dangerous, and that’s exactly the reason why it’s harder to quit,” said Julia Adamian, MD, section chief of general internal medicine and clinical innovation at NYU Langone Tisch Hospital.

In addition, menthol cigarettes interact with the body in complex ways that make quitting harder, according to a study published in Nicotine & Tobacco Research. Menthol increases the amount of nicotine that the body absorbs and thus increases the risk of dependence on the drug.

According to Dr. Choi, rates of cigar and cigarillo use are higher among Black Americans, compared with other races, and these products are often left out of cessation programs. Smokers, regardless of race, may have a misguided belief that cigars and cigarillos are less harmful than cigarettes.

Research published in 2021 found that Black cigar smokers who were interested in cessation had not been asked by their health care provider if they smoked cigars, and those who were asked reported a lack of support for cessation.

Primary care providers should work to remove any misconceptions a patient has regarding the safety of cigarillos and cigars, Dr. Choi said.

These smokers are also at a disadvantage regarding cessation success because of the neighborhoods they may live in, according to Dr. Choi. Black Americans are more likely to earn less and to live in neighborhoods with lower housing values than other racial groups. Areas with more low-income households tend to have a higher density of tobacco outlets.

“If you’re trying to quit smoking, but you walk by three, four, or five gas stations, convenience stores, and other tobacco outlets with signs that advertise sales, it’s not going to make quitting easy,” Dr. Choi said.
 

Tailoring treatment to Black smokers

Considering the unique challenges Black patients may face in quitting, clinicians should provide more follow-up and consistent support, according to Dr. Adamian. The higher risk of tobacco-related death among Black smokers means clinicians need to be more aggressive in recommending every treatment possible if one treatment fails.

Pharmacotherapy, nicotine replacement therapy, and counseling are evidence-based options to help patients stop smoking.

Dr. Kortsch considers pharmacotherapy to be the most effective and evidence-based treatment for nicotine addiction. However, Black Americans are less likely than White smokers to try smoking cessation medications, and they express more suspicion about efficacy and potential addiction to the tools.

“African American populations simply do not use pharmacotherapy to the extent that other populations do to help them quit smoking; this is a problem,” Dr. Kortsch said.

Dr. Kortsch recommends the use of varenicline for all patients with nicotine addiction. He recommends varenicline in combination with tobacco replacement products such as lozenges, patches, gums, or inhalers if the patient is a heavy smoker as opposed to someone who has a few cigarettes on the weekends.

If a patient has anxiety or depression, Dr. Adamian advises initiating a pharmacologic treatment such as bupropion or varenicline more quickly, because mood disorders can hinder cessation.

Cessation counseling is another option, but clinicians may need to more thoroughly explain what it entails. According to Dr. Choi, Black patients may be more reluctant to try cessation counseling because of the negative stigma associated with the term “counseling.” But this treatment is not therapy – it involves identifying and coming up with strategies to manage smoking triggers and providing encouragement. Clinicians can eliminate any confusion patients may have between psychological therapy and cessation counseling.

“ ‘Counseling’ tends to have a somewhat negative connotation among racial minority populations, like you go to counseling because you’re crazy,” Dr. Choi said. “That needs to change.”

Clinicians also must clarify how each cessation tool works. For example, some patients may not realize that the nicotine patch isn’t an instant fix for a craving and that hours may pass before the user feels its effects, according to Dr. Choi.
 

Move past the ‘advise’ stage

While recommending to patients various forms of cessation, clinicians should be mindful of the U.S. Preventive Services Task Force’s guidelines for providers who treat patients who smoke. Those guidelines include a five-step process: Ask, Advise, Assess, Assist, and Arrange.

Dr. Choi said most providers stop at the “Advise” stage. In steps one and two, providers ask patients whether they smoke, then advise them to quit. Stage three involves asking whether or not a patient is ready to quit and where they are in their journey.

Clinicians shouldn’t give up when patients say they do not currently plan to quit. Instead, they can use the conversation to create an ongoing dialogue about the patient’s readiness to quit in future visits. Follow-up phone calls or text messages should be made 2-4 weeks after a patient makes an attempt to quit and at the same interval thereafter, Dr. Adamian advised.

“It takes a concerted effort on behalf of all people to be successful, and it is really uncommon for someone to be successful with only one attempt,” Dr. Kortsch said.

In a recent study published in the Journal of the American Medical Association, researchers identified three key factors that influence a Black smoker’s ability to stop smoking in early attempts. These factors have been shown to increase the chances of long-term cessation: fewer cigarettes per day, nonuse of other tobacco products, and lower levels of cotinine (a nicotine metabolite) at baseline.

“Using these predictors of early treatment response could allow providers to anticipate which smokers may benefit from a minimal, low-cost intervention and who may benefit from more intensive treatment,” said Eleanor Leavens, PhD, assistant professor in the department of population health at the University of Kansas School of Medicine, Kansas City, who led the study.

Dr. Leavens’ research also confirmed that early abstinence predicts long-term cessation success. Smokers who were able to forgo cigarettes within 2 weeks of their quit date were almost four times more likely to remain abstinent over the long term.

A quick phone call or message from the clinician or a staff member can help patients achieve early progress, enable changes in approach to quitting, and build a relationship with the patient, Dr. Adamian said.

“Have more empathy for what Black patients are going through,” Dr. Choi said. “Continue to cheer them on and to be a supporter of their smoking cessation journey.”

A version of this article first appeared on Medscape.com.

Black Americans attempt to quit smoking more often than their White counterparts but are less likely to succeed, and they pay the health consequences.

This knowledge has driven Kevin Choi, MD, acting scientific director of the National Institute on Minority Health and Health Disparities in Bethesda, Md., to dedicate his career to studying the patterns and disparities of smoking among these patients.

Dr. Choi wants primary care clinicians to know not just that they have the potential to educate patients on the harms of smoking – most patients already know smoking is unhealthy – but that aiding them will likely necessitate more assertive follow-up.

To do so, “we need to understand the bigger backdrop of racial and sociological stress experienced by the Black population, which stems from both interpersonal and structural racism,” Dr. Choi said.

Not only are Black smokers more likely to try to quit, but they also tend to smoke fewer cigarettes per day than other racial groups. Yet they experience higher rates of smoking-related mortality.
 

The reasons behind the attempts

Multiple factors play into Black smokers’ lower rates of successful quitting attempts than Asian, Hispanic, White, and Native American individuals.

One reason: An estimated 85% of Black smokers smoke highly addictive menthol cigarettes. According to Dr. Choi and other experts, the tobacco industry engages in targeted marketing of menthols by sponsoring community events in predominantly Black neighborhoods and colleges with historically Black populations and by using Black culture in advertising.

“The built environment really drives a change in behavior, and we have seen that chronically in the African American population being overly targeted and now being overly addicted to nicotine,” said Daniel Kortsch, MD, a family medicine physician and chair of the Tobacco Cessation Workgroup at Denver Health.

Menthol cigarettes are more addictive than traditional cigarettes, in part because they provide a less harsh feeling in the respiratory system, owing to anti-tussive, anti-irritant, and cooling properties that act as a cough suppressant and mask irritation and pain.

“You do not feel like you’re smoking that much or that it’s dangerous, and that’s exactly the reason why it’s harder to quit,” said Julia Adamian, MD, section chief of general internal medicine and clinical innovation at NYU Langone Tisch Hospital.

In addition, menthol cigarettes interact with the body in complex ways that make quitting harder, according to a study published in Nicotine & Tobacco Research. Menthol increases the amount of nicotine that the body absorbs and thus increases the risk of dependence on the drug.

According to Dr. Choi, rates of cigar and cigarillo use are higher among Black Americans, compared with other races, and these products are often left out of cessation programs. Smokers, regardless of race, may have a misguided belief that cigars and cigarillos are less harmful than cigarettes.

Research published in 2021 found that Black cigar smokers who were interested in cessation had not been asked by their health care provider if they smoked cigars, and those who were asked reported a lack of support for cessation.

Primary care providers should work to remove any misconceptions a patient has regarding the safety of cigarillos and cigars, Dr. Choi said.

These smokers are also at a disadvantage regarding cessation success because of the neighborhoods they may live in, according to Dr. Choi. Black Americans are more likely to earn less and to live in neighborhoods with lower housing values than other racial groups. Areas with more low-income households tend to have a higher density of tobacco outlets.

“If you’re trying to quit smoking, but you walk by three, four, or five gas stations, convenience stores, and other tobacco outlets with signs that advertise sales, it’s not going to make quitting easy,” Dr. Choi said.
 

Tailoring treatment to Black smokers

Considering the unique challenges Black patients may face in quitting, clinicians should provide more follow-up and consistent support, according to Dr. Adamian. The higher risk of tobacco-related death among Black smokers means clinicians need to be more aggressive in recommending every treatment possible if one treatment fails.

Pharmacotherapy, nicotine replacement therapy, and counseling are evidence-based options to help patients stop smoking.

Dr. Kortsch considers pharmacotherapy to be the most effective and evidence-based treatment for nicotine addiction. However, Black Americans are less likely than White smokers to try smoking cessation medications, and they express more suspicion about efficacy and potential addiction to the tools.

“African American populations simply do not use pharmacotherapy to the extent that other populations do to help them quit smoking; this is a problem,” Dr. Kortsch said.

Dr. Kortsch recommends the use of varenicline for all patients with nicotine addiction. He recommends varenicline in combination with tobacco replacement products such as lozenges, patches, gums, or inhalers if the patient is a heavy smoker as opposed to someone who has a few cigarettes on the weekends.

If a patient has anxiety or depression, Dr. Adamian advises initiating a pharmacologic treatment such as bupropion or varenicline more quickly, because mood disorders can hinder cessation.

