Lung Cancer

Despite Spain’s lack of a national project or standard protocol for biomarker testing, more than half of patients diagnosed with stage 4 non–small cell lung cancer (NSCLC) are tested for biomarkers, according to a Spanish national registry study reported at the 2022 European Lung Cancer Congress.

“In recent years we’ve developed drugs that target biomarkers, so it’s important to identify those biomarkers to guide treatment and have an impact on the survival of our patients,” said lead author Virginia Calvo, MD, a medical oncologist with the Puerta de Hierro Majadahonda University Hospital, Madrid.

“If we don’t know our patients’ biomarkers, we can’t treat them with targeted therapies,” she added, noting that the overall survival of lung cancer patients has increased by 15% in the last 10 years, largely because of better therapies such as targeted drugs for advanced stage disease and immunotherapies.

To assess the status of biomarker testing in Spain, Dr. Calvo and colleagues analyzed data from the country’s Thoracic Tumor Registry on 9,239 patients diagnosed with metastatic NSCLC from 2016 to the present, 7,467 (81%) with nonsquamous tumors and 1,772 (19%) with squamous tumors.

They found that 85% of patients with nonsquamous NSCLC and about 53% of those with squamous cancers had undergone biomarker testing. They discovered that 4,115 (44%) of patients tested positive for EGFR, ALK, KRAS, BRAF, ROS1, or PD-L1.

Dr. Calvo attributes the widespread use of biomarker testing and its significant increase in the last 5 years to the growing knowledge and understanding of the disease.

“We are learning more about NSCLC, and I think in the next few years the number of biomarkers are going to grow,” she said.

The study’s findings also highlight the importance of establishing and maintaining cancer registries, Dr. Calvo said, noting that 182 hospitals across Spain and more than 550 experts participate in the Thoracic Tumors Registry, which includes data on patients from every Spanish territory.

“It’s important to collect information on real-life cancer care so that we know what our real situation is and take steps to improve it,” she said.

She anticipates that treatment for NSCLC patients will become increasingly complex in the future with the growing number of different biomarkers and the proportion of patients who test positive for them. “We may need to establish national strategies to implement next generation sequencing so that we can identify different biomarkers and improve the survival of our patients.”

In a press release, Rolf Stahel, MD, president of the European Thoracic Oncology Platform, said that it would be helpful to look at how frequently molecular testing led to patients receiving appropriate targeted treatment.

In the United States, the National Comprehensive Cancer Network recommends biomarker testing for eligible patients with newly diagnosed stage 4 NSCLC, and it can be considered for patients with squamous histology because 5%-10% of these tumors have targetable mutations. “This is because numerous lines of evidence show that patients with stage 4 NSCLC and a targetable mutation, typically have improved overall survival when treated with a targeted therapy,” wrote the authors of the NCCN recommendations.

“For newly diagnosed stage 4 NSCLC, there is always a tension between the need to start therapy versus waiting for molecular results. This is because if a recommended targeted option is identified, it is the optimal first-line therapy. Targeted therapy cannot be given to everyone. Different biomarkers predict response to different agents. This has been well illustrated and it makes testing critically important for patients with NSCLC,” Dara Aisner, MD, PhD, associate professor of pathology with the University of Colorado at Denver, Aurora, wrote in the NCCN guideline.

The study presented at ELCC was funded by a grant from the European Union’s Horizon 2020 Research and Innovation Program. Dr. Calvo has received fees from Roche, Bristol-Myers Squibb, MSD and AstraZeneca.

Despite Spain’s lack of a national project or standard protocol for biomarker testing, more than half of patients diagnosed with stage 4 non–small cell lung cancer (NSCLC) are tested for biomarkers, according to a Spanish national registry study reported at the 2022 European Lung Cancer Congress.

“In recent years we’ve developed drugs that target biomarkers, so it’s important to identify those biomarkers to guide treatment and have an impact on the survival of our patients,” said lead author Virginia Calvo, MD, a medical oncologist with the Puerta de Hierro Majadahonda University Hospital, Madrid.

“If we don’t know our patients’ biomarkers, we can’t treat them with targeted therapies,” she added, noting that the overall survival of lung cancer patients has increased by 15% in the last 10 years, largely because of better therapies such as targeted drugs for advanced stage disease and immunotherapies.

To assess the status of biomarker testing in Spain, Dr. Calvo and colleagues analyzed data from the country’s Thoracic Tumor Registry on 9,239 patients diagnosed with metastatic NSCLC from 2016 to the present, 7,467 (81%) with nonsquamous tumors and 1,772 (19%) with squamous tumors.

They found that 85% of patients with nonsquamous NSCLC and about 53% of those with squamous cancers had undergone biomarker testing. They discovered that 4,115 (44%) of patients tested positive for EGFR, ALK, KRAS, BRAF, ROS1, or PD-L1.

Dr. Calvo attributes the widespread use of biomarker testing and its significant increase in the last 5 years to the growing knowledge and understanding of the disease.

“We are learning more about NSCLC, and I think in the next few years the number of biomarkers are going to grow,” she said.

The study’s findings also highlight the importance of establishing and maintaining cancer registries, Dr. Calvo said, noting that 182 hospitals across Spain and more than 550 experts participate in the Thoracic Tumors Registry, which includes data on patients from every Spanish territory.

“It’s important to collect information on real-life cancer care so that we know what our real situation is and take steps to improve it,” she said.

She anticipates that treatment for NSCLC patients will become increasingly complex in the future with the growing number of different biomarkers and the proportion of patients who test positive for them. “We may need to establish national strategies to implement next generation sequencing so that we can identify different biomarkers and improve the survival of our patients.”

In a press release, Rolf Stahel, MD, president of the European Thoracic Oncology Platform, said that it would be helpful to look at how frequently molecular testing led to patients receiving appropriate targeted treatment.

In the United States, the National Comprehensive Cancer Network recommends biomarker testing for eligible patients with newly diagnosed stage 4 NSCLC, and it can be considered for patients with squamous histology because 5%-10% of these tumors have targetable mutations. “This is because numerous lines of evidence show that patients with stage 4 NSCLC and a targetable mutation, typically have improved overall survival when treated with a targeted therapy,” wrote the authors of the NCCN recommendations.

“For newly diagnosed stage 4 NSCLC, there is always a tension between the need to start therapy versus waiting for molecular results. This is because if a recommended targeted option is identified, it is the optimal first-line therapy. Targeted therapy cannot be given to everyone. Different biomarkers predict response to different agents. This has been well illustrated and it makes testing critically important for patients with NSCLC,” Dara Aisner, MD, PhD, associate professor of pathology with the University of Colorado at Denver, Aurora, wrote in the NCCN guideline.

The study presented at ELCC was funded by a grant from the European Union’s Horizon 2020 Research and Innovation Program. Dr. Calvo has received fees from Roche, Bristol-Myers Squibb, MSD and AstraZeneca.

Despite Spain’s lack of a national project or standard protocol for biomarker testing, more than half of patients diagnosed with stage 4 non–small cell lung cancer (NSCLC) are tested for biomarkers, according to a Spanish national registry study reported at the 2022 European Lung Cancer Congress.

“In recent years we’ve developed drugs that target biomarkers, so it’s important to identify those biomarkers to guide treatment and have an impact on the survival of our patients,” said lead author Virginia Calvo, MD, a medical oncologist with the Puerta de Hierro Majadahonda University Hospital, Madrid.

“If we don’t know our patients’ biomarkers, we can’t treat them with targeted therapies,” she added, noting that the overall survival of lung cancer patients has increased by 15% in the last 10 years, largely because of better therapies such as targeted drugs for advanced stage disease and immunotherapies.

To assess the status of biomarker testing in Spain, Dr. Calvo and colleagues analyzed data from the country’s Thoracic Tumor Registry on 9,239 patients diagnosed with metastatic NSCLC from 2016 to the present, 7,467 (81%) with nonsquamous tumors and 1,772 (19%) with squamous tumors.

They found that 85% of patients with nonsquamous NSCLC and about 53% of those with squamous cancers had undergone biomarker testing. They discovered that 4,115 (44%) of patients tested positive for EGFR, ALK, KRAS, BRAF, ROS1, or PD-L1.

Dr. Calvo attributes the widespread use of biomarker testing and its significant increase in the last 5 years to the growing knowledge and understanding of the disease.

“We are learning more about NSCLC, and I think in the next few years the number of biomarkers are going to grow,” she said.

The study’s findings also highlight the importance of establishing and maintaining cancer registries, Dr. Calvo said, noting that 182 hospitals across Spain and more than 550 experts participate in the Thoracic Tumors Registry, which includes data on patients from every Spanish territory.

“It’s important to collect information on real-life cancer care so that we know what our real situation is and take steps to improve it,” she said.

She anticipates that treatment for NSCLC patients will become increasingly complex in the future with the growing number of different biomarkers and the proportion of patients who test positive for them. “We may need to establish national strategies to implement next generation sequencing so that we can identify different biomarkers and improve the survival of our patients.”

In a press release, Rolf Stahel, MD, president of the European Thoracic Oncology Platform, said that it would be helpful to look at how frequently molecular testing led to patients receiving appropriate targeted treatment.

In the United States, the National Comprehensive Cancer Network recommends biomarker testing for eligible patients with newly diagnosed stage 4 NSCLC, and it can be considered for patients with squamous histology because 5%-10% of these tumors have targetable mutations. “This is because numerous lines of evidence show that patients with stage 4 NSCLC and a targetable mutation, typically have improved overall survival when treated with a targeted therapy,” wrote the authors of the NCCN recommendations.

“For newly diagnosed stage 4 NSCLC, there is always a tension between the need to start therapy versus waiting for molecular results. This is because if a recommended targeted option is identified, it is the optimal first-line therapy. Targeted therapy cannot be given to everyone. Different biomarkers predict response to different agents. This has been well illustrated and it makes testing critically important for patients with NSCLC,” Dara Aisner, MD, PhD, associate professor of pathology with the University of Colorado at Denver, Aurora, wrote in the NCCN guideline.

The study presented at ELCC was funded by a grant from the European Union’s Horizon 2020 Research and Innovation Program. Dr. Calvo has received fees from Roche, Bristol-Myers Squibb, MSD and AstraZeneca.

Metformin use, regardless of dose, was associated with increased overall survival in older adults with advanced cancer, according to results of a retrospective study of patients with type 2 diabetes and stage IV cancer.

The analysis included 7,725 patients with lung, breast, colorectal, prostate, or pancreatic cancer identified through a search of a Surveillance, Epidemiology, and End Results (SEER)-Medicare dataset from 2007 to 2016.

Out of the full dataset, 2,981 patients (38.5%) had been prescribed metformin, and use was highest among patients with prostate cancer (46%).

Patients who took metformin versus those who did not had significantly better overall survival in both unadjusted (unadjusted hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.69-0.76; P < .001) and adjusted models (adjusted HR, 0.77; 95% CI, 0.73-0.81; P < .001).

Lead author Lisa Scarton, PhD, RN, assistant professor, University of Florida College of Nursing, Gainesville, said that the “underlying mechanisms of metformin related to cancer are still not completely understood,” but many studies have shown metformin is associated with a reduction in the incidence of cancer, a reduction in cancer mortality, and an improvement in overall survival.

“As more evidence of anticancer benefit of metformin is emerging, it is important to explore optimal dosages that significantly improve cancer outcomes to boost anticancer effect,” she said in an interview.  

Dr. Scarton presented the new data in a poster at the annual meeting of the American Association for Cancer Research.  

The analysis found no significant difference in overall survival between patients who took metformin with average daily doses ≥ 1,000 mg or < 1,000 mg (aHR, 1.00; 95% CI, 0.93-1.08; P = .90).

Although the improvement in overall survival was seen in cancer subgroups, regardless of dose, Dr. Scarton noted the benefit was greatest among patients with breast cancer (aHR, 0.67; 95% CI, 0.56-0.82; P < .001). Hazard ratios among those who received metformin were 0.78 (95% CI, 0.69-0.88; P < .001) for colorectal cancer, 0.77 (95% CI, 0.72-0.82; P < .001) for lung cancer, 0.82 (95% CI, 0.72-0.93; P < .001) for pancreatic cancer, and 0.74 (95% CI, 0.62-0.88; P = .002) for prostate cancer. Also, she noted that race/ethnicity did not play a role as a significant factor for predicting better overall survival.

Among study limitations, Dr. Scarton said, was the advanced age of patients. “Our study population was 66 and older. It would be interesting to investigate this relationship among younger adults. We would also explore explicit benefits of metformin use in different racial and ethnic groups.”

The study was funded by the University of Florida. Dr. Scarton has reported no relevant financial relationships.

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

Metformin use, regardless of dose, was associated with increased overall survival in older adults with advanced cancer, according to results of a retrospective study of patients with type 2 diabetes and stage IV cancer.

The analysis included 7,725 patients with lung, breast, colorectal, prostate, or pancreatic cancer identified through a search of a Surveillance, Epidemiology, and End Results (SEER)-Medicare dataset from 2007 to 2016.

Out of the full dataset, 2,981 patients (38.5%) had been prescribed metformin, and use was highest among patients with prostate cancer (46%).

Patients who took metformin versus those who did not had significantly better overall survival in both unadjusted (unadjusted hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.69-0.76; P < .001) and adjusted models (adjusted HR, 0.77; 95% CI, 0.73-0.81; P < .001).

Lead author Lisa Scarton, PhD, RN, assistant professor, University of Florida College of Nursing, Gainesville, said that the “underlying mechanisms of metformin related to cancer are still not completely understood,” but many studies have shown metformin is associated with a reduction in the incidence of cancer, a reduction in cancer mortality, and an improvement in overall survival.

“As more evidence of anticancer benefit of metformin is emerging, it is important to explore optimal dosages that significantly improve cancer outcomes to boost anticancer effect,” she said in an interview.  

Dr. Scarton presented the new data in a poster at the annual meeting of the American Association for Cancer Research.  

The analysis found no significant difference in overall survival between patients who took metformin with average daily doses ≥ 1,000 mg or < 1,000 mg (aHR, 1.00; 95% CI, 0.93-1.08; P = .90).

Although the improvement in overall survival was seen in cancer subgroups, regardless of dose, Dr. Scarton noted the benefit was greatest among patients with breast cancer (aHR, 0.67; 95% CI, 0.56-0.82; P < .001). Hazard ratios among those who received metformin were 0.78 (95% CI, 0.69-0.88; P < .001) for colorectal cancer, 0.77 (95% CI, 0.72-0.82; P < .001) for lung cancer, 0.82 (95% CI, 0.72-0.93; P < .001) for pancreatic cancer, and 0.74 (95% CI, 0.62-0.88; P = .002) for prostate cancer. Also, she noted that race/ethnicity did not play a role as a significant factor for predicting better overall survival.

Among study limitations, Dr. Scarton said, was the advanced age of patients. “Our study population was 66 and older. It would be interesting to investigate this relationship among younger adults. We would also explore explicit benefits of metformin use in different racial and ethnic groups.”

The study was funded by the University of Florida. Dr. Scarton has reported no relevant financial relationships.

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

Metformin use, regardless of dose, was associated with increased overall survival in older adults with advanced cancer, according to results of a retrospective study of patients with type 2 diabetes and stage IV cancer.

The analysis included 7,725 patients with lung, breast, colorectal, prostate, or pancreatic cancer identified through a search of a Surveillance, Epidemiology, and End Results (SEER)-Medicare dataset from 2007 to 2016.

Out of the full dataset, 2,981 patients (38.5%) had been prescribed metformin, and use was highest among patients with prostate cancer (46%).

Patients who took metformin versus those who did not had significantly better overall survival in both unadjusted (unadjusted hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.69-0.76; P < .001) and adjusted models (adjusted HR, 0.77; 95% CI, 0.73-0.81; P < .001).

Lead author Lisa Scarton, PhD, RN, assistant professor, University of Florida College of Nursing, Gainesville, said that the “underlying mechanisms of metformin related to cancer are still not completely understood,” but many studies have shown metformin is associated with a reduction in the incidence of cancer, a reduction in cancer mortality, and an improvement in overall survival.

“As more evidence of anticancer benefit of metformin is emerging, it is important to explore optimal dosages that significantly improve cancer outcomes to boost anticancer effect,” she said in an interview.  

Dr. Scarton presented the new data in a poster at the annual meeting of the American Association for Cancer Research.  

The analysis found no significant difference in overall survival between patients who took metformin with average daily doses ≥ 1,000 mg or < 1,000 mg (aHR, 1.00; 95% CI, 0.93-1.08; P = .90).

Although the improvement in overall survival was seen in cancer subgroups, regardless of dose, Dr. Scarton noted the benefit was greatest among patients with breast cancer (aHR, 0.67; 95% CI, 0.56-0.82; P < .001). Hazard ratios among those who received metformin were 0.78 (95% CI, 0.69-0.88; P < .001) for colorectal cancer, 0.77 (95% CI, 0.72-0.82; P < .001) for lung cancer, 0.82 (95% CI, 0.72-0.93; P < .001) for pancreatic cancer, and 0.74 (95% CI, 0.62-0.88; P = .002) for prostate cancer. Also, she noted that race/ethnicity did not play a role as a significant factor for predicting better overall survival.

Among study limitations, Dr. Scarton said, was the advanced age of patients. “Our study population was 66 and older. It would be interesting to investigate this relationship among younger adults. We would also explore explicit benefits of metformin use in different racial and ethnic groups.”

The study was funded by the University of Florida. Dr. Scarton has reported no relevant financial relationships.

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

In recent years, patients with advanced lung cancer have benefited from the advent of immune therapies and genotype-directed therapies –both of which have led to improved survival rates. But what will lung cancer look like in 2030?

Pasi A. Janne, MD, PhD, of the Dana-Farber Cancer Institute, Boston, hopes to see improved access to tumor and blood-based genotyping.

Dr. Janne, who serves as director of the Lowe Center for Thoracic Oncology at Dana-Farber, gave a keynote presentation at the 2022 European Lung Cancer Congress, where he highlighted the need to broaden the scope of targeted therapies, make “great drugs work even better,” improve the ability to treat patients based on risk level, and expand the use of targeted therapies in the adjuvant and neoadjuvant setting to make significant progress in the treatment lung cancer treatment in coming years.

Genotyping is underutilized, he said. A 2019 multicenter study reported at the annual meeting of the American Society of Clinical Oncology showed that only 54% of 1,203 patients underwent testing for EGFR mutations, 22% were tested for EGFR, ALK, ROS1, and BRAF mutations, and only 7% were tested for all biomarkers recommended by National Comprehensive Cancer Network guidelines at the time.

That study also showed that only 45% of patients received biomarker-driven treatment, even when driver mutations were detected.

“Immunotherapy was often prescribed instead of targeted therapy, even when molecular results were available,” Dr. Janne said.

Another study, reported at the 2021 ASCO annual meeting, showed some improvement in testing rates, but still, only 37% of patients were tested for all biomarkers as recommended.

Racial disparities in testing have also been observed. Bruno and colleagues found that any next-generation sequencing was performed in 50.1% of White patients, compared with 39.8% of black patients, and NGS prior to first-line therapy was performed in 35.5% and 25.8%, respectively.

The study, also reported at ASCO in 2021, showed that trial participation was observed among 3.9% of White patients and 1.9% of Black patients.

“The studies really highlight the need for increased testing rates and appropriate utilization of testing results to deliver optimal care to our patients with advanced lung cancer. We have a long way to go. To live the promise and appreciate the promise of precision therapy ... we need to be able to offer this testing to all of our patients with lung cancer,” he said.

Dr. Janne reported relationships with numerous pharmaceutical companies, including consulting, research support and stock ownership. He also receives postmarketing royalties from Dana-Farber Cancer Institute–owned intellectual property on EGFR mutations.

In recent years, patients with advanced lung cancer have benefited from the advent of immune therapies and genotype-directed therapies –both of which have led to improved survival rates. But what will lung cancer look like in 2030?

Pasi A. Janne, MD, PhD, of the Dana-Farber Cancer Institute, Boston, hopes to see improved access to tumor and blood-based genotyping.

Dr. Janne, who serves as director of the Lowe Center for Thoracic Oncology at Dana-Farber, gave a keynote presentation at the 2022 European Lung Cancer Congress, where he highlighted the need to broaden the scope of targeted therapies, make “great drugs work even better,” improve the ability to treat patients based on risk level, and expand the use of targeted therapies in the adjuvant and neoadjuvant setting to make significant progress in the treatment lung cancer treatment in coming years.

Genotyping is underutilized, he said. A 2019 multicenter study reported at the annual meeting of the American Society of Clinical Oncology showed that only 54% of 1,203 patients underwent testing for EGFR mutations, 22% were tested for EGFR, ALK, ROS1, and BRAF mutations, and only 7% were tested for all biomarkers recommended by National Comprehensive Cancer Network guidelines at the time.

That study also showed that only 45% of patients received biomarker-driven treatment, even when driver mutations were detected.

“Immunotherapy was often prescribed instead of targeted therapy, even when molecular results were available,” Dr. Janne said.

Another study, reported at the 2021 ASCO annual meeting, showed some improvement in testing rates, but still, only 37% of patients were tested for all biomarkers as recommended.

Racial disparities in testing have also been observed. Bruno and colleagues found that any next-generation sequencing was performed in 50.1% of White patients, compared with 39.8% of black patients, and NGS prior to first-line therapy was performed in 35.5% and 25.8%, respectively.

The study, also reported at ASCO in 2021, showed that trial participation was observed among 3.9% of White patients and 1.9% of Black patients.

“The studies really highlight the need for increased testing rates and appropriate utilization of testing results to deliver optimal care to our patients with advanced lung cancer. We have a long way to go. To live the promise and appreciate the promise of precision therapy ... we need to be able to offer this testing to all of our patients with lung cancer,” he said.

Dr. Janne reported relationships with numerous pharmaceutical companies, including consulting, research support and stock ownership. He also receives postmarketing royalties from Dana-Farber Cancer Institute–owned intellectual property on EGFR mutations.

In recent years, patients with advanced lung cancer have benefited from the advent of immune therapies and genotype-directed therapies –both of which have led to improved survival rates. But what will lung cancer look like in 2030?

Pasi A. Janne, MD, PhD, of the Dana-Farber Cancer Institute, Boston, hopes to see improved access to tumor and blood-based genotyping.

Dr. Janne, who serves as director of the Lowe Center for Thoracic Oncology at Dana-Farber, gave a keynote presentation at the 2022 European Lung Cancer Congress, where he highlighted the need to broaden the scope of targeted therapies, make “great drugs work even better,” improve the ability to treat patients based on risk level, and expand the use of targeted therapies in the adjuvant and neoadjuvant setting to make significant progress in the treatment lung cancer treatment in coming years.

Genotyping is underutilized, he said. A 2019 multicenter study reported at the annual meeting of the American Society of Clinical Oncology showed that only 54% of 1,203 patients underwent testing for EGFR mutations, 22% were tested for EGFR, ALK, ROS1, and BRAF mutations, and only 7% were tested for all biomarkers recommended by National Comprehensive Cancer Network guidelines at the time.

That study also showed that only 45% of patients received biomarker-driven treatment, even when driver mutations were detected.

“Immunotherapy was often prescribed instead of targeted therapy, even when molecular results were available,” Dr. Janne said.

Another study, reported at the 2021 ASCO annual meeting, showed some improvement in testing rates, but still, only 37% of patients were tested for all biomarkers as recommended.

Racial disparities in testing have also been observed. Bruno and colleagues found that any next-generation sequencing was performed in 50.1% of White patients, compared with 39.8% of black patients, and NGS prior to first-line therapy was performed in 35.5% and 25.8%, respectively.