Cessation counseling is another option, but clinicians may need to more thoroughly explain what it entails. According to Dr. Choi, Black patients may be more reluctant to try cessation counseling because of the negative stigma associated with the term “counseling.” But this treatment is not therapy – it involves identifying and coming up with strategies to manage smoking triggers and providing encouragement. Clinicians can eliminate any confusion patients may have between psychological therapy and cessation counseling.

“ ‘Counseling’ tends to have a somewhat negative connotation among racial minority populations, like you go to counseling because you’re crazy,” Dr. Choi said. “That needs to change.”

Clinicians also must clarify how each cessation tool works. For example, some patients may not realize that the nicotine patch isn’t an instant fix for a craving and that hours may pass before the user feels its effects, according to Dr. Choi.
 

Move past the ‘advise’ stage

While recommending to patients various forms of cessation, clinicians should be mindful of the U.S. Preventive Services Task Force’s guidelines for providers who treat patients who smoke. Those guidelines include a five-step process: Ask, Advise, Assess, Assist, and Arrange.

Dr. Choi said most providers stop at the “Advise” stage. In steps one and two, providers ask patients whether they smoke, then advise them to quit. Stage three involves asking whether or not a patient is ready to quit and where they are in their journey.

Clinicians shouldn’t give up when patients say they do not currently plan to quit. Instead, they can use the conversation to create an ongoing dialogue about the patient’s readiness to quit in future visits. Follow-up phone calls or text messages should be made 2-4 weeks after a patient makes an attempt to quit and at the same interval thereafter, Dr. Adamian advised.

“It takes a concerted effort on behalf of all people to be successful, and it is really uncommon for someone to be successful with only one attempt,” Dr. Kortsch said.

In a recent study published in the Journal of the American Medical Association, researchers identified three key factors that influence a Black smoker’s ability to stop smoking in early attempts. These factors have been shown to increase the chances of long-term cessation: fewer cigarettes per day, nonuse of other tobacco products, and lower levels of cotinine (a nicotine metabolite) at baseline.

“Using these predictors of early treatment response could allow providers to anticipate which smokers may benefit from a minimal, low-cost intervention and who may benefit from more intensive treatment,” said Eleanor Leavens, PhD, assistant professor in the department of population health at the University of Kansas School of Medicine, Kansas City, who led the study.

Dr. Leavens’ research also confirmed that early abstinence predicts long-term cessation success. Smokers who were able to forgo cigarettes within 2 weeks of their quit date were almost four times more likely to remain abstinent over the long term.

A quick phone call or message from the clinician or a staff member can help patients achieve early progress, enable changes in approach to quitting, and build a relationship with the patient, Dr. Adamian said.

“Have more empathy for what Black patients are going through,” Dr. Choi said. “Continue to cheer them on and to be a supporter of their smoking cessation journey.”

A version of this article first appeared on Medscape.com.

Black Americans attempt to quit smoking more often than their White counterparts but are less likely to succeed, and they pay the health consequences.

This knowledge has driven Kevin Choi, MD, acting scientific director of the National Institute on Minority Health and Health Disparities in Bethesda, Md., to dedicate his career to studying the patterns and disparities of smoking among these patients.

Dr. Choi wants primary care clinicians to know not just that they have the potential to educate patients on the harms of smoking – most patients already know smoking is unhealthy – but that aiding them will likely necessitate more assertive follow-up.

To do so, “we need to understand the bigger backdrop of racial and sociological stress experienced by the Black population, which stems from both interpersonal and structural racism,” Dr. Choi said.

Not only are Black smokers more likely to try to quit, but they also tend to smoke fewer cigarettes per day than other racial groups. Yet they experience higher rates of smoking-related mortality.
 

The reasons behind the attempts

Multiple factors play into Black smokers’ lower rates of successful quitting attempts than Asian, Hispanic, White, and Native American individuals.

One reason: An estimated 85% of Black smokers smoke highly addictive menthol cigarettes. According to Dr. Choi and other experts, the tobacco industry engages in targeted marketing of menthols by sponsoring community events in predominantly Black neighborhoods and colleges with historically Black populations and by using Black culture in advertising.

“The built environment really drives a change in behavior, and we have seen that chronically in the African American population being overly targeted and now being overly addicted to nicotine,” said Daniel Kortsch, MD, a family medicine physician and chair of the Tobacco Cessation Workgroup at Denver Health.

Menthol cigarettes are more addictive than traditional cigarettes, in part because they provide a less harsh feeling in the respiratory system, owing to anti-tussive, anti-irritant, and cooling properties that act as a cough suppressant and mask irritation and pain.

“You do not feel like you’re smoking that much or that it’s dangerous, and that’s exactly the reason why it’s harder to quit,” said Julia Adamian, MD, section chief of general internal medicine and clinical innovation at NYU Langone Tisch Hospital.

In addition, menthol cigarettes interact with the body in complex ways that make quitting harder, according to a study published in Nicotine & Tobacco Research. Menthol increases the amount of nicotine that the body absorbs and thus increases the risk of dependence on the drug.

According to Dr. Choi, rates of cigar and cigarillo use are higher among Black Americans, compared with other races, and these products are often left out of cessation programs. Smokers, regardless of race, may have a misguided belief that cigars and cigarillos are less harmful than cigarettes.

Research published in 2021 found that Black cigar smokers who were interested in cessation had not been asked by their health care provider if they smoked cigars, and those who were asked reported a lack of support for cessation.

Primary care providers should work to remove any misconceptions a patient has regarding the safety of cigarillos and cigars, Dr. Choi said.

These smokers are also at a disadvantage regarding cessation success because of the neighborhoods they may live in, according to Dr. Choi. Black Americans are more likely to earn less and to live in neighborhoods with lower housing values than other racial groups. Areas with more low-income households tend to have a higher density of tobacco outlets.

“If you’re trying to quit smoking, but you walk by three, four, or five gas stations, convenience stores, and other tobacco outlets with signs that advertise sales, it’s not going to make quitting easy,” Dr. Choi said.
 

Tailoring treatment to Black smokers

Considering the unique challenges Black patients may face in quitting, clinicians should provide more follow-up and consistent support, according to Dr. Adamian. The higher risk of tobacco-related death among Black smokers means clinicians need to be more aggressive in recommending every treatment possible if one treatment fails.

Pharmacotherapy, nicotine replacement therapy, and counseling are evidence-based options to help patients stop smoking.

Dr. Kortsch considers pharmacotherapy to be the most effective and evidence-based treatment for nicotine addiction. However, Black Americans are less likely than White smokers to try smoking cessation medications, and they express more suspicion about efficacy and potential addiction to the tools.

“African American populations simply do not use pharmacotherapy to the extent that other populations do to help them quit smoking; this is a problem,” Dr. Kortsch said.

Dr. Kortsch recommends the use of varenicline for all patients with nicotine addiction. He recommends varenicline in combination with tobacco replacement products such as lozenges, patches, gums, or inhalers if the patient is a heavy smoker as opposed to someone who has a few cigarettes on the weekends.

If a patient has anxiety or depression, Dr. Adamian advises initiating a pharmacologic treatment such as bupropion or varenicline more quickly, because mood disorders can hinder cessation.

Cessation counseling is another option, but clinicians may need to more thoroughly explain what it entails. According to Dr. Choi, Black patients may be more reluctant to try cessation counseling because of the negative stigma associated with the term “counseling.” But this treatment is not therapy – it involves identifying and coming up with strategies to manage smoking triggers and providing encouragement. Clinicians can eliminate any confusion patients may have between psychological therapy and cessation counseling.

“ ‘Counseling’ tends to have a somewhat negative connotation among racial minority populations, like you go to counseling because you’re crazy,” Dr. Choi said. “That needs to change.”

Clinicians also must clarify how each cessation tool works. For example, some patients may not realize that the nicotine patch isn’t an instant fix for a craving and that hours may pass before the user feels its effects, according to Dr. Choi.
 

Move past the ‘advise’ stage

While recommending to patients various forms of cessation, clinicians should be mindful of the U.S. Preventive Services Task Force’s guidelines for providers who treat patients who smoke. Those guidelines include a five-step process: Ask, Advise, Assess, Assist, and Arrange.

Dr. Choi said most providers stop at the “Advise” stage. In steps one and two, providers ask patients whether they smoke, then advise them to quit. Stage three involves asking whether or not a patient is ready to quit and where they are in their journey.

Clinicians shouldn’t give up when patients say they do not currently plan to quit. Instead, they can use the conversation to create an ongoing dialogue about the patient’s readiness to quit in future visits. Follow-up phone calls or text messages should be made 2-4 weeks after a patient makes an attempt to quit and at the same interval thereafter, Dr. Adamian advised.

“It takes a concerted effort on behalf of all people to be successful, and it is really uncommon for someone to be successful with only one attempt,” Dr. Kortsch said.

In a recent study published in the Journal of the American Medical Association, researchers identified three key factors that influence a Black smoker’s ability to stop smoking in early attempts. These factors have been shown to increase the chances of long-term cessation: fewer cigarettes per day, nonuse of other tobacco products, and lower levels of cotinine (a nicotine metabolite) at baseline.

“Using these predictors of early treatment response could allow providers to anticipate which smokers may benefit from a minimal, low-cost intervention and who may benefit from more intensive treatment,” said Eleanor Leavens, PhD, assistant professor in the department of population health at the University of Kansas School of Medicine, Kansas City, who led the study.

Dr. Leavens’ research also confirmed that early abstinence predicts long-term cessation success. Smokers who were able to forgo cigarettes within 2 weeks of their quit date were almost four times more likely to remain abstinent over the long term.

A quick phone call or message from the clinician or a staff member can help patients achieve early progress, enable changes in approach to quitting, and build a relationship with the patient, Dr. Adamian said.

“Have more empathy for what Black patients are going through,” Dr. Choi said. “Continue to cheer them on and to be a supporter of their smoking cessation journey.”