The study, also reported at ASCO in 2021, showed that trial participation was observed among 3.9% of White patients and 1.9% of Black patients.

“The studies really highlight the need for increased testing rates and appropriate utilization of testing results to deliver optimal care to our patients with advanced lung cancer. We have a long way to go. To live the promise and appreciate the promise of precision therapy ... we need to be able to offer this testing to all of our patients with lung cancer,” he said.

Dr. Janne reported relationships with numerous pharmaceutical companies, including consulting, research support and stock ownership. He also receives postmarketing royalties from Dana-Farber Cancer Institute–owned intellectual property on EGFR mutations.

Pathological response has emerged as a valuable endpoint and surrogate marker for overall survival in lung cancer studies, but much work remains to be done, said William D. Travis, MD, director of thoracic pathology at Memorial Sloan Kettering Cancer Center, New York.

In a keynote address at the 2022 European Lung Cancer Conference, Dr. Travis highlighted advances in the use of pathological response in this setting and outlined areas that need refinement. “Pathologic response after preoperative therapy is important because the extent of pathologic response strongly correlates with improved overall survival, and it is reflective of neoadjuvant therapy. The degree of response is associated with the degree of benefit in survival, and it’s being used as a surrogate for survival in phase 2 and 3 neoadjuvant clinical trials.”

In fact, multiple studies have demonstrated that non–small cell lung cancer patients with 10% or less viable residual tumor after treatment have improved overall survival and disease-free survival, compared with patients who have more residual tumor, he explained.

Recent studies have demonstrated the value of pathological response as an endpoint in the neoadjuvant therapy and molecular targeted therapy setting, he said, citing a study published in the Journal of Clinical Oncology that showed major pathological response rates of 14%-45% and pathological complete response rates up to 29% in patients treated with single-agent checkpoint inhibition.

In the CheckMate 816 trial, both major pathologic response and pathological complete response were significantly higher in patients treated with combination nivolumab and chemotherapy, compared with those treated with chemotherapy alone (37% vs. 8.9% and 24% vs. 2%, respectively).

“This high rate of responses with combined immunotherapy and chemotherapy is quite exciting,” he said.

Dr. Travis also stressed the importance of consulting the current International Association for the Study of Lung Cancer Recommendations for Pathologic Assessment of Lung Cancer Resection Specimens After Neoadjuvant Therapy.

He highlighted several key points regarding pathological response in lung cancer:

• Major pathological response (MPR) is calculated as the estimated size of viable tumor divided by the size of the tumor bed.
• Optimal cutoffs for determining MPR is currently 10%, but recent data suggest that in the conventional chemotherapy setting this may vary by tumor histology, with much higher cutoffs of about 65% for adenocarcinoma.
• Estimating the amount of viable tumor is “quite complicated and requires quite a number of steps,” and one the most important steps is “for the surgeon to the pathologist know that given specimen is from a patient who received neoadjuvant therapy.”
• Determining the border of the tumor bed can be challenging, therefore “resection specimens after neoadjuvant therapy should be sampled to optimize comprehensive gross and histologic assessment of the lung tumor bed for pathologic response ... as outlined in the guidelines.”
• The IASLC panel determined that having a single approach for estimating treatment effect would be best, despite the different therapy types and combinations used, but “it is recognized that there may be certain types of features that need to be addressed,” such as immune cell infiltrates in pats who received immunotherapy.
• The recommendations provide specific guidance for measuring tumor size for staging, including for special circumstances.

As for future direction, Dr. Travis said, “one question is how to assess treatment effect in lymph node samples.

“This is done for lymph nodes in breast cancer but not in lung cancer. We need system[s] for lung cancer.”

Good “infrastructure for pathology departments” is needed to support clinical trials, he said, noting that the team at Memorial Sloan Kettering Cancer Center includes physician assistants, tissue procurement staff, frozen section techs, research fellows, and research assistants.

Future work should also aim to standardize pathology assessment for clinical trials, improve the current recommendations, make use of new technology like artificial intelligence, optimize banking protocols and special techniques, and identify radiologic-pathological correlations, he said.

He added that “IASLC is promoting the design and implementation of an international database to collect uniformly clinical and pathologic information with the ultimate goal of fostering collaboration and to facilitate the identification of surrogate endpoints of long-term survival.”

Dr. Travis is a nonpaid pathology consultant for the LCMC3 and LCMC4 trials.

Pathological response has emerged as a valuable endpoint and surrogate marker for overall survival in lung cancer studies, but much work remains to be done, said William D. Travis, MD, director of thoracic pathology at Memorial Sloan Kettering Cancer Center, New York.

In a keynote address at the 2022 European Lung Cancer Conference, Dr. Travis highlighted advances in the use of pathological response in this setting and outlined areas that need refinement. “Pathologic response after preoperative therapy is important because the extent of pathologic response strongly correlates with improved overall survival, and it is reflective of neoadjuvant therapy. The degree of response is associated with the degree of benefit in survival, and it’s being used as a surrogate for survival in phase 2 and 3 neoadjuvant clinical trials.”

In fact, multiple studies have demonstrated that non–small cell lung cancer patients with 10% or less viable residual tumor after treatment have improved overall survival and disease-free survival, compared with patients who have more residual tumor, he explained.

Recent studies have demonstrated the value of pathological response as an endpoint in the neoadjuvant therapy and molecular targeted therapy setting, he said, citing a study published in the Journal of Clinical Oncology that showed major pathological response rates of 14%-45% and pathological complete response rates up to 29% in patients treated with single-agent checkpoint inhibition.

In the CheckMate 816 trial, both major pathologic response and pathological complete response were significantly higher in patients treated with combination nivolumab and chemotherapy, compared with those treated with chemotherapy alone (37% vs. 8.9% and 24% vs. 2%, respectively).

“This high rate of responses with combined immunotherapy and chemotherapy is quite exciting,” he said.

Dr. Travis also stressed the importance of consulting the current International Association for the Study of Lung Cancer Recommendations for Pathologic Assessment of Lung Cancer Resection Specimens After Neoadjuvant Therapy.

He highlighted several key points regarding pathological response in lung cancer:

• Major pathological response (MPR) is calculated as the estimated size of viable tumor divided by the size of the tumor bed.
• Optimal cutoffs for determining MPR is currently 10%, but recent data suggest that in the conventional chemotherapy setting this may vary by tumor histology, with much higher cutoffs of about 65% for adenocarcinoma.
• Estimating the amount of viable tumor is “quite complicated and requires quite a number of steps,” and one the most important steps is “for the surgeon to the pathologist know that given specimen is from a patient who received neoadjuvant therapy.”
• Determining the border of the tumor bed can be challenging, therefore “resection specimens after neoadjuvant therapy should be sampled to optimize comprehensive gross and histologic assessment of the lung tumor bed for pathologic response ... as outlined in the guidelines.”
• The IASLC panel determined that having a single approach for estimating treatment effect would be best, despite the different therapy types and combinations used, but “it is recognized that there may be certain types of features that need to be addressed,” such as immune cell infiltrates in pats who received immunotherapy.
• The recommendations provide specific guidance for measuring tumor size for staging, including for special circumstances.

As for future direction, Dr. Travis said, “one question is how to assess treatment effect in lymph node samples.

“This is done for lymph nodes in breast cancer but not in lung cancer. We need system[s] for lung cancer.”

Good “infrastructure for pathology departments” is needed to support clinical trials, he said, noting that the team at Memorial Sloan Kettering Cancer Center includes physician assistants, tissue procurement staff, frozen section techs, research fellows, and research assistants.

Future work should also aim to standardize pathology assessment for clinical trials, improve the current recommendations, make use of new technology like artificial intelligence, optimize banking protocols and special techniques, and identify radiologic-pathological correlations, he said.

He added that “IASLC is promoting the design and implementation of an international database to collect uniformly clinical and pathologic information with the ultimate goal of fostering collaboration and to facilitate the identification of surrogate endpoints of long-term survival.”

Dr. Travis is a nonpaid pathology consultant for the LCMC3 and LCMC4 trials.

Pathological response has emerged as a valuable endpoint and surrogate marker for overall survival in lung cancer studies, but much work remains to be done, said William D. Travis, MD, director of thoracic pathology at Memorial Sloan Kettering Cancer Center, New York.

In a keynote address at the 2022 European Lung Cancer Conference, Dr. Travis highlighted advances in the use of pathological response in this setting and outlined areas that need refinement. “Pathologic response after preoperative therapy is important because the extent of pathologic response strongly correlates with improved overall survival, and it is reflective of neoadjuvant therapy. The degree of response is associated with the degree of benefit in survival, and it’s being used as a surrogate for survival in phase 2 and 3 neoadjuvant clinical trials.”

In fact, multiple studies have demonstrated that non–small cell lung cancer patients with 10% or less viable residual tumor after treatment have improved overall survival and disease-free survival, compared with patients who have more residual tumor, he explained.

Recent studies have demonstrated the value of pathological response as an endpoint in the neoadjuvant therapy and molecular targeted therapy setting, he said, citing a study published in the Journal of Clinical Oncology that showed major pathological response rates of 14%-45% and pathological complete response rates up to 29% in patients treated with single-agent checkpoint inhibition.

In the CheckMate 816 trial, both major pathologic response and pathological complete response were significantly higher in patients treated with combination nivolumab and chemotherapy, compared with those treated with chemotherapy alone (37% vs. 8.9% and 24% vs. 2%, respectively).

“This high rate of responses with combined immunotherapy and chemotherapy is quite exciting,” he said.

Dr. Travis also stressed the importance of consulting the current International Association for the Study of Lung Cancer Recommendations for Pathologic Assessment of Lung Cancer Resection Specimens After Neoadjuvant Therapy.

He highlighted several key points regarding pathological response in lung cancer:

• Major pathological response (MPR) is calculated as the estimated size of viable tumor divided by the size of the tumor bed.
• Optimal cutoffs for determining MPR is currently 10%, but recent data suggest that in the conventional chemotherapy setting this may vary by tumor histology, with much higher cutoffs of about 65% for adenocarcinoma.
• Estimating the amount of viable tumor is “quite complicated and requires quite a number of steps,” and one the most important steps is “for the surgeon to the pathologist know that given specimen is from a patient who received neoadjuvant therapy.”
• Determining the border of the tumor bed can be challenging, therefore “resection specimens after neoadjuvant therapy should be sampled to optimize comprehensive gross and histologic assessment of the lung tumor bed for pathologic response ... as outlined in the guidelines.”
• The IASLC panel determined that having a single approach for estimating treatment effect would be best, despite the different therapy types and combinations used, but “it is recognized that there may be certain types of features that need to be addressed,” such as immune cell infiltrates in pats who received immunotherapy.
• The recommendations provide specific guidance for measuring tumor size for staging, including for special circumstances.

As for future direction, Dr. Travis said, “one question is how to assess treatment effect in lymph node samples.

“This is done for lymph nodes in breast cancer but not in lung cancer. We need system[s] for lung cancer.”

Good “infrastructure for pathology departments” is needed to support clinical trials, he said, noting that the team at Memorial Sloan Kettering Cancer Center includes physician assistants, tissue procurement staff, frozen section techs, research fellows, and research assistants.

Future work should also aim to standardize pathology assessment for clinical trials, improve the current recommendations, make use of new technology like artificial intelligence, optimize banking protocols and special techniques, and identify radiologic-pathological correlations, he said.

He added that “IASLC is promoting the design and implementation of an international database to collect uniformly clinical and pathologic information with the ultimate goal of fostering collaboration and to facilitate the identification of surrogate endpoints of long-term survival.”

Dr. Travis is a nonpaid pathology consultant for the LCMC3 and LCMC4 trials.

Adjuvant pembrolizumab significantly improves disease-free survival (DFS) compared to placebo in patients with early-stage non–small cell lung cancer (NSCLC) who have undergone complete resection, according to findings from the phase 3 PEARLS/KEYNOTE-091 (PEARLS) study.