A version of this article first appeared on Medscape.com.

Alectinib, a potent anaplastic lymphoma kinase (ALK) inhibitor, significantly improved disease-free survival (DFS) at 2 years, compared with chemotherapy, in patients with completely resected ALK+ non–small cell lung cancer (NSCLC), according to interim findings from the open-label phase 3 ALINA trial.

The results suggest that alectinib, which is currently the first-line treatment choice in more advanced NSCLC, also provides an effective new treatment strategy for patients with resected ALK+ NSCLC, said Ben Solomon, MBBS, PhD, who presented late-breaking data from the trial at the annual meeting of the European Society for Medical Oncology.

ALINA is the first phase 3 trial of an ALK inhibitor to show a DFS benefit in completely resected stage IB-IIIA disease, said Dr. Solomon, professor and medical oncologist at Peter MacCallum Cancer Centre, Melbourne.

The current treatment recommendation for after surgery in this patient population is platinum-based chemotherapy, which is associated with modest improvements in overall survival. But multiple trials looking at alectinib in stage I-III NSCLC are underway given the unmet need for treatment in the 4%-5% of NSCLC patients with ALK rearrangements, Dr. Solomon explained.

The ALINA trial enrolled adults with good performance status and completely resected stage IB-IIIA ALK+ NSCLC. Patients were randomized 1:1 to 600 mg of oral alectinib twice daily for up to 24 months or until disease recurrence, or up to four 21-day cycles of intravenous platinum-based chemotherapy.

At median follow-up of 27.8 months, Dr. Solomon and colleagues observed an overall DFS benefit in 130 patients with stage II-IIIA disease randomized to receive alectinib, compared with the 127 patients who received chemotherapy (median DFS not reached vs. 44.4 months; hazard ratio, 0.24). The benefit was observed in the overall intention-to-treat (ITT) population of patients with stage IB-IIIA disease (median DFS not reached vs. 41.3 months; HR, 0.24).

Two-year DFS was also improved with alectinib vs. chemotherapy for stage IB (HR, 0.21), stage II (HR, 0.24), and stage IIIA disease (HR, 0.25).

The investigators observed a clinically meaningful central nervous system DFS benefit in the ITT population as well (HR, 0.22). This finding is important, given that patients with ALK+ disease have a high risk of brain metastases, which occurs in 50%-60% of patients over the course of disease, Dr. Solomon noted.

Over the treatment duration in each arm, 23.4% of patients in the alectinib arm and 25.8% in the chemotherapy arm experienced grade 3 or 4 adverse events; 5 patients in the alectinib arm and 13 in the chemotherapy arm had adverse events that led to treatment discontinuation.

“Adjuvant alectinib was tolerable and in line with the known safety profile of alectinib,” Dr. Solomon concluded, but noted that the overall survival data were not yet mature.

Invited discussant Marina Garassino, MBBS, however, cautioned against rushing to judgment, calling the DFS findings “interesting, but early.”

“Are 2 years of alectinib enough to impact overall survival? We don’t know yet,” said Dr. Garassino, professor of medicine and director of the thoracic oncology program at the University of Chicago.

Chemotherapy, conversely, has been shown to improve overall survival, she noted.

Toxicity of alectinib in the adjuvant setting may be a concern as well, she said, explaining that patients have reported numerous side effects that can affect quality of life, such as sun sensitivity, difficulty focusing, neuropathy, lower back muscle soreness, and constipation.

“So, I think we should still wait for more results from this trial,” she said.

In the meantime, she said she will ask patients “if they want this kind of toxicity in the absence of a clear overall survival benefit.”

The ALINA trial is funded by F. Hoffmann-La Roche. Dr. Solomon and Dr. Garassino each reported numerous relationships with pharmaceutical companies and other entities.

A version of this article first appeared on Medscape.com. 

Alectinib, a potent anaplastic lymphoma kinase (ALK) inhibitor, significantly improved disease-free survival (DFS) at 2 years, compared with chemotherapy, in patients with completely resected ALK+ non–small cell lung cancer (NSCLC), according to interim findings from the open-label phase 3 ALINA trial.

The results suggest that alectinib, which is currently the first-line treatment choice in more advanced NSCLC, also provides an effective new treatment strategy for patients with resected ALK+ NSCLC, said Ben Solomon, MBBS, PhD, who presented late-breaking data from the trial at the annual meeting of the European Society for Medical Oncology.

ALINA is the first phase 3 trial of an ALK inhibitor to show a DFS benefit in completely resected stage IB-IIIA disease, said Dr. Solomon, professor and medical oncologist at Peter MacCallum Cancer Centre, Melbourne.

The current treatment recommendation for after surgery in this patient population is platinum-based chemotherapy, which is associated with modest improvements in overall survival. But multiple trials looking at alectinib in stage I-III NSCLC are underway given the unmet need for treatment in the 4%-5% of NSCLC patients with ALK rearrangements, Dr. Solomon explained.

The ALINA trial enrolled adults with good performance status and completely resected stage IB-IIIA ALK+ NSCLC. Patients were randomized 1:1 to 600 mg of oral alectinib twice daily for up to 24 months or until disease recurrence, or up to four 21-day cycles of intravenous platinum-based chemotherapy.

At median follow-up of 27.8 months, Dr. Solomon and colleagues observed an overall DFS benefit in 130 patients with stage II-IIIA disease randomized to receive alectinib, compared with the 127 patients who received chemotherapy (median DFS not reached vs. 44.4 months; hazard ratio, 0.24). The benefit was observed in the overall intention-to-treat (ITT) population of patients with stage IB-IIIA disease (median DFS not reached vs. 41.3 months; HR, 0.24).

Two-year DFS was also improved with alectinib vs. chemotherapy for stage IB (HR, 0.21), stage II (HR, 0.24), and stage IIIA disease (HR, 0.25).

The investigators observed a clinically meaningful central nervous system DFS benefit in the ITT population as well (HR, 0.22). This finding is important, given that patients with ALK+ disease have a high risk of brain metastases, which occurs in 50%-60% of patients over the course of disease, Dr. Solomon noted.

Over the treatment duration in each arm, 23.4% of patients in the alectinib arm and 25.8% in the chemotherapy arm experienced grade 3 or 4 adverse events; 5 patients in the alectinib arm and 13 in the chemotherapy arm had adverse events that led to treatment discontinuation.

“Adjuvant alectinib was tolerable and in line with the known safety profile of alectinib,” Dr. Solomon concluded, but noted that the overall survival data were not yet mature.

Invited discussant Marina Garassino, MBBS, however, cautioned against rushing to judgment, calling the DFS findings “interesting, but early.”

“Are 2 years of alectinib enough to impact overall survival? We don’t know yet,” said Dr. Garassino, professor of medicine and director of the thoracic oncology program at the University of Chicago.

Chemotherapy, conversely, has been shown to improve overall survival, she noted.

Toxicity of alectinib in the adjuvant setting may be a concern as well, she said, explaining that patients have reported numerous side effects that can affect quality of life, such as sun sensitivity, difficulty focusing, neuropathy, lower back muscle soreness, and constipation.

“So, I think we should still wait for more results from this trial,” she said.

In the meantime, she said she will ask patients “if they want this kind of toxicity in the absence of a clear overall survival benefit.”

The ALINA trial is funded by F. Hoffmann-La Roche. Dr. Solomon and Dr. Garassino each reported numerous relationships with pharmaceutical companies and other entities.

A version of this article first appeared on Medscape.com. 

Alectinib, a potent anaplastic lymphoma kinase (ALK) inhibitor, significantly improved disease-free survival (DFS) at 2 years, compared with chemotherapy, in patients with completely resected ALK+ non–small cell lung cancer (NSCLC), according to interim findings from the open-label phase 3 ALINA trial.

The results suggest that alectinib, which is currently the first-line treatment choice in more advanced NSCLC, also provides an effective new treatment strategy for patients with resected ALK+ NSCLC, said Ben Solomon, MBBS, PhD, who presented late-breaking data from the trial at the annual meeting of the European Society for Medical Oncology.

ALINA is the first phase 3 trial of an ALK inhibitor to show a DFS benefit in completely resected stage IB-IIIA disease, said Dr. Solomon, professor and medical oncologist at Peter MacCallum Cancer Centre, Melbourne.

The current treatment recommendation for after surgery in this patient population is platinum-based chemotherapy, which is associated with modest improvements in overall survival. But multiple trials looking at alectinib in stage I-III NSCLC are underway given the unmet need for treatment in the 4%-5% of NSCLC patients with ALK rearrangements, Dr. Solomon explained.

The ALINA trial enrolled adults with good performance status and completely resected stage IB-IIIA ALK+ NSCLC. Patients were randomized 1:1 to 600 mg of oral alectinib twice daily for up to 24 months or until disease recurrence, or up to four 21-day cycles of intravenous platinum-based chemotherapy.

At median follow-up of 27.8 months, Dr. Solomon and colleagues observed an overall DFS benefit in 130 patients with stage II-IIIA disease randomized to receive alectinib, compared with the 127 patients who received chemotherapy (median DFS not reached vs. 44.4 months; hazard ratio, 0.24). The benefit was observed in the overall intention-to-treat (ITT) population of patients with stage IB-IIIA disease (median DFS not reached vs. 41.3 months; HR, 0.24).

Two-year DFS was also improved with alectinib vs. chemotherapy for stage IB (HR, 0.21), stage II (HR, 0.24), and stage IIIA disease (HR, 0.25).

The investigators observed a clinically meaningful central nervous system DFS benefit in the ITT population as well (HR, 0.22). This finding is important, given that patients with ALK+ disease have a high risk of brain metastases, which occurs in 50%-60% of patients over the course of disease, Dr. Solomon noted.

Over the treatment duration in each arm, 23.4% of patients in the alectinib arm and 25.8% in the chemotherapy arm experienced grade 3 or 4 adverse events; 5 patients in the alectinib arm and 13 in the chemotherapy arm had adverse events that led to treatment discontinuation.

“Adjuvant alectinib was tolerable and in line with the known safety profile of alectinib,” Dr. Solomon concluded, but noted that the overall survival data were not yet mature.

Invited discussant Marina Garassino, MBBS, however, cautioned against rushing to judgment, calling the DFS findings “interesting, but early.”

“Are 2 years of alectinib enough to impact overall survival? We don’t know yet,” said Dr. Garassino, professor of medicine and director of the thoracic oncology program at the University of Chicago.

Chemotherapy, conversely, has been shown to improve overall survival, she noted.

Toxicity of alectinib in the adjuvant setting may be a concern as well, she said, explaining that patients have reported numerous side effects that can affect quality of life, such as sun sensitivity, difficulty focusing, neuropathy, lower back muscle soreness, and constipation.

“So, I think we should still wait for more results from this trial,” she said.

In the meantime, she said she will ask patients “if they want this kind of toxicity in the absence of a clear overall survival benefit.”

The ALINA trial is funded by F. Hoffmann-La Roche. Dr. Solomon and Dr. Garassino each reported numerous relationships with pharmaceutical companies and other entities.

A version of this article first appeared on Medscape.com. 

Neoadjuvant nivolumab (Opdivo) plus chemotherapy followed by adjuvant nivolumab led to a statistically significant and clinically meaningful improvement in event-free survival (EFS) in patients with resectable non–small cell lung cancer (NSCLC), according to interim findings from the phase 3 CheckMate 77T trial.

In the interim analysis, median EFS was not reached in 229 patients randomly assigned to the adjuvant nivolumab treatment group vs. 18.4 months in 232 patients randomly assigned to a placebo group over a minimum follow-up of 15.7 months (hazard ratio, 0.58), first author Tina Cascone, MD, reported at the annual meeting of the European Society for Medical Oncology.

“CheckMate 77T is the first phase 3 perioperative study to build on the standard of care neoadjuvant nivolumab plus chemotherapy and supports perioperative nivolumab as a potential new treatment option for patients with resectable non–small cell lung cancer,” said Dr. Cascone, associate professor in the division of cancer medicine at University of Texas MD Anderson Cancer Center, Houston.

Invited discussant Marina Garassino, MBBS, professor of medicine and director of the thoracic oncology program at the University of Chicago, noted that the “practice-changing” CheckMate 77T findings – including the “highly statistically significant impressive hazard ratio of 0.58” – add to the increasing evidence supporting perioperative immunochemotherapy in the resectable NSCLC space.

This trial is the fourth to show an EFS benefit in this setting with a perioperative approach. Most recently, Merck’s pembrolizumab (Keytruda) demonstrated improvements in both EFS and overall survival when used in the perioperative setting for patients with resectable NSCLC, according to data from the pivotal KEYNOTE-671 trial. Those findings, also presented at the ESMO congress, led to the approval this past week of pembrolizumab in that population.

The CheckMate 77T included 461 adults with untreated resectable stage IIA-IIIB NSCLC, 77% of whom underwent definitive surgery. The median age of participants was 66 years. Patients were randomly assigned to active treatment with nivolumab plus platinum-doublet chemotherapy followed by surgery and adjuvant nivolumab or placebo. The neoadjuvant nivolumab dose was 360 mg every 3 weeks for four cycles, and the adjuvant dose was 480 mg every 4 weeks for 1 year.

Overall, adding adjuvant nivolumab led to a significant improvement in EFS over a follow-up spanning 15.7-44.2 months (not reached vs. 18.4 months; HR, 0.58; P = .00025).

The EFS benefits were observed across most key subgroups but was lower in patients with stage II vs. stage III disease (HR, 0.81 vs. 0.51), and in those with programmed death-ligand 1 (PD-L1) expression of less than 1% vs. 1% or greater (HR, 0.73 vs. 0.52).

Neoadjuvant/adjuvant nivolumab also led to a significant improvement in pathological complete response (25.3% vs. 4.7%; odds ratio, 6.64) and major pathological response (35.4% vs. 12.1%; OR, 4.01) – the trial’s secondary endpoints.

In an exploratory analysis, perioperative nivolumab showed a trend toward improved EFS in patients without a pathological complete response, Dr. Cascone added.

No new safety signals were observed. Grade 3-4 treatment-related adverse events occurred in 32% of patients in the treatment arm and 25% in the placebo arm. Surgery-related adverse events occurred in 12% in each arm.

Despite the promising findings, some questions remain, said Dr. Garassino.

First, should PD-L1–negative patients and those with stage II NSCLC receive perioperative treatment? Pooled data from recent perioperative trials indicated EFS benefits in the perioperative setting for both PD-L1-negative disease (HR, 0.72) and stage II disease (HR, 0.68), she said.

So, “the answer is yes, we should treat” these patients, she said.

But a big question is whether patients who don’t achieve a pathological complete response need adjuvant therapy. “We really don’t know,” she continued. “What we know is that those patients who achieve pathological complete response do very, very well, and I think for those patients who don’t achieve pathological complete response, we have to work with new biomarkers, [circulating tumor] DNA, new drugs, and we have to run proper trials to increase the power of these patients, that unfortunately is still very low.”

CheckMate 77T is funded by Bristol-Myers Squibb. Dr. Cascone and Dr. Garassino each reported relationships (personal and institutional) with numerous pharmaceutical companies and other entities.

A version of this article first appeared on Medscape.com.

Neoadjuvant nivolumab (Opdivo) plus chemotherapy followed by adjuvant nivolumab led to a statistically significant and clinically meaningful improvement in event-free survival (EFS) in patients with resectable non–small cell lung cancer (NSCLC), according to interim findings from the phase 3 CheckMate 77T trial.

In the interim analysis, median EFS was not reached in 229 patients randomly assigned to the adjuvant nivolumab treatment group vs. 18.4 months in 232 patients randomly assigned to a placebo group over a minimum follow-up of 15.7 months (hazard ratio, 0.58), first author Tina Cascone, MD, reported at the annual meeting of the European Society for Medical Oncology.

“CheckMate 77T is the first phase 3 perioperative study to build on the standard of care neoadjuvant nivolumab plus chemotherapy and supports perioperative nivolumab as a potential new treatment option for patients with resectable non–small cell lung cancer,” said Dr. Cascone, associate professor in the division of cancer medicine at University of Texas MD Anderson Cancer Center, Houston.

Invited discussant Marina Garassino, MBBS, professor of medicine and director of the thoracic oncology program at the University of Chicago, noted that the “practice-changing” CheckMate 77T findings – including the “highly statistically significant impressive hazard ratio of 0.58” – add to the increasing evidence supporting perioperative immunochemotherapy in the resectable NSCLC space.

This trial is the fourth to show an EFS benefit in this setting with a perioperative approach. Most recently, Merck’s pembrolizumab (Keytruda) demonstrated improvements in both EFS and overall survival when used in the perioperative setting for patients with resectable NSCLC, according to data from the pivotal KEYNOTE-671 trial. Those findings, also presented at the ESMO congress, led to the approval this past week of pembrolizumab in that population.

The CheckMate 77T included 461 adults with untreated resectable stage IIA-IIIB NSCLC, 77% of whom underwent definitive surgery. The median age of participants was 66 years. Patients were randomly assigned to active treatment with nivolumab plus platinum-doublet chemotherapy followed by surgery and adjuvant nivolumab or placebo. The neoadjuvant nivolumab dose was 360 mg every 3 weeks for four cycles, and the adjuvant dose was 480 mg every 4 weeks for 1 year.

Overall, adding adjuvant nivolumab led to a significant improvement in EFS over a follow-up spanning 15.7-44.2 months (not reached vs. 18.4 months; HR, 0.58; P = .00025).

The EFS benefits were observed across most key subgroups but was lower in patients with stage II vs. stage III disease (HR, 0.81 vs. 0.51), and in those with programmed death-ligand 1 (PD-L1) expression of less than 1% vs. 1% or greater (HR, 0.73 vs. 0.52).

Neoadjuvant/adjuvant nivolumab also led to a significant improvement in pathological complete response (25.3% vs. 4.7%; odds ratio, 6.64) and major pathological response (35.4% vs. 12.1%; OR, 4.01) – the trial’s secondary endpoints.

In an exploratory analysis, perioperative nivolumab showed a trend toward improved EFS in patients without a pathological complete response, Dr. Cascone added.

No new safety signals were observed. Grade 3-4 treatment-related adverse events occurred in 32% of patients in the treatment arm and 25% in the placebo arm. Surgery-related adverse events occurred in 12% in each arm.

Despite the promising findings, some questions remain, said Dr. Garassino.

First, should PD-L1–negative patients and those with stage II NSCLC receive perioperative treatment? Pooled data from recent perioperative trials indicated EFS benefits in the perioperative setting for both PD-L1-negative disease (HR, 0.72) and stage II disease (HR, 0.68), she said.

So, “the answer is yes, we should treat” these patients, she said.

But a big question is whether patients who don’t achieve a pathological complete response need adjuvant therapy. “We really don’t know,” she continued. “What we know is that those patients who achieve pathological complete response do very, very well, and I think for those patients who don’t achieve pathological complete response, we have to work with new biomarkers, [circulating tumor] DNA, new drugs, and we have to run proper trials to increase the power of these patients, that unfortunately is still very low.”

CheckMate 77T is funded by Bristol-Myers Squibb. Dr. Cascone and Dr. Garassino each reported relationships (personal and institutional) with numerous pharmaceutical companies and other entities.

A version of this article first appeared on Medscape.com.

Neoadjuvant nivolumab (Opdivo) plus chemotherapy followed by adjuvant nivolumab led to a statistically significant and clinically meaningful improvement in event-free survival (EFS) in patients with resectable non–small cell lung cancer (NSCLC), according to interim findings from the phase 3 CheckMate 77T trial.