Patients in the pembrolizumab arm demonstrated median DFS nearly 12 months longer than those in the placebo arm (53.6 vs. 42.0 months). Investigators observed a DFS benefit for patients with any programmed death-ligand 1 (PD-L1) expression.

“We believe that pembrolizumab has the potential to become a new adjuvant treatment option for patient with [stage IB to IIIA] non–small cell lung cancer following complete resection and adjuvant chemotherapy when recommended,” concluded first author Luis Paz-Ares, MD, chair of the clinical research unit at Hospital Universitario 12 de Octubre, CNIO & Universidad Complutense, Madrid. “Pembrolizumab provided a benefit regardless of pathological stage and PD-L1 progression subgroup.”

The findings were presented by Dr. Paz-Ares at the European Society for Medical Oncology (ESMO) March virtual plenary session and published March 17 in Annals of Oncology.

Pembrolizumab is the standard treatment for patients with advanced NSCLC, but its efficacy in early-stage disease remains unclear. To determine whether patients with early-stage disease benefit from pembrolizumab, Dr. Paz-Ares and colleagues randomized 1,177 adults with stage IB, II, or IIIA NSCLC to 200 mg of pembrolizumab (n = 590) or placebo (n = 587) every 3 weeks.

All patients had Eastern Cooperative Oncology Group performance status of 0-1, and any level of PD-L1 expression. Of the study participants, 168 in the pembrolizumab arm and 165 in the placebo arm had PD-L1 expression and a tumor proportion score (TPS) of at least 50%.

Overall, patients receiving pembrolizumab had a DFS of 53.6 months compared to 42.0 months in the placebo arm (hazard ratio [HR], 0.76; P = .0014). The DFS benefit was generally consistent across patients with PD-L1 TPS <1%, 1%-49%, and ≥50%. In the subset of patients with PD-L1 TPS ≥50%, a slightly higher percentage of patients in the pembrolizumab group demonstrated DFS at 18 months (71.7% vs. 70.2%), but the difference did not reach statistical significance (HR, 0.82; P = .14).

Overall survival (OS) at 18 months was 91.7% in the treatment arm and 91.3% in the placebo arm (HR, 0.87; P = .17), but the data were immature.

“The disease-free survival benefit was observed across most prespecified subgroups,” Dr. Paz-Ares said.

No new safety concerns were raised. Grade 3 or greater adverse events occurred in 34.1% of patients in the treatment arm and 25.8% in the placebo arm. Adverse events led to discontinuation in 19.8% of patients receiving pembrolizumab and 5.9% of patients in the placebo group.

Invited discussant Martin Reck, MD, said these findings represent forward progress. “We do see many patients with distant relapse, which indicates that we have to improve our control of the systemic relapse,” said Dr. Reck, head of the department of thoracic oncology and the clinical trial department at the Lungen Clinic Grosshansdorf, Germany.

Prior data provide a rationale for using immune checkpoint inhibition in early-stage NSCLC, and both the PEARLS study and the IMpower010 trial evaluating atezolizumab in a similar setting have demonstrated relevant improvements in DFS.

“I think we are entering the times of perioperative immunotherapies. We are seeing the first signals of efficacy for adjuvant immunotherapy in two large, randomized trials,” Dr. Reck said.

Based on the PEARLS trial results, Dr. Reck said that PD-L1 appears to have predictive and prognostic value but noted that “several other clinical trials say PD-L1 expression is a poor prognostic marker” for sensitivity to immune checkpoint inhibitor. Given this potential inconsistency, Dr. Reck called for further follow-up in this patient population and for studies in larger groups of patients to further delineate the role of PD-L1 as well as EGFR mutations and adjuvant chemotherapy in patients with early NSCLC.

The PEARLS study was funded by Merck Sharp & Dohme Corp. Dr. Paz-Ares and Dr. Reck disclosed numerous relationships with pharmaceutical companies.

Adjuvant pembrolizumab significantly improves disease-free survival (DFS) compared to placebo in patients with early-stage non–small cell lung cancer (NSCLC) who have undergone complete resection, according to findings from the phase 3 PEARLS/KEYNOTE-091 (PEARLS) study.

Patients in the pembrolizumab arm demonstrated median DFS nearly 12 months longer than those in the placebo arm (53.6 vs. 42.0 months). Investigators observed a DFS benefit for patients with any programmed death-ligand 1 (PD-L1) expression.

“We believe that pembrolizumab has the potential to become a new adjuvant treatment option for patient with [stage IB to IIIA] non–small cell lung cancer following complete resection and adjuvant chemotherapy when recommended,” concluded first author Luis Paz-Ares, MD, chair of the clinical research unit at Hospital Universitario 12 de Octubre, CNIO & Universidad Complutense, Madrid. “Pembrolizumab provided a benefit regardless of pathological stage and PD-L1 progression subgroup.”

The findings were presented by Dr. Paz-Ares at the European Society for Medical Oncology (ESMO) March virtual plenary session and published March 17 in Annals of Oncology.

Pembrolizumab is the standard treatment for patients with advanced NSCLC, but its efficacy in early-stage disease remains unclear. To determine whether patients with early-stage disease benefit from pembrolizumab, Dr. Paz-Ares and colleagues randomized 1,177 adults with stage IB, II, or IIIA NSCLC to 200 mg of pembrolizumab (n = 590) or placebo (n = 587) every 3 weeks.

All patients had Eastern Cooperative Oncology Group performance status of 0-1, and any level of PD-L1 expression. Of the study participants, 168 in the pembrolizumab arm and 165 in the placebo arm had PD-L1 expression and a tumor proportion score (TPS) of at least 50%.

Overall, patients receiving pembrolizumab had a DFS of 53.6 months compared to 42.0 months in the placebo arm (hazard ratio [HR], 0.76; P = .0014). The DFS benefit was generally consistent across patients with PD-L1 TPS <1%, 1%-49%, and ≥50%. In the subset of patients with PD-L1 TPS ≥50%, a slightly higher percentage of patients in the pembrolizumab group demonstrated DFS at 18 months (71.7% vs. 70.2%), but the difference did not reach statistical significance (HR, 0.82; P = .14).

Overall survival (OS) at 18 months was 91.7% in the treatment arm and 91.3% in the placebo arm (HR, 0.87; P = .17), but the data were immature.

“The disease-free survival benefit was observed across most prespecified subgroups,” Dr. Paz-Ares said.

No new safety concerns were raised. Grade 3 or greater adverse events occurred in 34.1% of patients in the treatment arm and 25.8% in the placebo arm. Adverse events led to discontinuation in 19.8% of patients receiving pembrolizumab and 5.9% of patients in the placebo group.

Invited discussant Martin Reck, MD, said these findings represent forward progress. “We do see many patients with distant relapse, which indicates that we have to improve our control of the systemic relapse,” said Dr. Reck, head of the department of thoracic oncology and the clinical trial department at the Lungen Clinic Grosshansdorf, Germany.

Prior data provide a rationale for using immune checkpoint inhibition in early-stage NSCLC, and both the PEARLS study and the IMpower010 trial evaluating atezolizumab in a similar setting have demonstrated relevant improvements in DFS.

“I think we are entering the times of perioperative immunotherapies. We are seeing the first signals of efficacy for adjuvant immunotherapy in two large, randomized trials,” Dr. Reck said.

Based on the PEARLS trial results, Dr. Reck said that PD-L1 appears to have predictive and prognostic value but noted that “several other clinical trials say PD-L1 expression is a poor prognostic marker” for sensitivity to immune checkpoint inhibitor. Given this potential inconsistency, Dr. Reck called for further follow-up in this patient population and for studies in larger groups of patients to further delineate the role of PD-L1 as well as EGFR mutations and adjuvant chemotherapy in patients with early NSCLC.

The PEARLS study was funded by Merck Sharp & Dohme Corp. Dr. Paz-Ares and Dr. Reck disclosed numerous relationships with pharmaceutical companies.

Adjuvant pembrolizumab significantly improves disease-free survival (DFS) compared to placebo in patients with early-stage non–small cell lung cancer (NSCLC) who have undergone complete resection, according to findings from the phase 3 PEARLS/KEYNOTE-091 (PEARLS) study.

Patients in the pembrolizumab arm demonstrated median DFS nearly 12 months longer than those in the placebo arm (53.6 vs. 42.0 months). Investigators observed a DFS benefit for patients with any programmed death-ligand 1 (PD-L1) expression.

“We believe that pembrolizumab has the potential to become a new adjuvant treatment option for patient with [stage IB to IIIA] non–small cell lung cancer following complete resection and adjuvant chemotherapy when recommended,” concluded first author Luis Paz-Ares, MD, chair of the clinical research unit at Hospital Universitario 12 de Octubre, CNIO & Universidad Complutense, Madrid. “Pembrolizumab provided a benefit regardless of pathological stage and PD-L1 progression subgroup.”

The findings were presented by Dr. Paz-Ares at the European Society for Medical Oncology (ESMO) March virtual plenary session and published March 17 in Annals of Oncology.

Pembrolizumab is the standard treatment for patients with advanced NSCLC, but its efficacy in early-stage disease remains unclear. To determine whether patients with early-stage disease benefit from pembrolizumab, Dr. Paz-Ares and colleagues randomized 1,177 adults with stage IB, II, or IIIA NSCLC to 200 mg of pembrolizumab (n = 590) or placebo (n = 587) every 3 weeks.

All patients had Eastern Cooperative Oncology Group performance status of 0-1, and any level of PD-L1 expression. Of the study participants, 168 in the pembrolizumab arm and 165 in the placebo arm had PD-L1 expression and a tumor proportion score (TPS) of at least 50%.

Overall, patients receiving pembrolizumab had a DFS of 53.6 months compared to 42.0 months in the placebo arm (hazard ratio [HR], 0.76; P = .0014). The DFS benefit was generally consistent across patients with PD-L1 TPS <1%, 1%-49%, and ≥50%. In the subset of patients with PD-L1 TPS ≥50%, a slightly higher percentage of patients in the pembrolizumab group demonstrated DFS at 18 months (71.7% vs. 70.2%), but the difference did not reach statistical significance (HR, 0.82; P = .14).

Overall survival (OS) at 18 months was 91.7% in the treatment arm and 91.3% in the placebo arm (HR, 0.87; P = .17), but the data were immature.

“The disease-free survival benefit was observed across most prespecified subgroups,” Dr. Paz-Ares said.

No new safety concerns were raised. Grade 3 or greater adverse events occurred in 34.1% of patients in the treatment arm and 25.8% in the placebo arm. Adverse events led to discontinuation in 19.8% of patients receiving pembrolizumab and 5.9% of patients in the placebo group.

Invited discussant Martin Reck, MD, said these findings represent forward progress. “We do see many patients with distant relapse, which indicates that we have to improve our control of the systemic relapse,” said Dr. Reck, head of the department of thoracic oncology and the clinical trial department at the Lungen Clinic Grosshansdorf, Germany.

Prior data provide a rationale for using immune checkpoint inhibition in early-stage NSCLC, and both the PEARLS study and the IMpower010 trial evaluating atezolizumab in a similar setting have demonstrated relevant improvements in DFS.

“I think we are entering the times of perioperative immunotherapies. We are seeing the first signals of efficacy for adjuvant immunotherapy in two large, randomized trials,” Dr. Reck said.

Based on the PEARLS trial results, Dr. Reck said that PD-L1 appears to have predictive and prognostic value but noted that “several other clinical trials say PD-L1 expression is a poor prognostic marker” for sensitivity to immune checkpoint inhibitor. Given this potential inconsistency, Dr. Reck called for further follow-up in this patient population and for studies in larger groups of patients to further delineate the role of PD-L1 as well as EGFR mutations and adjuvant chemotherapy in patients with early NSCLC.

The PEARLS study was funded by Merck Sharp & Dohme Corp. Dr. Paz-Ares and Dr. Reck disclosed numerous relationships with pharmaceutical companies.