In the interim analysis, median EFS was not reached in 229 patients randomly assigned to the adjuvant nivolumab treatment group vs. 18.4 months in 232 patients randomly assigned to a placebo group over a minimum follow-up of 15.7 months (hazard ratio, 0.58), first author Tina Cascone, MD, reported at the annual meeting of the European Society for Medical Oncology.

“CheckMate 77T is the first phase 3 perioperative study to build on the standard of care neoadjuvant nivolumab plus chemotherapy and supports perioperative nivolumab as a potential new treatment option for patients with resectable non–small cell lung cancer,” said Dr. Cascone, associate professor in the division of cancer medicine at University of Texas MD Anderson Cancer Center, Houston.

Invited discussant Marina Garassino, MBBS, professor of medicine and director of the thoracic oncology program at the University of Chicago, noted that the “practice-changing” CheckMate 77T findings – including the “highly statistically significant impressive hazard ratio of 0.58” – add to the increasing evidence supporting perioperative immunochemotherapy in the resectable NSCLC space.

This trial is the fourth to show an EFS benefit in this setting with a perioperative approach. Most recently, Merck’s pembrolizumab (Keytruda) demonstrated improvements in both EFS and overall survival when used in the perioperative setting for patients with resectable NSCLC, according to data from the pivotal KEYNOTE-671 trial. Those findings, also presented at the ESMO congress, led to the approval this past week of pembrolizumab in that population.

The CheckMate 77T included 461 adults with untreated resectable stage IIA-IIIB NSCLC, 77% of whom underwent definitive surgery. The median age of participants was 66 years. Patients were randomly assigned to active treatment with nivolumab plus platinum-doublet chemotherapy followed by surgery and adjuvant nivolumab or placebo. The neoadjuvant nivolumab dose was 360 mg every 3 weeks for four cycles, and the adjuvant dose was 480 mg every 4 weeks for 1 year.

Overall, adding adjuvant nivolumab led to a significant improvement in EFS over a follow-up spanning 15.7-44.2 months (not reached vs. 18.4 months; HR, 0.58; P = .00025).

The EFS benefits were observed across most key subgroups but was lower in patients with stage II vs. stage III disease (HR, 0.81 vs. 0.51), and in those with programmed death-ligand 1 (PD-L1) expression of less than 1% vs. 1% or greater (HR, 0.73 vs. 0.52).

Neoadjuvant/adjuvant nivolumab also led to a significant improvement in pathological complete response (25.3% vs. 4.7%; odds ratio, 6.64) and major pathological response (35.4% vs. 12.1%; OR, 4.01) – the trial’s secondary endpoints.

In an exploratory analysis, perioperative nivolumab showed a trend toward improved EFS in patients without a pathological complete response, Dr. Cascone added.

No new safety signals were observed. Grade 3-4 treatment-related adverse events occurred in 32% of patients in the treatment arm and 25% in the placebo arm. Surgery-related adverse events occurred in 12% in each arm.

Despite the promising findings, some questions remain, said Dr. Garassino.

First, should PD-L1–negative patients and those with stage II NSCLC receive perioperative treatment? Pooled data from recent perioperative trials indicated EFS benefits in the perioperative setting for both PD-L1-negative disease (HR, 0.72) and stage II disease (HR, 0.68), she said.

So, “the answer is yes, we should treat” these patients, she said.

But a big question is whether patients who don’t achieve a pathological complete response need adjuvant therapy. “We really don’t know,” she continued. “What we know is that those patients who achieve pathological complete response do very, very well, and I think for those patients who don’t achieve pathological complete response, we have to work with new biomarkers, [circulating tumor] DNA, new drugs, and we have to run proper trials to increase the power of these patients, that unfortunately is still very low.”

CheckMate 77T is funded by Bristol-Myers Squibb. Dr. Cascone and Dr. Garassino each reported relationships (personal and institutional) with numerous pharmaceutical companies and other entities.

A version of this article first appeared on Medscape.com.

I’m speaking today about the ever-rising prominence of neoadjuvant therapy for patients with locally advanced lung cancers. There are more and more data emerging suggesting that the neoadjuvant strategy is a better one.

Many of you saw the press release from Merck announcing that their randomized trial comparing chemo with chemo plus pembrolizumab in the neoadjuvant setting led to improved event-free survival and also improved pathologic complete response rate.

This comes in addition to the data from the AstraZeneca trial with durvalumab saying they’ve already achieved their endpoint of higher pathologic complete response rate vs. chemotherapy alone and also the data with nivolumab from Bristol-Myers Squibb saying that nivolumab plus chemotherapy leads to a better event-free survival and a better pathologic complete response rate. That information has led to Food and Drug Administration approval for their regimen.

We’re running the table with these very positive data, and I think it’s just a sign that the approach is safe and effective.

A huge question has come up. I just came from a meeting of lung cancer experts asking what to do if you have a patient with a small tumor, for example, a 3-cm tumor. Do you recommend immediate surgery followed by adjuvant therapy, chemotherapy, and then a checkpoint inhibitor if appropriate? Or do you proceed with neoadjuvant therapy if appropriate? The truth is that it’s a very difficult decision.

We have overwhelming data that the neoadjuvant approach works for that patient. Please remember that this is a clinically staged patient. This is not the patient after their surgery, where I think we have a very clear path. We have adjuvant data and adjuvant trials for those patients.

For the patient who’s in your office with a small tumor or a small tumor and only hilar lymphadenopathy, the decision there isn’t data driven, but rather it is experience driven. The data that are out there right now suggest that neoadjuvant therapy is a better way to go. Why is that?

Well, I think that the first reason is that it is probably a better regimen. I think many of you saw the recent clinical trial by Patel and colleagues in the New England Journal of Medicine with melanoma. It was an interesting trial. They gave a checkpoint inhibitor for 18 doses after surgery for melanoma versus three doses of checkpoint inhibitor, surgery, and then 15 doses of the checkpoint inhibitor.

It was 18 doses versus 18 doses, with the only difference being the three doses before surgery. Lo and behold, the three doses before surgery led to a better event-free survival.

There are preclinical data in lung cancer demonstrating that the same thing is true. Tina Cascone published on that years ago. We could talk about why, but it appears that neoadjuvant is just better.

There are other advantages to it as well. I think a big one is that all the information shows that it’s better tolerated, so you’re more likely to give all the drug. You can see if the drug isn’t working, and you can stop the drug. Also, if the drug is causing a side effect, you can see whether it’s working or not and use that decision to stop. It’s different than when you’re giving a drug in the adjuvant setting where you don’t really know whether it is working or not.

I think that it’s time to change some of our standards. When patients appear with lung cancers other than tiny ones that might be detected through screening, you need to convene your multidisciplinary group. You need to weigh the pros and cons I think that it’s time to change some of our standards. When patients appear with lung cancers other than tiny ones that might be detected through screening, you need to convene your multidisciplinary group coming in. It’s already an FDA-approved regimen with nivolumab and chemotherapy, and I think we’re moving to making that our standard of care now.

The way to handle it today, though, is to convene your multidisciplinary panel about every patient other than those with the tiniest of lung cancers and put your heads together to see what the best treatment is for that patient.

Dr. Kris is professor of medicine, Weill Cornell Medicine, and the William and Joy Ruane Chair in Thoracic Oncology, Memorial Sloan Kettering Cancer Center, both in New York. He disclosed ties with Ariad Pharmaceuticals, AstraZeneca, Pfizer, PUMA, and Roche/Genentech.

A version of this article appeared on Medscape.com.

I’m speaking today about the ever-rising prominence of neoadjuvant therapy for patients with locally advanced lung cancers. There are more and more data emerging suggesting that the neoadjuvant strategy is a better one.

Many of you saw the press release from Merck announcing that their randomized trial comparing chemo with chemo plus pembrolizumab in the neoadjuvant setting led to improved event-free survival and also improved pathologic complete response rate.

This comes in addition to the data from the AstraZeneca trial with durvalumab saying they’ve already achieved their endpoint of higher pathologic complete response rate vs. chemotherapy alone and also the data with nivolumab from Bristol-Myers Squibb saying that nivolumab plus chemotherapy leads to a better event-free survival and a better pathologic complete response rate. That information has led to Food and Drug Administration approval for their regimen.

We’re running the table with these very positive data, and I think it’s just a sign that the approach is safe and effective.

A huge question has come up. I just came from a meeting of lung cancer experts asking what to do if you have a patient with a small tumor, for example, a 3-cm tumor. Do you recommend immediate surgery followed by adjuvant therapy, chemotherapy, and then a checkpoint inhibitor if appropriate? Or do you proceed with neoadjuvant therapy if appropriate? The truth is that it’s a very difficult decision.

We have overwhelming data that the neoadjuvant approach works for that patient. Please remember that this is a clinically staged patient. This is not the patient after their surgery, where I think we have a very clear path. We have adjuvant data and adjuvant trials for those patients.

For the patient who’s in your office with a small tumor or a small tumor and only hilar lymphadenopathy, the decision there isn’t data driven, but rather it is experience driven. The data that are out there right now suggest that neoadjuvant therapy is a better way to go. Why is that?

Well, I think that the first reason is that it is probably a better regimen. I think many of you saw the recent clinical trial by Patel and colleagues in the New England Journal of Medicine with melanoma. It was an interesting trial. They gave a checkpoint inhibitor for 18 doses after surgery for melanoma versus three doses of checkpoint inhibitor, surgery, and then 15 doses of the checkpoint inhibitor.

It was 18 doses versus 18 doses, with the only difference being the three doses before surgery. Lo and behold, the three doses before surgery led to a better event-free survival.

There are preclinical data in lung cancer demonstrating that the same thing is true. Tina Cascone published on that years ago. We could talk about why, but it appears that neoadjuvant is just better.

There are other advantages to it as well. I think a big one is that all the information shows that it’s better tolerated, so you’re more likely to give all the drug. You can see if the drug isn’t working, and you can stop the drug. Also, if the drug is causing a side effect, you can see whether it’s working or not and use that decision to stop. It’s different than when you’re giving a drug in the adjuvant setting where you don’t really know whether it is working or not.

I think that it’s time to change some of our standards. When patients appear with lung cancers other than tiny ones that might be detected through screening, you need to convene your multidisciplinary group. You need to weigh the pros and cons I think that it’s time to change some of our standards. When patients appear with lung cancers other than tiny ones that might be detected through screening, you need to convene your multidisciplinary group coming in. It’s already an FDA-approved regimen with nivolumab and chemotherapy, and I think we’re moving to making that our standard of care now.

The way to handle it today, though, is to convene your multidisciplinary panel about every patient other than those with the tiniest of lung cancers and put your heads together to see what the best treatment is for that patient.

Dr. Kris is professor of medicine, Weill Cornell Medicine, and the William and Joy Ruane Chair in Thoracic Oncology, Memorial Sloan Kettering Cancer Center, both in New York. He disclosed ties with Ariad Pharmaceuticals, AstraZeneca, Pfizer, PUMA, and Roche/Genentech.

A version of this article appeared on Medscape.com.

I’m speaking today about the ever-rising prominence of neoadjuvant therapy for patients with locally advanced lung cancers. There are more and more data emerging suggesting that the neoadjuvant strategy is a better one.

Many of you saw the press release from Merck announcing that their randomized trial comparing chemo with chemo plus pembrolizumab in the neoadjuvant setting led to improved event-free survival and also improved pathologic complete response rate.

This comes in addition to the data from the AstraZeneca trial with durvalumab saying they’ve already achieved their endpoint of higher pathologic complete response rate vs. chemotherapy alone and also the data with nivolumab from Bristol-Myers Squibb saying that nivolumab plus chemotherapy leads to a better event-free survival and a better pathologic complete response rate. That information has led to Food and Drug Administration approval for their regimen.

We’re running the table with these very positive data, and I think it’s just a sign that the approach is safe and effective.

A huge question has come up. I just came from a meeting of lung cancer experts asking what to do if you have a patient with a small tumor, for example, a 3-cm tumor. Do you recommend immediate surgery followed by adjuvant therapy, chemotherapy, and then a checkpoint inhibitor if appropriate? Or do you proceed with neoadjuvant therapy if appropriate? The truth is that it’s a very difficult decision.

We have overwhelming data that the neoadjuvant approach works for that patient. Please remember that this is a clinically staged patient. This is not the patient after their surgery, where I think we have a very clear path. We have adjuvant data and adjuvant trials for those patients.

For the patient who’s in your office with a small tumor or a small tumor and only hilar lymphadenopathy, the decision there isn’t data driven, but rather it is experience driven. The data that are out there right now suggest that neoadjuvant therapy is a better way to go. Why is that?

Well, I think that the first reason is that it is probably a better regimen. I think many of you saw the recent clinical trial by Patel and colleagues in the New England Journal of Medicine with melanoma. It was an interesting trial. They gave a checkpoint inhibitor for 18 doses after surgery for melanoma versus three doses of checkpoint inhibitor, surgery, and then 15 doses of the checkpoint inhibitor.

It was 18 doses versus 18 doses, with the only difference being the three doses before surgery. Lo and behold, the three doses before surgery led to a better event-free survival.

There are preclinical data in lung cancer demonstrating that the same thing is true. Tina Cascone published on that years ago. We could talk about why, but it appears that neoadjuvant is just better.

There are other advantages to it as well. I think a big one is that all the information shows that it’s better tolerated, so you’re more likely to give all the drug. You can see if the drug isn’t working, and you can stop the drug. Also, if the drug is causing a side effect, you can see whether it’s working or not and use that decision to stop. It’s different than when you’re giving a drug in the adjuvant setting where you don’t really know whether it is working or not.

I think that it’s time to change some of our standards. When patients appear with lung cancers other than tiny ones that might be detected through screening, you need to convene your multidisciplinary group. You need to weigh the pros and cons I think that it’s time to change some of our standards. When patients appear with lung cancers other than tiny ones that might be detected through screening, you need to convene your multidisciplinary group coming in. It’s already an FDA-approved regimen with nivolumab and chemotherapy, and I think we’re moving to making that our standard of care now.

The way to handle it today, though, is to convene your multidisciplinary panel about every patient other than those with the tiniest of lung cancers and put your heads together to see what the best treatment is for that patient.

Dr. Kris is professor of medicine, Weill Cornell Medicine, and the William and Joy Ruane Chair in Thoracic Oncology, Memorial Sloan Kettering Cancer Center, both in New York. He disclosed ties with Ariad Pharmaceuticals, AstraZeneca, Pfizer, PUMA, and Roche/Genentech.

A version of this article appeared on Medscape.com.

Screening for cancer is only half the battle: Patients often fail to complete recommended follow-up and additional testing after an abnormal result, leaving them at risk, according to authors of a new study published in the Journal of the American Medical Association.

Results from the clustered, randomized clinical trial indicate that systems-based interventions, such as automating reminders in electronic health records (EHRs), outreach in the form of phone calls or letters, and assistance with barriers to health care, such as housing insecurity, can increase the number of patients who complete appropriate diagnostic follow-up after an abnormal result.

Patients who received an EHR reminder, outreach call or letter, and additional calls to screen for and assist with nine barriers to health care – housing insecurity, food insecurity, paying for basic utilities, family caregiving, legal issues, transportation, financial compensation for treatment, education, and employment – completed follow-up within 120 days of study enrollment at a rate of 31.4%. The follow-up rate was 31% for those who received only an EHR reminder and outreach, 22.7% for those who received only an EHR reminder, and 22.9% for those who received usual care.

“The benefits of cancer screening won’t be fully realized without systems to ensure timely follow-up of abnormal results,” said Anna Tosteson, ScD, director of the Dartmouth Institute for Health Policy and Clinical Practice in Lebanon, N.H., a coauthor of the study.

Current payment incentives and quality-of-care indicators focus on getting people in for screening but should also address completion of screening – meaning timely and appropriate follow-up of results that could be indicative of cancer, Dr. Tosteson said.

“There’s a disconnect if you have screening rates that are high but once people have an abnormal result, which is potentially one step closer to a cancer diagnosis, there are no systems in place to help clinicians track them,” said study coauthor Jennifer Haas, MD, director of the Center for Primary Care Research at Massachusetts General Hospital in Boston.

In a 2016 study, researchers found that follow-up rates after abnormal cancer screenings varied widely. While 95.6% of patients with abnormal breast cancer screenings underwent timely follow-up testing, only 68.1% of patients with colorectal abnormalities and 44.8% of patients with cervical abnormalities did so.

Researchers for the new study used guideline recommendations and specialist input to create automated EHR algorithms that determined a follow-up period and diagnostic test.

They put the algorithm into practice with 11,980 patients who were part of 44 primary care practices within three health networks between August 2020 and December 2021. All patients had received abnormal test results for colorectal, breast, cervical, or lung cancer in varying risk categories.

All patients received usual care from their providers, which consisted of a “hodgepodge of whatever their clinic usually does,” Dr. Haas said. Without standards and systems in place for follow-up, the burden of testing and tracking patients with abnormal results typically falls on the primary care provider.

The researchers intervened only when patients were overdue for completion of follow-up. They then staggered the interventions sequentially.

All study participants received an automated, algorithm-triggered EHR reminder for follow-up in their patient portal along with routine health maintenance reminders. To view the reminder, patients had to log into their portal. Participants in the outreach and outreach and navigation groups also received a phone call, an EHR message, or a physical letter 2 weeks after receiving an EHR notification if they hadn’t completed follow-up. Research assistants performed the outreach after having been prompted by the algorithm.

After another 4 weeks, those in the EHR, outreach, and navigation group received a call from a patient navigator who helped them address nine barriers to health care, chiefly by providing them with referrals to free resources.

Among patients who received navigation, outcomes were not significantly better than among those who received EHR and outreach, indicating social determinants of health did not significantly affect the population studied or that the modest approach to navigation and the resources provided were insufficient, Dr. Haas said.

The complexity of an automated platform that encompasses many types of cancers, test results, and other data elements could prove difficult to apply in settings with less infrastructure, said Steven Atlas, MD, MPH, director of the Practice-Based Research and Quality Improvement Network in the division of general internal medicine at Mass General.

“I think there’s a role for the federal government to take on these initiatives,” Dr. Atlas said. Government intervention could help create “national IT systems to create standards for creating code for what an abnormal result is and how it should be followed,” he said.

While interventions improved patient follow-up, the overall rates were still low.

“What concerns me is that despite the various interventions implemented to encourage and support patients to return for follow-up testing, over 60% of patients still did not return for the recommended testing,” said Joann G. Elmore, MD, MPH, professor of medicine at the University of California, Los Angeles. Dr. Elmore was not involved with the study.

The research took place during the COVID-19 pandemic, which may have reduced follow-up, the study authors wrote. Still, given that previous research has shown that follow-up tends to be low, the rates highlight “the need to understand factors associated with not completing follow-up that go beyond reminder effort,” they wrote. These include a need for patient education about the meaning of test results and what follow-up procedures involve.

The study was supported by the National Cancer Institute and the American Cancer Society. The authors have disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Screening for cancer is only half the battle: Patients often fail to complete recommended follow-up and additional testing after an abnormal result, leaving them at risk, according to authors of a new study published in the Journal of the American Medical Association.