Just about every patient-reported outcome favors adding immunotherapy to standard chemotherapy for patients with metastatic non-small cell lung cancer, according to an analysis presented at the annual European Lung Cancer Congress (ELCC) on March 30.

“Overall, it is very clear that chemotherapy plus immunotherapy prolongs the time to symptom deterioration and actually improves symptoms” in this patient population, said study discussant Luis Paz-Ares, MD, PhD, chair of medical oncology at the Hospital Universitario 12 de Octubre, Madrid, who was not involved in the research.

Last September, investigators reported efficacy outcomes from the phase 3 POSEIDON trial, which randomized 1,013 patients with EGFR/ALK wild-type mNSCLC to one of three first-line options: chemotherapy alone, chemotherapy plus the checkpoint inhibitor durvalumab, or chemotherapy plus two check-point inhibitors, durvalumab and tremelimumab. The analysis showed improved progression-free survival in both immunotherapy arms as well as a significant 2.3-month overall survival advantage with dual immunotherapy and a nonsignificant 1.6-month advantage with single agent durvalumab.

At the ELCC meeting, study presenter and lead investigator Edward Garon, MD, reported the latest data on the trial’s secondary endpoints: patient-reported outcomes. Global health status, functioning, and symptom scores were assessed using two questionnaires, the EORTC QLQ-C30 and EORTC QLQ-LC13.

Overall, Dr. Garon and colleagues reported a longer time to deterioration in all three areas – global health status, functioning, and symptoms – for patients who received immunotherapy versus chemotherapy alone, with similar results in both immunotherapy arms.

Time to deterioration in global health status, for instance, was a median of about 8 months on both immunotherapy regimens versus 5.6 months with chemotherapy alone. The positive findings held for many patient-reported treatment side effects, including dyspnea, hemoptysis, nausea/vomiting, and insomnia, but the benefits of adding immunotherapy weren’t always statistically significant.

Adding one or both checkpoint inhibitors to chemotherapy “improved efficacy while delaying deterioration in symptoms, functioning, and [health-related quality of life] versus chemotherapy alone in patients with mNSCLC,” concluded Dr. Garon, a thoracic medical oncologist at the University of California, Los Angeles. Plus, he added, “the pattern was observed across nearly all prespecified symptoms and domains of interest.”

According to study discussant Dr. Paz-Ares, “the data seem to be very consistent with all the trials asking similar questions.” The important thing here is figuring out the ideal candidates for dual inhibitor therapy, he said.

With positive efficacy and patient-reported outcomes for single and dual immunotherapy in this trial, it’s a “relatively straightforward” decision to add immunotherapy to chemotherapy for patients with mNSCLC, Massimo Di Maio, a medical oncologist at the University of Turin, Italy, said in an editorial on the ELCC’s news site.

However, that’s not always the case for every cancer type, which makes patient-reported outcomes “crucial” for determining the right treatment for each patient. Some might opt for a modest survival benefit regardless of the side effects, while others might favor a less toxic approach, even it means not living quite as long, he said.

The problem, he stressed, is that trials often release efficacy data well before patient-reported outcomes, which makes weighing the benefits and risks of a treat-ment option more difficult. The delay between efficacy and patient-reported outcome data was about 6 months in the POSEIDON trial.

“Timing is key when it comes to using [patient reported outcomes] for decision-making in oncology,” Dr. Di Maio said. “In fact, to enable a full assessment of a treatment, results should be published concurrently with the efficacy and safety data. Unfortunately, this is generally not the case.”

POSEIDON was funded by AstraZeneca, which markets durvalumab and is developing tremelimumab. Dr. Garon reported grants from the company. Dr. Paz-Ares reported honoraria and institutional research grants from AstraZeneca. Dr. Di Maio is a consultant for AstraZeneca and reported receiving honoraria and personal fees from the company.

Just about every patient-reported outcome favors adding immunotherapy to standard chemotherapy for patients with metastatic non-small cell lung cancer, according to an analysis presented at the annual European Lung Cancer Congress (ELCC) on March 30.

“Overall, it is very clear that chemotherapy plus immunotherapy prolongs the time to symptom deterioration and actually improves symptoms” in this patient population, said study discussant Luis Paz-Ares, MD, PhD, chair of medical oncology at the Hospital Universitario 12 de Octubre, Madrid, who was not involved in the research.

Last September, investigators reported efficacy outcomes from the phase 3 POSEIDON trial, which randomized 1,013 patients with EGFR/ALK wild-type mNSCLC to one of three first-line options: chemotherapy alone, chemotherapy plus the checkpoint inhibitor durvalumab, or chemotherapy plus two check-point inhibitors, durvalumab and tremelimumab. The analysis showed improved progression-free survival in both immunotherapy arms as well as a significant 2.3-month overall survival advantage with dual immunotherapy and a nonsignificant 1.6-month advantage with single agent durvalumab.

At the ELCC meeting, study presenter and lead investigator Edward Garon, MD, reported the latest data on the trial’s secondary endpoints: patient-reported outcomes. Global health status, functioning, and symptom scores were assessed using two questionnaires, the EORTC QLQ-C30 and EORTC QLQ-LC13.

Overall, Dr. Garon and colleagues reported a longer time to deterioration in all three areas – global health status, functioning, and symptoms – for patients who received immunotherapy versus chemotherapy alone, with similar results in both immunotherapy arms.

Time to deterioration in global health status, for instance, was a median of about 8 months on both immunotherapy regimens versus 5.6 months with chemotherapy alone. The positive findings held for many patient-reported treatment side effects, including dyspnea, hemoptysis, nausea/vomiting, and insomnia, but the benefits of adding immunotherapy weren’t always statistically significant.

Adding one or both checkpoint inhibitors to chemotherapy “improved efficacy while delaying deterioration in symptoms, functioning, and [health-related quality of life] versus chemotherapy alone in patients with mNSCLC,” concluded Dr. Garon, a thoracic medical oncologist at the University of California, Los Angeles. Plus, he added, “the pattern was observed across nearly all prespecified symptoms and domains of interest.”

According to study discussant Dr. Paz-Ares, “the data seem to be very consistent with all the trials asking similar questions.” The important thing here is figuring out the ideal candidates for dual inhibitor therapy, he said.

With positive efficacy and patient-reported outcomes for single and dual immunotherapy in this trial, it’s a “relatively straightforward” decision to add immunotherapy to chemotherapy for patients with mNSCLC, Massimo Di Maio, a medical oncologist at the University of Turin, Italy, said in an editorial on the ELCC’s news site.

However, that’s not always the case for every cancer type, which makes patient-reported outcomes “crucial” for determining the right treatment for each patient. Some might opt for a modest survival benefit regardless of the side effects, while others might favor a less toxic approach, even it means not living quite as long, he said.

The problem, he stressed, is that trials often release efficacy data well before patient-reported outcomes, which makes weighing the benefits and risks of a treat-ment option more difficult. The delay between efficacy and patient-reported outcome data was about 6 months in the POSEIDON trial.

“Timing is key when it comes to using [patient reported outcomes] for decision-making in oncology,” Dr. Di Maio said. “In fact, to enable a full assessment of a treatment, results should be published concurrently with the efficacy and safety data. Unfortunately, this is generally not the case.”

POSEIDON was funded by AstraZeneca, which markets durvalumab and is developing tremelimumab. Dr. Garon reported grants from the company. Dr. Paz-Ares reported honoraria and institutional research grants from AstraZeneca. Dr. Di Maio is a consultant for AstraZeneca and reported receiving honoraria and personal fees from the company.

Just about every patient-reported outcome favors adding immunotherapy to standard chemotherapy for patients with metastatic non-small cell lung cancer, according to an analysis presented at the annual European Lung Cancer Congress (ELCC) on March 30.

“Overall, it is very clear that chemotherapy plus immunotherapy prolongs the time to symptom deterioration and actually improves symptoms” in this patient population, said study discussant Luis Paz-Ares, MD, PhD, chair of medical oncology at the Hospital Universitario 12 de Octubre, Madrid, who was not involved in the research.

Last September, investigators reported efficacy outcomes from the phase 3 POSEIDON trial, which randomized 1,013 patients with EGFR/ALK wild-type mNSCLC to one of three first-line options: chemotherapy alone, chemotherapy plus the checkpoint inhibitor durvalumab, or chemotherapy plus two check-point inhibitors, durvalumab and tremelimumab. The analysis showed improved progression-free survival in both immunotherapy arms as well as a significant 2.3-month overall survival advantage with dual immunotherapy and a nonsignificant 1.6-month advantage with single agent durvalumab.

At the ELCC meeting, study presenter and lead investigator Edward Garon, MD, reported the latest data on the trial’s secondary endpoints: patient-reported outcomes. Global health status, functioning, and symptom scores were assessed using two questionnaires, the EORTC QLQ-C30 and EORTC QLQ-LC13.

Overall, Dr. Garon and colleagues reported a longer time to deterioration in all three areas – global health status, functioning, and symptoms – for patients who received immunotherapy versus chemotherapy alone, with similar results in both immunotherapy arms.

Time to deterioration in global health status, for instance, was a median of about 8 months on both immunotherapy regimens versus 5.6 months with chemotherapy alone. The positive findings held for many patient-reported treatment side effects, including dyspnea, hemoptysis, nausea/vomiting, and insomnia, but the benefits of adding immunotherapy weren’t always statistically significant.

Adding one or both checkpoint inhibitors to chemotherapy “improved efficacy while delaying deterioration in symptoms, functioning, and [health-related quality of life] versus chemotherapy alone in patients with mNSCLC,” concluded Dr. Garon, a thoracic medical oncologist at the University of California, Los Angeles. Plus, he added, “the pattern was observed across nearly all prespecified symptoms and domains of interest.”

According to study discussant Dr. Paz-Ares, “the data seem to be very consistent with all the trials asking similar questions.” The important thing here is figuring out the ideal candidates for dual inhibitor therapy, he said.

With positive efficacy and patient-reported outcomes for single and dual immunotherapy in this trial, it’s a “relatively straightforward” decision to add immunotherapy to chemotherapy for patients with mNSCLC, Massimo Di Maio, a medical oncologist at the University of Turin, Italy, said in an editorial on the ELCC’s news site.

However, that’s not always the case for every cancer type, which makes patient-reported outcomes “crucial” for determining the right treatment for each patient. Some might opt for a modest survival benefit regardless of the side effects, while others might favor a less toxic approach, even it means not living quite as long, he said.

The problem, he stressed, is that trials often release efficacy data well before patient-reported outcomes, which makes weighing the benefits and risks of a treat-ment option more difficult. The delay between efficacy and patient-reported outcome data was about 6 months in the POSEIDON trial.

“Timing is key when it comes to using [patient reported outcomes] for decision-making in oncology,” Dr. Di Maio said. “In fact, to enable a full assessment of a treatment, results should be published concurrently with the efficacy and safety data. Unfortunately, this is generally not the case.”

POSEIDON was funded by AstraZeneca, which markets durvalumab and is developing tremelimumab. Dr. Garon reported grants from the company. Dr. Paz-Ares reported honoraria and institutional research grants from AstraZeneca. Dr. Di Maio is a consultant for AstraZeneca and reported receiving honoraria and personal fees from the company.

The link between obesity and cancer has increasingly been emphasized in public health messages, but is the current message correct?

“Being overweight or having obesity increases your risk of getting cancer,” warns the U.S. Centers for Disease Control and Prevention. It warns that overweight/obesity is “linked with a higher risk of getting 13 types of cancer ... [which] make up 40% of all cancers diagnosed in the United States each year.”

But that message, which is also promulgated by many cancer organizations, is based on data from observational studies, which have many limitations.

A new study based on Mendelian randomization studies has come to a slightly different conclusion and has found a potential causal association with just six cancers.

In addition, it found an inverse relationship for breast cancer, in which early-life obesity was associated with a reduced risk of breast cancer, and the relationship with obesity was “complicated” for lung and prostate cancer.

The study, headed by Zhe Fang, MBBS, Harvard T. H. Chan School of Public Health, Boston, Mass., was published in the Journal of the National Cancer Institute

“For a seemingly straightforward question of whether excessive body fatness causes cancer, the answer may not be straightforward after all,” writes Song Yao, PhD, professor of oncology, Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., in an accompanying editorial

“How to craft a simple public health message to convey the complexity and nuances of the relationships may be a challenge to be grappled with going forward,” he added.

In an interview, Dr. Yao said that it “really depends on what kind of message you want to get out.”

“If you want to talk about cancer overall, as one disease, we all know that a clear association with obesity does not exist,” he said. “It’s not that simple.”

“You really cannot say that obesity increases cancer risk overall,” he said.

For some cancers included in the study, Dr. Yao continued, it was “very clear that obesity increased the risk ... but for some other cancer types, we either don’t have enough data yet or the association is not as consistent.”

This, he said, is especially the case for prostate and lung cancer.

All of this indicates that there is a complex relationship between obesity and cancer risk, he maintains.

“We always think obesity is bad, not only for cancer but also for more common conditions, like hypertension, diabetes, and cardiovascular disease,” Dr. Yao noted. This points to the link between obesity and chronic inflammation, he added.

However, there are also other hypotheses, including synthesis of estrogen in adipose tissue, which may explain the link between obesity and breast cancer risk in older women.

However, in younger women, obesity protects against breast cancer, and “we really don’t know why,” Dr. Yao said.

The new study used Mendelian randomization to examine these relationships. This is a “new tool that we have developed over the past 20 years or so, largely because there is so much data coming from genome-wide association studies,” Dr. Yao explained.

It has “advantages” over other methods, including observational studies. One of its strengths is that it is “not impacted by reverse causality,” because genetic risk does not change over time.

However, he said, it is “quite straightforward to think that the genetics do not change, but at the same time, the environment we live in throughout our life course changes,” and the impact of genetic variants may be “washed out.”

How genetics influences cancer risk may therefore change over time, and it is a “dynamic process,” Dr. Yao commented.

In addition, this approach has its own limitations, he said, because it depends on how much of the variation in a given measure can be attributed to genetic factors.
 

New conclusions

In their study, Dr. Fang and colleagues reviewed 204 meta-analyses of 2,179 individual estimates from 507 cohort or case-control studies. They found “strong evidence” that supports the association between obesity and 11 cancers.

These are esophageal adenocarcinoma, multiple myeloma, and cancers of the gastric cardia, colon, rectum, biliary tract system, pancreas, breast, endometrium, ovary, and kidney.

They note, however, that the associations “may be causal for some malignancies” but that the co-occurrence of obesity with various cancer risk factors means that others may be “susceptible to potential confounding bias.”

To overcome some of these limitations, the team looked to Mendelian randomization studies that examined the association between genetic variants linked to body mass index (BMI), indicating lifetime risk of high BMI, and cancer risk for a range of cancer types.

These Mendelian randomization studies were then compared with the results of large-scale conventional observational studies, as well as with evidence in reports from the International Agency for Research on Cancer and the World Cancer Research Fund–American Institute of Cancer Research, which also include experimental studies.

The researchers say that, overall, the Mendelian randomization studies “further establish the causality of obesity” with six cancer types: colorectal, endometrial, ovarian, kidney, and pancreatic cancer, and esophageal adenocarcinoma.

In addition, these studies further establish the inverse relationship of early-life obesity with breast cancer.

However, the approach could not confirm a positive association between obesity and gallbladder and gastric cardia cancer, as well as multiple myeloma.

“This could be due to low power,” the team suggests, “and larger studies are required.”

With respect to lung cancer, the Mendelian randomization identified a positive association with obesity that supports the inverse association identified in observational studies, that is, that obesity may reduce the risk for lung cancer.

The researchers suggest this may reflect reverse causality related to the loss of lean body mass before diagnosis, as well as confounding by smoking.

For prostate cancer, the evidence was “conflicting” and “implies a complicated role of obesity,” Dr. Zhang and colleagues comment.

The link between obesity and lower prostate-specific antigen levels, they suggest, may result in a detection bias by masking the presence of prostate cancer, or it “could be biological” in origin, owing to reduced androgen levels.

For six cancer types for which a causal relationship with obesity could be established, the effect estimates from the Mendelian randomization studies were stronger than those seen in conventional studies, with the magnitude of risk ranging from 1.14-fold for early-life obesity and breast cancer to 1.37-fold for adult obesity and esophageal adenocarcinoma.

In another editorial accompanying the new study, Graham A. Colditz, MD, DrPH, from Washington University School of Medicine, St. Louis, underlined that childhood and adolescent obesity and their contribution to cancer risk need further attention.

“To reap the reward from past research, we must act to implement effective strategies to reduce childhood and adolescent adiposity, reduce excess weight gain in adult years, and maintain a healthy weight,” he writes.

“This will require us to change the way we live, but COVID-19 has shown we can make changes to how we live and work. Let us keep the changes we have already made, or take on new ones, that will cut our collective cancer toll,” he implores.

No funding for the study was described. Dr. Colditz is supported by the Breast Cancer Research Foundation. No other relevant financial relationships were described.

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

The link between obesity and cancer has increasingly been emphasized in public health messages, but is the current message correct?

“Being overweight or having obesity increases your risk of getting cancer,” warns the U.S. Centers for Disease Control and Prevention. It warns that overweight/obesity is “linked with a higher risk of getting 13 types of cancer ... [which] make up 40% of all cancers diagnosed in the United States each year.”

But that message, which is also promulgated by many cancer organizations, is based on data from observational studies, which have many limitations.

A new study based on Mendelian randomization studies has come to a slightly different conclusion and has found a potential causal association with just six cancers.

In addition, it found an inverse relationship for breast cancer, in which early-life obesity was associated with a reduced risk of breast cancer, and the relationship with obesity was “complicated” for lung and prostate cancer.

The study, headed by Zhe Fang, MBBS, Harvard T. H. Chan School of Public Health, Boston, Mass., was published in the Journal of the National Cancer Institute

“For a seemingly straightforward question of whether excessive body fatness causes cancer, the answer may not be straightforward after all,” writes Song Yao, PhD, professor of oncology, Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., in an accompanying editorial

“How to craft a simple public health message to convey the complexity and nuances of the relationships may be a challenge to be grappled with going forward,” he added.

In an interview, Dr. Yao said that it “really depends on what kind of message you want to get out.”

“If you want to talk about cancer overall, as one disease, we all know that a clear association with obesity does not exist,” he said. “It’s not that simple.”

“You really cannot say that obesity increases cancer risk overall,” he said.

For some cancers included in the study, Dr. Yao continued, it was “very clear that obesity increased the risk ... but for some other cancer types, we either don’t have enough data yet or the association is not as consistent.”

This, he said, is especially the case for prostate and lung cancer.

All of this indicates that there is a complex relationship between obesity and cancer risk, he maintains.

“We always think obesity is bad, not only for cancer but also for more common conditions, like hypertension, diabetes, and cardiovascular disease,” Dr. Yao noted. This points to the link between obesity and chronic inflammation, he added.

However, there are also other hypotheses, including synthesis of estrogen in adipose tissue, which may explain the link between obesity and breast cancer risk in older women.

However, in younger women, obesity protects against breast cancer, and “we really don’t know why,” Dr. Yao said.

The new study used Mendelian randomization to examine these relationships. This is a “new tool that we have developed over the past 20 years or so, largely because there is so much data coming from genome-wide association studies,” Dr. Yao explained.

It has “advantages” over other methods, including observational studies. One of its strengths is that it is “not impacted by reverse causality,” because genetic risk does not change over time.

However, he said, it is “quite straightforward to think that the genetics do not change, but at the same time, the environment we live in throughout our life course changes,” and the impact of genetic variants may be “washed out.”

How genetics influences cancer risk may therefore change over time, and it is a “dynamic process,” Dr. Yao commented.

In addition, this approach has its own limitations, he said, because it depends on how much of the variation in a given measure can be attributed to genetic factors.
 

New conclusions

In their study, Dr. Fang and colleagues reviewed 204 meta-analyses of 2,179 individual estimates from 507 cohort or case-control studies. They found “strong evidence” that supports the association between obesity and 11 cancers.

These are esophageal adenocarcinoma, multiple myeloma, and cancers of the gastric cardia, colon, rectum, biliary tract system, pancreas, breast, endometrium, ovary, and kidney.

They note, however, that the associations “may be causal for some malignancies” but that the co-occurrence of obesity with various cancer risk factors means that others may be “susceptible to potential confounding bias.”

To overcome some of these limitations, the team looked to Mendelian randomization studies that examined the association between genetic variants linked to body mass index (BMI), indicating lifetime risk of high BMI, and cancer risk for a range of cancer types.

These Mendelian randomization studies were then compared with the results of large-scale conventional observational studies, as well as with evidence in reports from the International Agency for Research on Cancer and the World Cancer Research Fund–American Institute of Cancer Research, which also include experimental studies.

The researchers say that, overall, the Mendelian randomization studies “further establish the causality of obesity” with six cancer types: colorectal, endometrial, ovarian, kidney, and pancreatic cancer, and esophageal adenocarcinoma.

In addition, these studies further establish the inverse relationship of early-life obesity with breast cancer.

However, the approach could not confirm a positive association between obesity and gallbladder and gastric cardia cancer, as well as multiple myeloma.

“This could be due to low power,” the team suggests, “and larger studies are required.”

With respect to lung cancer, the Mendelian randomization identified a positive association with obesity that supports the inverse association identified in observational studies, that is, that obesity may reduce the risk for lung cancer.

The researchers suggest this may reflect reverse causality related to the loss of lean body mass before diagnosis, as well as confounding by smoking.

For prostate cancer, the evidence was “conflicting” and “implies a complicated role of obesity,” Dr. Zhang and colleagues comment.

The link between obesity and lower prostate-specific antigen levels, they suggest, may result in a detection bias by masking the presence of prostate cancer, or it “could be biological” in origin, owing to reduced androgen levels.

For six cancer types for which a causal relationship with obesity could be established, the effect estimates from the Mendelian randomization studies were stronger than those seen in conventional studies, with the magnitude of risk ranging from 1.14-fold for early-life obesity and breast cancer to 1.37-fold for adult obesity and esophageal adenocarcinoma.

In another editorial accompanying the new study, Graham A. Colditz, MD, DrPH, from Washington University School of Medicine, St. Louis, underlined that childhood and adolescent obesity and their contribution to cancer risk need further attention.

“To reap the reward from past research, we must act to implement effective strategies to reduce childhood and adolescent adiposity, reduce excess weight gain in adult years, and maintain a healthy weight,” he writes.

“This will require us to change the way we live, but COVID-19 has shown we can make changes to how we live and work. Let us keep the changes we have already made, or take on new ones, that will cut our collective cancer toll,” he implores.

No funding for the study was described. Dr. Colditz is supported by the Breast Cancer Research Foundation. No other relevant financial relationships were described.

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

The link between obesity and cancer has increasingly been emphasized in public health messages, but is the current message correct?

“Being overweight or having obesity increases your risk of getting cancer,” warns the U.S. Centers for Disease Control and Prevention. It warns that overweight/obesity is “linked with a higher risk of getting 13 types of cancer ... [which] make up 40% of all cancers diagnosed in the United States each year.”

But that message, which is also promulgated by many cancer organizations, is based on data from observational studies, which have many limitations.

A new study based on Mendelian randomization studies has come to a slightly different conclusion and has found a potential causal association with just six cancers.

In addition, it found an inverse relationship for breast cancer, in which early-life obesity was associated with a reduced risk of breast cancer, and the relationship with obesity was “complicated” for lung and prostate cancer.