Results from the clustered, randomized clinical trial indicate that systems-based interventions, such as automating reminders in electronic health records (EHRs), outreach in the form of phone calls or letters, and assistance with barriers to health care, such as housing insecurity, can increase the number of patients who complete appropriate diagnostic follow-up after an abnormal result.

Patients who received an EHR reminder, outreach call or letter, and additional calls to screen for and assist with nine barriers to health care – housing insecurity, food insecurity, paying for basic utilities, family caregiving, legal issues, transportation, financial compensation for treatment, education, and employment – completed follow-up within 120 days of study enrollment at a rate of 31.4%. The follow-up rate was 31% for those who received only an EHR reminder and outreach, 22.7% for those who received only an EHR reminder, and 22.9% for those who received usual care.

“The benefits of cancer screening won’t be fully realized without systems to ensure timely follow-up of abnormal results,” said Anna Tosteson, ScD, director of the Dartmouth Institute for Health Policy and Clinical Practice in Lebanon, N.H., a coauthor of the study.

Current payment incentives and quality-of-care indicators focus on getting people in for screening but should also address completion of screening – meaning timely and appropriate follow-up of results that could be indicative of cancer, Dr. Tosteson said.

“There’s a disconnect if you have screening rates that are high but once people have an abnormal result, which is potentially one step closer to a cancer diagnosis, there are no systems in place to help clinicians track them,” said study coauthor Jennifer Haas, MD, director of the Center for Primary Care Research at Massachusetts General Hospital in Boston.

In a 2016 study, researchers found that follow-up rates after abnormal cancer screenings varied widely. While 95.6% of patients with abnormal breast cancer screenings underwent timely follow-up testing, only 68.1% of patients with colorectal abnormalities and 44.8% of patients with cervical abnormalities did so.

Researchers for the new study used guideline recommendations and specialist input to create automated EHR algorithms that determined a follow-up period and diagnostic test.

They put the algorithm into practice with 11,980 patients who were part of 44 primary care practices within three health networks between August 2020 and December 2021. All patients had received abnormal test results for colorectal, breast, cervical, or lung cancer in varying risk categories.

All patients received usual care from their providers, which consisted of a “hodgepodge of whatever their clinic usually does,” Dr. Haas said. Without standards and systems in place for follow-up, the burden of testing and tracking patients with abnormal results typically falls on the primary care provider.

The researchers intervened only when patients were overdue for completion of follow-up. They then staggered the interventions sequentially.

All study participants received an automated, algorithm-triggered EHR reminder for follow-up in their patient portal along with routine health maintenance reminders. To view the reminder, patients had to log into their portal. Participants in the outreach and outreach and navigation groups also received a phone call, an EHR message, or a physical letter 2 weeks after receiving an EHR notification if they hadn’t completed follow-up. Research assistants performed the outreach after having been prompted by the algorithm.

After another 4 weeks, those in the EHR, outreach, and navigation group received a call from a patient navigator who helped them address nine barriers to health care, chiefly by providing them with referrals to free resources.

Among patients who received navigation, outcomes were not significantly better than among those who received EHR and outreach, indicating social determinants of health did not significantly affect the population studied or that the modest approach to navigation and the resources provided were insufficient, Dr. Haas said.

The complexity of an automated platform that encompasses many types of cancers, test results, and other data elements could prove difficult to apply in settings with less infrastructure, said Steven Atlas, MD, MPH, director of the Practice-Based Research and Quality Improvement Network in the division of general internal medicine at Mass General.

“I think there’s a role for the federal government to take on these initiatives,” Dr. Atlas said. Government intervention could help create “national IT systems to create standards for creating code for what an abnormal result is and how it should be followed,” he said.

While interventions improved patient follow-up, the overall rates were still low.

“What concerns me is that despite the various interventions implemented to encourage and support patients to return for follow-up testing, over 60% of patients still did not return for the recommended testing,” said Joann G. Elmore, MD, MPH, professor of medicine at the University of California, Los Angeles. Dr. Elmore was not involved with the study.

The research took place during the COVID-19 pandemic, which may have reduced follow-up, the study authors wrote. Still, given that previous research has shown that follow-up tends to be low, the rates highlight “the need to understand factors associated with not completing follow-up that go beyond reminder effort,” they wrote. These include a need for patient education about the meaning of test results and what follow-up procedures involve.

The study was supported by the National Cancer Institute and the American Cancer Society. The authors have disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Screening for cancer is only half the battle: Patients often fail to complete recommended follow-up and additional testing after an abnormal result, leaving them at risk, according to authors of a new study published in the Journal of the American Medical Association.

Results from the clustered, randomized clinical trial indicate that systems-based interventions, such as automating reminders in electronic health records (EHRs), outreach in the form of phone calls or letters, and assistance with barriers to health care, such as housing insecurity, can increase the number of patients who complete appropriate diagnostic follow-up after an abnormal result.

Patients who received an EHR reminder, outreach call or letter, and additional calls to screen for and assist with nine barriers to health care – housing insecurity, food insecurity, paying for basic utilities, family caregiving, legal issues, transportation, financial compensation for treatment, education, and employment – completed follow-up within 120 days of study enrollment at a rate of 31.4%. The follow-up rate was 31% for those who received only an EHR reminder and outreach, 22.7% for those who received only an EHR reminder, and 22.9% for those who received usual care.

“The benefits of cancer screening won’t be fully realized without systems to ensure timely follow-up of abnormal results,” said Anna Tosteson, ScD, director of the Dartmouth Institute for Health Policy and Clinical Practice in Lebanon, N.H., a coauthor of the study.

Current payment incentives and quality-of-care indicators focus on getting people in for screening but should also address completion of screening – meaning timely and appropriate follow-up of results that could be indicative of cancer, Dr. Tosteson said.

“There’s a disconnect if you have screening rates that are high but once people have an abnormal result, which is potentially one step closer to a cancer diagnosis, there are no systems in place to help clinicians track them,” said study coauthor Jennifer Haas, MD, director of the Center for Primary Care Research at Massachusetts General Hospital in Boston.

In a 2016 study, researchers found that follow-up rates after abnormal cancer screenings varied widely. While 95.6% of patients with abnormal breast cancer screenings underwent timely follow-up testing, only 68.1% of patients with colorectal abnormalities and 44.8% of patients with cervical abnormalities did so.

Researchers for the new study used guideline recommendations and specialist input to create automated EHR algorithms that determined a follow-up period and diagnostic test.

They put the algorithm into practice with 11,980 patients who were part of 44 primary care practices within three health networks between August 2020 and December 2021. All patients had received abnormal test results for colorectal, breast, cervical, or lung cancer in varying risk categories.

All patients received usual care from their providers, which consisted of a “hodgepodge of whatever their clinic usually does,” Dr. Haas said. Without standards and systems in place for follow-up, the burden of testing and tracking patients with abnormal results typically falls on the primary care provider.

The researchers intervened only when patients were overdue for completion of follow-up. They then staggered the interventions sequentially.

All study participants received an automated, algorithm-triggered EHR reminder for follow-up in their patient portal along with routine health maintenance reminders. To view the reminder, patients had to log into their portal. Participants in the outreach and outreach and navigation groups also received a phone call, an EHR message, or a physical letter 2 weeks after receiving an EHR notification if they hadn’t completed follow-up. Research assistants performed the outreach after having been prompted by the algorithm.

After another 4 weeks, those in the EHR, outreach, and navigation group received a call from a patient navigator who helped them address nine barriers to health care, chiefly by providing them with referrals to free resources.

Among patients who received navigation, outcomes were not significantly better than among those who received EHR and outreach, indicating social determinants of health did not significantly affect the population studied or that the modest approach to navigation and the resources provided were insufficient, Dr. Haas said.

The complexity of an automated platform that encompasses many types of cancers, test results, and other data elements could prove difficult to apply in settings with less infrastructure, said Steven Atlas, MD, MPH, director of the Practice-Based Research and Quality Improvement Network in the division of general internal medicine at Mass General.

“I think there’s a role for the federal government to take on these initiatives,” Dr. Atlas said. Government intervention could help create “national IT systems to create standards for creating code for what an abnormal result is and how it should be followed,” he said.

While interventions improved patient follow-up, the overall rates were still low.

“What concerns me is that despite the various interventions implemented to encourage and support patients to return for follow-up testing, over 60% of patients still did not return for the recommended testing,” said Joann G. Elmore, MD, MPH, professor of medicine at the University of California, Los Angeles. Dr. Elmore was not involved with the study.

The research took place during the COVID-19 pandemic, which may have reduced follow-up, the study authors wrote. Still, given that previous research has shown that follow-up tends to be low, the rates highlight “the need to understand factors associated with not completing follow-up that go beyond reminder effort,” they wrote. These include a need for patient education about the meaning of test results and what follow-up procedures involve.

The study was supported by the National Cancer Institute and the American Cancer Society. The authors have disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

SAN DIEGO – Patients with limited-stage small cell lung cancer (LS-SCLC) had improved overall survival and progression-free survival when they received higher-dose thoracic radiotherapy instead of the standard treatment, according to a new multicenter, open-label, randomized phase III trial.

Among 224 patients in China, aged 18-70, those randomly assigned to receive volumetric-modulated arc radiotherapy of high-dose, hypofractionated thoracic radiotherapy of 54 Gy in 30 fractions had a much higher median overall survival (62.4 months) than those who received the standard dose of 45 Gy in 30 fractions (43.1 months, P = .001), reported Jiayi Yu, PhD, of Beijing University Cancer Hospital and Institute and colleagues at the annual meeting of the American Society for Radiation Oncology.

Median progression-free survival was also higher in the 54 Gy group (30.5 months vs. 16.7 months in the 45 Gy group, P = .044).

Kristin Higgins, MD, of Winship Cancer Institute of Emory University, Atlanta, provided perspective at the ASTRO session following Dr. Yu’s presentation. She noted that the study population is quite different than that of LS-SCLC patients in the United States, where patients are often older and more likely to have a history of smoking.