The study, headed by Zhe Fang, MBBS, Harvard T. H. Chan School of Public Health, Boston, Mass., was published in the Journal of the National Cancer Institute

“For a seemingly straightforward question of whether excessive body fatness causes cancer, the answer may not be straightforward after all,” writes Song Yao, PhD, professor of oncology, Roswell Park Comprehensive Cancer Center, Buffalo, N.Y., in an accompanying editorial

“How to craft a simple public health message to convey the complexity and nuances of the relationships may be a challenge to be grappled with going forward,” he added.

In an interview, Dr. Yao said that it “really depends on what kind of message you want to get out.”

“If you want to talk about cancer overall, as one disease, we all know that a clear association with obesity does not exist,” he said. “It’s not that simple.”

“You really cannot say that obesity increases cancer risk overall,” he said.

For some cancers included in the study, Dr. Yao continued, it was “very clear that obesity increased the risk ... but for some other cancer types, we either don’t have enough data yet or the association is not as consistent.”

This, he said, is especially the case for prostate and lung cancer.

All of this indicates that there is a complex relationship between obesity and cancer risk, he maintains.

“We always think obesity is bad, not only for cancer but also for more common conditions, like hypertension, diabetes, and cardiovascular disease,” Dr. Yao noted. This points to the link between obesity and chronic inflammation, he added.

However, there are also other hypotheses, including synthesis of estrogen in adipose tissue, which may explain the link between obesity and breast cancer risk in older women.

However, in younger women, obesity protects against breast cancer, and “we really don’t know why,” Dr. Yao said.

The new study used Mendelian randomization to examine these relationships. This is a “new tool that we have developed over the past 20 years or so, largely because there is so much data coming from genome-wide association studies,” Dr. Yao explained.

It has “advantages” over other methods, including observational studies. One of its strengths is that it is “not impacted by reverse causality,” because genetic risk does not change over time.

However, he said, it is “quite straightforward to think that the genetics do not change, but at the same time, the environment we live in throughout our life course changes,” and the impact of genetic variants may be “washed out.”

How genetics influences cancer risk may therefore change over time, and it is a “dynamic process,” Dr. Yao commented.

In addition, this approach has its own limitations, he said, because it depends on how much of the variation in a given measure can be attributed to genetic factors.
 

New conclusions

In their study, Dr. Fang and colleagues reviewed 204 meta-analyses of 2,179 individual estimates from 507 cohort or case-control studies. They found “strong evidence” that supports the association between obesity and 11 cancers.

These are esophageal adenocarcinoma, multiple myeloma, and cancers of the gastric cardia, colon, rectum, biliary tract system, pancreas, breast, endometrium, ovary, and kidney.

They note, however, that the associations “may be causal for some malignancies” but that the co-occurrence of obesity with various cancer risk factors means that others may be “susceptible to potential confounding bias.”

To overcome some of these limitations, the team looked to Mendelian randomization studies that examined the association between genetic variants linked to body mass index (BMI), indicating lifetime risk of high BMI, and cancer risk for a range of cancer types.

These Mendelian randomization studies were then compared with the results of large-scale conventional observational studies, as well as with evidence in reports from the International Agency for Research on Cancer and the World Cancer Research Fund–American Institute of Cancer Research, which also include experimental studies.

The researchers say that, overall, the Mendelian randomization studies “further establish the causality of obesity” with six cancer types: colorectal, endometrial, ovarian, kidney, and pancreatic cancer, and esophageal adenocarcinoma.

In addition, these studies further establish the inverse relationship of early-life obesity with breast cancer.

However, the approach could not confirm a positive association between obesity and gallbladder and gastric cardia cancer, as well as multiple myeloma.

“This could be due to low power,” the team suggests, “and larger studies are required.”

With respect to lung cancer, the Mendelian randomization identified a positive association with obesity that supports the inverse association identified in observational studies, that is, that obesity may reduce the risk for lung cancer.

The researchers suggest this may reflect reverse causality related to the loss of lean body mass before diagnosis, as well as confounding by smoking.

For prostate cancer, the evidence was “conflicting” and “implies a complicated role of obesity,” Dr. Zhang and colleagues comment.

The link between obesity and lower prostate-specific antigen levels, they suggest, may result in a detection bias by masking the presence of prostate cancer, or it “could be biological” in origin, owing to reduced androgen levels.

For six cancer types for which a causal relationship with obesity could be established, the effect estimates from the Mendelian randomization studies were stronger than those seen in conventional studies, with the magnitude of risk ranging from 1.14-fold for early-life obesity and breast cancer to 1.37-fold for adult obesity and esophageal adenocarcinoma.

In another editorial accompanying the new study, Graham A. Colditz, MD, DrPH, from Washington University School of Medicine, St. Louis, underlined that childhood and adolescent obesity and their contribution to cancer risk need further attention.

“To reap the reward from past research, we must act to implement effective strategies to reduce childhood and adolescent adiposity, reduce excess weight gain in adult years, and maintain a healthy weight,” he writes.

“This will require us to change the way we live, but COVID-19 has shown we can make changes to how we live and work. Let us keep the changes we have already made, or take on new ones, that will cut our collective cancer toll,” he implores.

No funding for the study was described. Dr. Colditz is supported by the Breast Cancer Research Foundation. No other relevant financial relationships were described.

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

Federal Practitioner, in collaboration with the Association of VA Hematology/Oncology (AVAHO), present the 2022 edition of Cancer Data Trends (click to view the digital edition). This special issue provides updates on some of the top cancers and related concerns affecting veterans through original infographics and visual storytelling.

In this issue:

• Exposure-Related Cancers
• Cancer in Women
• Genitourinary Cancers
• Gastrointestinal Cancers
• Telehealth in Oncology
•  Precision Oncology
•  Palliative and Hospice Care
•  Alcohol and Cancer
•  Lung Cancer
•  Oropharyngeal Cancer
• Hematologic Cancers

Federal Practitioner and AVAHO would like to thank the following experts for their contributions to this issue:

Anita Aggarwal, DO, PhD; Sara Ahmed, PhD; Katherine Faricy-Anderson, MD; Apar Kishor Ganti, MD, MS; Solomon A Graf, MD; Kate Hendricks Thomas, PhD; Michael Kelley, MD; Mark Klein, MD, Gina McWhirter, MSN, MBA, RN; Bruce Montgomery, MD; Vida Almario Passero, MD, MBA; Thomas D Rodgers, MD; Vlad C Sandulache, MD, PhD; David H Wang, MD, PhD.

Federal Practitioner, in collaboration with the Association of VA Hematology/Oncology (AVAHO), present the 2022 edition of Cancer Data Trends (click to view the digital edition). This special issue provides updates on some of the top cancers and related concerns affecting veterans through original infographics and visual storytelling.

In this issue:

• Exposure-Related Cancers
• Cancer in Women
• Genitourinary Cancers
• Gastrointestinal Cancers
• Telehealth in Oncology
•  Precision Oncology
•  Palliative and Hospice Care
•  Alcohol and Cancer
•  Lung Cancer
•  Oropharyngeal Cancer
• Hematologic Cancers

Federal Practitioner and AVAHO would like to thank the following experts for their contributions to this issue:

Anita Aggarwal, DO, PhD; Sara Ahmed, PhD; Katherine Faricy-Anderson, MD; Apar Kishor Ganti, MD, MS; Solomon A Graf, MD; Kate Hendricks Thomas, PhD; Michael Kelley, MD; Mark Klein, MD, Gina McWhirter, MSN, MBA, RN; Bruce Montgomery, MD; Vida Almario Passero, MD, MBA; Thomas D Rodgers, MD; Vlad C Sandulache, MD, PhD; David H Wang, MD, PhD.

Federal Practitioner, in collaboration with the Association of VA Hematology/Oncology (AVAHO), present the 2022 edition of Cancer Data Trends (click to view the digital edition). This special issue provides updates on some of the top cancers and related concerns affecting veterans through original infographics and visual storytelling.

In this issue:

• Exposure-Related Cancers
• Cancer in Women
• Genitourinary Cancers
• Gastrointestinal Cancers
• Telehealth in Oncology
•  Precision Oncology
•  Palliative and Hospice Care
•  Alcohol and Cancer
•  Lung Cancer
•  Oropharyngeal Cancer
• Hematologic Cancers

Federal Practitioner and AVAHO would like to thank the following experts for their contributions to this issue:

Anita Aggarwal, DO, PhD; Sara Ahmed, PhD; Katherine Faricy-Anderson, MD; Apar Kishor Ganti, MD, MS; Solomon A Graf, MD; Kate Hendricks Thomas, PhD; Michael Kelley, MD; Mark Klein, MD, Gina McWhirter, MSN, MBA, RN; Bruce Montgomery, MD; Vida Almario Passero, MD, MBA; Thomas D Rodgers, MD; Vlad C Sandulache, MD, PhD; David H Wang, MD, PhD.

Only about 1 in 7 new cancer drugs approved in the U.S. displace existing standards of care, a new analysis shows.

Of more than 200 agents evaluated, most (42%) received approval as second-, third-, or later-line therapies.

“While there is justified enthusiasm for the high volume of new cancer drug approvals in oncology and malignant hematology, these approvals must be evaluated in the context of their use,” the authors note in a report published online March 15 in JAMA Network Open. Later-line drugs may, for instance, “benefit patients with few alternatives but also add to cost of care and further delay palliative and comfort services” compared to first-line therapies, which may alter “the treatment paradigm for a certain indication.”

The U.S. Food and Drug Administration approves several new cancer drugs each month, but it’s not clear how many transform the treatment landscape.

To investigate, David Benjamin, MD, with the Division of Hematology and Oncology, University of California, Irvine, and colleagues evaluated all 207 cancer drugs approved in the U.S. between May 1, 2016 and May 31, 2021.

The researchers found that only 28 drugs (14%) displaced the prior first-line standard of care for an indication.

Examples of these cancer drugs include alectinib for anaplastic lymphoma kinase rearrangement–positive metastatic non–small cell lung cancer (NSCLC), osimertinib for epidermal growth factor receptor exon 19 deletion or exon 21 L858R substitution NSCLC, atezolizumab plus bevacizumab for unresectable or metastatic hepatocellular carcinoma, and cabozantinib for advanced kidney cancer.

A total of 32 drugs (15%) were approved as first-line alternatives or new drugs. These drugs were approved for use in the first-line setting but did not necessarily replace the standard of care at the time of approval or were first-of-their-class therapies.

Examples of these drug approvals include apalutamide for nonmetastatic castrate-resistant prostate cancer, tepotinib for metastatic MET exon 14-skipping NSCLC, and avapritinib for unresectable or metastatic gastrointestinal stromal tumor with platelet-derived growth factor receptor alpha exon 18 variant, including D842V variant.

A total of 61 drugs (29%) were approved as add-on therapies for use in combination with a previously approved therapy or in the adjuvant or maintenance settings. These drugs “can only increase the cost of care,” the study team says.

Most new approvals (n = 86) were for use in second-, third- or later-line settings, often for patients for whom other treatment options had been exhausted.

The authors highlight disparities among approvals based on tumor type. Lung-related tumors received the most approvals (n = 37), followed by genitourinary tumors (n = 28), leukemia (n = 25), lymphoma (n = 22), breast cancer (n = 19), and gastrointestinal cancers (n = 14).

The authors note that cancer drugs considered new standards of care or approved as first-line setting alternatives could “provide market competition and work to lower cancer drug prices.”

The study was funded by a grant from Arnold Ventures.

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

Only about 1 in 7 new cancer drugs approved in the U.S. displace existing standards of care, a new analysis shows.

Of more than 200 agents evaluated, most (42%) received approval as second-, third-, or later-line therapies.

“While there is justified enthusiasm for the high volume of new cancer drug approvals in oncology and malignant hematology, these approvals must be evaluated in the context of their use,” the authors note in a report published online March 15 in JAMA Network Open. Later-line drugs may, for instance, “benefit patients with few alternatives but also add to cost of care and further delay palliative and comfort services” compared to first-line therapies, which may alter “the treatment paradigm for a certain indication.”