“We need more technical details to understand how to deliver this regimen in clinical practice, and it may not be applicable for all patients,” she said. Still, she added that “a key takeaway here is that optimizing the radiotherapy component of treatment is very important.”

Both groups received chemotherapy. “Higher-dose thoracic radiation therapy concurrently with chemotherapy is an alternative therapeutic option,” Dr. Yu said at an ASTRO presentation.

As Dr. Yu noted, twice-daily thoracic radiotherapy of 45 Gy in 30 fractions and concurrent chemotherapy has been the standard treatment for LS-SCLC for the last 20 years. Trials failed to show benefits for once-daily 66-Gy (33 fractions) or 70-Gy treatment (35 fractions), but a phase 2 trial published in 2023 did indicate that twice-daily treatment of 60 Gy (40 fractions) improved survival without boosting side effects.

For the new study, researchers tracked 224 patients from 2017 to 2021 who were previously untreated or had received specific chemotherapy treatments and had ECOG performance status scores of 0 or 1; 108 patients were randomly assigned to the 54-Gy arm and 116 to the 45-Gy arm. All were recruited at 16 public hospitals in China.

The median age in the two groups were 60 in the 54-Gy arm and 62 in the 45-Gy arm; the percentages of women were similar (45.4% and 45.7%, respectively). Most were current or former smokers (62.0% and 61.2%, respectively).

The researchers closed the trial in April 2021 because of the survival benefit in the 54-Gy arm, and patients were tracked through January 2023 for a median 45 months.

Nearly three-quarters of patients in the 54-Gy arm survived to 2 years (77.7%) vs. 53.4% in the 45-Gy arm, a 41% reduction in risk of death. Adverse events were similar between the groups, with 1 reported treatment-related death (myocardial infarction), in the 54-Gy group.

In an interview, Kenneth Rosenzweig, MD, chairman of the department of radiation oncology at Icahn School of Medicine at Mount Sinai, New York, praised the study. It’s “no surprise” that higher radiation doses are well-tolerated since “our ability to shield normal tissue has improved” over the years, said Dr. Rosenzweig, who served as a moderator of the ASTRO session where the research was presented.

However, he cautioned that hypofractionation is still “intense” and may not be appropriate for certain patients. And he added that some clinics may not be set up to provide twice-daily treatments.

Information about study funding was not provided. The study authors have no disclosures. Dr. Higgins discloses relationships with AstraZeneca and Regeneron (advisory board), Jazz (funded research), and Janssen and Picture Health (consulting). Dr. Rosenzweig has no disclosures.

SAN DIEGO – Patients with limited-stage small cell lung cancer (LS-SCLC) had improved overall survival and progression-free survival when they received higher-dose thoracic radiotherapy instead of the standard treatment, according to a new multicenter, open-label, randomized phase III trial.

Among 224 patients in China, aged 18-70, those randomly assigned to receive volumetric-modulated arc radiotherapy of high-dose, hypofractionated thoracic radiotherapy of 54 Gy in 30 fractions had a much higher median overall survival (62.4 months) than those who received the standard dose of 45 Gy in 30 fractions (43.1 months, P = .001), reported Jiayi Yu, PhD, of Beijing University Cancer Hospital and Institute and colleagues at the annual meeting of the American Society for Radiation Oncology.

Median progression-free survival was also higher in the 54 Gy group (30.5 months vs. 16.7 months in the 45 Gy group, P = .044).

Kristin Higgins, MD, of Winship Cancer Institute of Emory University, Atlanta, provided perspective at the ASTRO session following Dr. Yu’s presentation. She noted that the study population is quite different than that of LS-SCLC patients in the United States, where patients are often older and more likely to have a history of smoking.

“We need more technical details to understand how to deliver this regimen in clinical practice, and it may not be applicable for all patients,” she said. Still, she added that “a key takeaway here is that optimizing the radiotherapy component of treatment is very important.”

Both groups received chemotherapy. “Higher-dose thoracic radiation therapy concurrently with chemotherapy is an alternative therapeutic option,” Dr. Yu said at an ASTRO presentation.

As Dr. Yu noted, twice-daily thoracic radiotherapy of 45 Gy in 30 fractions and concurrent chemotherapy has been the standard treatment for LS-SCLC for the last 20 years. Trials failed to show benefits for once-daily 66-Gy (33 fractions) or 70-Gy treatment (35 fractions), but a phase 2 trial published in 2023 did indicate that twice-daily treatment of 60 Gy (40 fractions) improved survival without boosting side effects.

For the new study, researchers tracked 224 patients from 2017 to 2021 who were previously untreated or had received specific chemotherapy treatments and had ECOG performance status scores of 0 or 1; 108 patients were randomly assigned to the 54-Gy arm and 116 to the 45-Gy arm. All were recruited at 16 public hospitals in China.

The median age in the two groups were 60 in the 54-Gy arm and 62 in the 45-Gy arm; the percentages of women were similar (45.4% and 45.7%, respectively). Most were current or former smokers (62.0% and 61.2%, respectively).

The researchers closed the trial in April 2021 because of the survival benefit in the 54-Gy arm, and patients were tracked through January 2023 for a median 45 months.

Nearly three-quarters of patients in the 54-Gy arm survived to 2 years (77.7%) vs. 53.4% in the 45-Gy arm, a 41% reduction in risk of death. Adverse events were similar between the groups, with 1 reported treatment-related death (myocardial infarction), in the 54-Gy group.

In an interview, Kenneth Rosenzweig, MD, chairman of the department of radiation oncology at Icahn School of Medicine at Mount Sinai, New York, praised the study. It’s “no surprise” that higher radiation doses are well-tolerated since “our ability to shield normal tissue has improved” over the years, said Dr. Rosenzweig, who served as a moderator of the ASTRO session where the research was presented.

However, he cautioned that hypofractionation is still “intense” and may not be appropriate for certain patients. And he added that some clinics may not be set up to provide twice-daily treatments.

Information about study funding was not provided. The study authors have no disclosures. Dr. Higgins discloses relationships with AstraZeneca and Regeneron (advisory board), Jazz (funded research), and Janssen and Picture Health (consulting). Dr. Rosenzweig has no disclosures.

SAN DIEGO – Patients with limited-stage small cell lung cancer (LS-SCLC) had improved overall survival and progression-free survival when they received higher-dose thoracic radiotherapy instead of the standard treatment, according to a new multicenter, open-label, randomized phase III trial.

Among 224 patients in China, aged 18-70, those randomly assigned to receive volumetric-modulated arc radiotherapy of high-dose, hypofractionated thoracic radiotherapy of 54 Gy in 30 fractions had a much higher median overall survival (62.4 months) than those who received the standard dose of 45 Gy in 30 fractions (43.1 months, P = .001), reported Jiayi Yu, PhD, of Beijing University Cancer Hospital and Institute and colleagues at the annual meeting of the American Society for Radiation Oncology.

Median progression-free survival was also higher in the 54 Gy group (30.5 months vs. 16.7 months in the 45 Gy group, P = .044).

Kristin Higgins, MD, of Winship Cancer Institute of Emory University, Atlanta, provided perspective at the ASTRO session following Dr. Yu’s presentation. She noted that the study population is quite different than that of LS-SCLC patients in the United States, where patients are often older and more likely to have a history of smoking.

“We need more technical details to understand how to deliver this regimen in clinical practice, and it may not be applicable for all patients,” she said. Still, she added that “a key takeaway here is that optimizing the radiotherapy component of treatment is very important.”

Both groups received chemotherapy. “Higher-dose thoracic radiation therapy concurrently with chemotherapy is an alternative therapeutic option,” Dr. Yu said at an ASTRO presentation.

As Dr. Yu noted, twice-daily thoracic radiotherapy of 45 Gy in 30 fractions and concurrent chemotherapy has been the standard treatment for LS-SCLC for the last 20 years. Trials failed to show benefits for once-daily 66-Gy (33 fractions) or 70-Gy treatment (35 fractions), but a phase 2 trial published in 2023 did indicate that twice-daily treatment of 60 Gy (40 fractions) improved survival without boosting side effects.

For the new study, researchers tracked 224 patients from 2017 to 2021 who were previously untreated or had received specific chemotherapy treatments and had ECOG performance status scores of 0 or 1; 108 patients were randomly assigned to the 54-Gy arm and 116 to the 45-Gy arm. All were recruited at 16 public hospitals in China.

The median age in the two groups were 60 in the 54-Gy arm and 62 in the 45-Gy arm; the percentages of women were similar (45.4% and 45.7%, respectively). Most were current or former smokers (62.0% and 61.2%, respectively).

The researchers closed the trial in April 2021 because of the survival benefit in the 54-Gy arm, and patients were tracked through January 2023 for a median 45 months.

Nearly three-quarters of patients in the 54-Gy arm survived to 2 years (77.7%) vs. 53.4% in the 45-Gy arm, a 41% reduction in risk of death. Adverse events were similar between the groups, with 1 reported treatment-related death (myocardial infarction), in the 54-Gy group.

In an interview, Kenneth Rosenzweig, MD, chairman of the department of radiation oncology at Icahn School of Medicine at Mount Sinai, New York, praised the study. It’s “no surprise” that higher radiation doses are well-tolerated since “our ability to shield normal tissue has improved” over the years, said Dr. Rosenzweig, who served as a moderator of the ASTRO session where the research was presented.

However, he cautioned that hypofractionation is still “intense” and may not be appropriate for certain patients. And he added that some clinics may not be set up to provide twice-daily treatments.

Information about study funding was not provided. The study authors have no disclosures. Dr. Higgins discloses relationships with AstraZeneca and Regeneron (advisory board), Jazz (funded research), and Janssen and Picture Health (consulting). Dr. Rosenzweig has no disclosures.