The U.S. Food and Drug Administration approves several new cancer drugs each month, but it’s not clear how many transform the treatment landscape.

To investigate, David Benjamin, MD, with the Division of Hematology and Oncology, University of California, Irvine, and colleagues evaluated all 207 cancer drugs approved in the U.S. between May 1, 2016 and May 31, 2021.

The researchers found that only 28 drugs (14%) displaced the prior first-line standard of care for an indication.

Examples of these cancer drugs include alectinib for anaplastic lymphoma kinase rearrangement–positive metastatic non–small cell lung cancer (NSCLC), osimertinib for epidermal growth factor receptor exon 19 deletion or exon 21 L858R substitution NSCLC, atezolizumab plus bevacizumab for unresectable or metastatic hepatocellular carcinoma, and cabozantinib for advanced kidney cancer.

A total of 32 drugs (15%) were approved as first-line alternatives or new drugs. These drugs were approved for use in the first-line setting but did not necessarily replace the standard of care at the time of approval or were first-of-their-class therapies.

Examples of these drug approvals include apalutamide for nonmetastatic castrate-resistant prostate cancer, tepotinib for metastatic MET exon 14-skipping NSCLC, and avapritinib for unresectable or metastatic gastrointestinal stromal tumor with platelet-derived growth factor receptor alpha exon 18 variant, including D842V variant.

A total of 61 drugs (29%) were approved as add-on therapies for use in combination with a previously approved therapy or in the adjuvant or maintenance settings. These drugs “can only increase the cost of care,” the study team says.

Most new approvals (n = 86) were for use in second-, third- or later-line settings, often for patients for whom other treatment options had been exhausted.

The authors highlight disparities among approvals based on tumor type. Lung-related tumors received the most approvals (n = 37), followed by genitourinary tumors (n = 28), leukemia (n = 25), lymphoma (n = 22), breast cancer (n = 19), and gastrointestinal cancers (n = 14).

The authors note that cancer drugs considered new standards of care or approved as first-line setting alternatives could “provide market competition and work to lower cancer drug prices.”

The study was funded by a grant from Arnold Ventures.

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

Only about 1 in 7 new cancer drugs approved in the U.S. displace existing standards of care, a new analysis shows.

Of more than 200 agents evaluated, most (42%) received approval as second-, third-, or later-line therapies.

“While there is justified enthusiasm for the high volume of new cancer drug approvals in oncology and malignant hematology, these approvals must be evaluated in the context of their use,” the authors note in a report published online March 15 in JAMA Network Open. Later-line drugs may, for instance, “benefit patients with few alternatives but also add to cost of care and further delay palliative and comfort services” compared to first-line therapies, which may alter “the treatment paradigm for a certain indication.”

The U.S. Food and Drug Administration approves several new cancer drugs each month, but it’s not clear how many transform the treatment landscape.

To investigate, David Benjamin, MD, with the Division of Hematology and Oncology, University of California, Irvine, and colleagues evaluated all 207 cancer drugs approved in the U.S. between May 1, 2016 and May 31, 2021.

The researchers found that only 28 drugs (14%) displaced the prior first-line standard of care for an indication.

Examples of these cancer drugs include alectinib for anaplastic lymphoma kinase rearrangement–positive metastatic non–small cell lung cancer (NSCLC), osimertinib for epidermal growth factor receptor exon 19 deletion or exon 21 L858R substitution NSCLC, atezolizumab plus bevacizumab for unresectable or metastatic hepatocellular carcinoma, and cabozantinib for advanced kidney cancer.

A total of 32 drugs (15%) were approved as first-line alternatives or new drugs. These drugs were approved for use in the first-line setting but did not necessarily replace the standard of care at the time of approval or were first-of-their-class therapies.

Examples of these drug approvals include apalutamide for nonmetastatic castrate-resistant prostate cancer, tepotinib for metastatic MET exon 14-skipping NSCLC, and avapritinib for unresectable or metastatic gastrointestinal stromal tumor with platelet-derived growth factor receptor alpha exon 18 variant, including D842V variant.

A total of 61 drugs (29%) were approved as add-on therapies for use in combination with a previously approved therapy or in the adjuvant or maintenance settings. These drugs “can only increase the cost of care,” the study team says.

Most new approvals (n = 86) were for use in second-, third- or later-line settings, often for patients for whom other treatment options had been exhausted.

The authors highlight disparities among approvals based on tumor type. Lung-related tumors received the most approvals (n = 37), followed by genitourinary tumors (n = 28), leukemia (n = 25), lymphoma (n = 22), breast cancer (n = 19), and gastrointestinal cancers (n = 14).

The authors note that cancer drugs considered new standards of care or approved as first-line setting alternatives could “provide market competition and work to lower cancer drug prices.”

The study was funded by a grant from Arnold Ventures.

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

Immune checkpoint inhibitors (ICIs) have unquestionably revolutionized the care of patients with malignant melanoma, non-small cell lung cancer, and other types of cancer.

But about 40% of patients with cancer treated with ICIs will experience immune-related dermatologic adverse events that can range from mild rashes and hair and nail changes to uncommon but life-threatening complications, such as Stevens-Johnson syndrome, a form of toxic epidermal necrolysis, according to members of a European Academy of Dermatology and Venereology (EADV) task force.

“The desirable, immune-mediated oncologic response is often achieved at the cost of immune-related adverse events (irAEs) that may potentially affect any organ system,” they write in a position statement on the management of ICI-derived dermatologic adverse events.

Recommendations from the EADV “Dermatology for Cancer Patients” task force have been published in the Journal of the European Academy of Dermatology and Venereology.

Task force members developed the recommendations based on clinical experience from published data and came up with specific recommendations for treating cutaneous toxicities associated with dermatologic immune-related adverse events (dirAEs) that occur in patients receiving immunotherapy with an ICI.

ICIs include the cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) inhibitor ipilimumab (Yervoy, Bristol Myers Squibb), and inhibitors of programmed death protein 1 (PD-1) and its ligand (PD-L1), including nivolumab (Opdivo, Bristol Myers Squibb), pembrolizumab (Keytruda, Merck), and other agents.

“The basic principle of management is that the interventions should be tailored to serve the equilibrium between patients’ relief from the symptoms and signs of skin toxicity and the preservation of an unimpeded oncologic treatment,” they write.

The recommendations are in line with those included in a 2021 update of the American Society of Clinical Oncology (ASCO) guidelines on the management of irAEs in patients treated with ICIs across the whole range of organ systems, said Milan J. Anadkat, MD, professor of dermatology and director of dermatology clinical trials at Washington University School of Medicine, St. Louis. Dr. Anadkat was a coauthor of the ASCO guideline update.

Although the European recommendations focus only on dermatologic side effects of ICIs in patients with cancer, “that doesn’t diminish their importance. They do a good job of summarizing how to approach and how to manage it depending on the severity of the toxicities and the various types of toxicities,” he told this news organization.

Having a paper focused exclusively on the dermatologic side effects of ICIs allows the inclusion of photographs that can help clinicians identify specific conditions that may require referral to a dermatologist, he said.

Both Dr. Anadkat and the authors of the European recommendations noted that dermatologic irAEs are more common with CTLA-4 inhibition than with PD-1/PD-L1 inhibition.

“It has to do with where the target is,” Dr. Anadkat said. “CTLA-4 inhibition works on a central aspect of the immune system, so it’s a much less specific site, whereas PD-1 affects an interaction at the site of the tumor cell itself, so it’s a little more specific.”

Pruritus

ICI-induced pruritus can occur without apparent skin changes, they write, noting that in a recent study of patients with dirAEs, about one-third had isolated pruritus. 

The task force members cite a meta-analysis indicating a pruritus incidence of 13.2% for patients treated with nivolumab and 20.2% for patients treated with pembrolizumab but respective grade 3 pruritus rates of only 0.5% and 2.3%. The reported incidence of pruritus with ipilimumab was 47% in a different study.

Recommended treatments include topical moisturizers with or without medium-to-high potency corticosteroids for grade 1 reactions, non-sedating histamines and/or GABA agonists such as pregabalin, or gabapentin for grade 2 pruritus, and suspension of ICIs until pruritus improves in patients with grade 3 pruritus.
 

Maculopapular rash

Maculopapular or eczema-like rashes may occur in up to 68% of patients who receive a CTLA-4 inhibitor and up to 20% of those who receive a PD1/PD-L1 inhibitor, the authors note. Rashes commonly appear within 3-6 weeks of initiating therapy.

“The clinical presentation is nonspecific and consists of a rapid onset of multiple minimally scaly, erythematous macules and papules, congregating into plaques. Lesions are mostly located on trunk and extensor surfaces of the extremities and the face is generally spared,” they write.

Maculopapular rashes are typically accompanied by itching but could be asymptomatic, they noted.

Mild (grade 1) rashes may respond to moisturizers and topical potent or super-potent corticosteroids. Patients with grade 2 rash should also receive oral antihistamines. Systemic corticosteroids may be considered for patients with grade 3 rashes but only after other dirAEs that may require specific management, such as psoriasis, are ruled out.
 

Psoriasis-like rash

The most common form of psoriasis seen in patients treated with ICIs is psoriasis vulgaris with plaques, but other clinical variants are also seen, the authors note.

“Topical agents (corticosteroids, Vitamin D analogues) are prescribed in Grades 1/2 and supplementary” to systemic treatment for patients with grade 3 or recalcitrant lesions, they write. “If skin-directed therapies fail to provide symptomatic control,” systemic treatment and narrow band UVB phototherapy “should be considered,” they add. 

Evidence regarding the use of systemic therapies to treat psoriasis-like rash associated with ICIs is sparse. Acitretin can be safely used in patients with cancer. Low-dose methotrexate is also safe to use except in patients with non-melanoma skin cancers. Cyclosporine, however, should be avoided because of the potential for tumor-promoting effects, they emphasized.

The recommendations also cover treatment of lichen planus-like and vitiligo-like rashes, as well as hair and nail changes, autoimmune bullous disorders, and oral mucosal dirAEs.

In addition, the recommendations cover severe cutaneous adverse reactions as well as serious, potentially life-threatening dirAEs, including Stevens-Johnson syndrome/TEN, acute generalized exanthematous pustulosis (AGEP), and drug reaction with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome (DRESS/DIHS).

“The dose of corticosteroids may be adapted to the severity of DRESS. The therapeutic benefit of systemic corticosteroids in the management of SJS/TEN remains controversial, and some authors favor treatment with cyclosporine. However, the use of corticosteroids in this context of ICI treatment appears reasonable and should be proposed. Short courses of steroids seem also effective in AGEP,” the task force members write.

The recommendations did not have outside funding. Of the 19 authors, 6 disclosed relationships with various pharmaceutical companies, including AbbVie, Leo Pharma, Boehringer Ingelheim, Bristol Myers Squibb, and/or Janssen. Dr. Anadkat disclosed previous relationships with Merck, Bristol Myers Squibb, and current relationships with others.

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

Immune checkpoint inhibitors (ICIs) have unquestionably revolutionized the care of patients with malignant melanoma, non-small cell lung cancer, and other types of cancer.

But about 40% of patients with cancer treated with ICIs will experience immune-related dermatologic adverse events that can range from mild rashes and hair and nail changes to uncommon but life-threatening complications, such as Stevens-Johnson syndrome, a form of toxic epidermal necrolysis, according to members of a European Academy of Dermatology and Venereology (EADV) task force.

“The desirable, immune-mediated oncologic response is often achieved at the cost of immune-related adverse events (irAEs) that may potentially affect any organ system,” they write in a position statement on the management of ICI-derived dermatologic adverse events.

Recommendations from the EADV “Dermatology for Cancer Patients” task force have been published in the Journal of the European Academy of Dermatology and Venereology.

Task force members developed the recommendations based on clinical experience from published data and came up with specific recommendations for treating cutaneous toxicities associated with dermatologic immune-related adverse events (dirAEs) that occur in patients receiving immunotherapy with an ICI.

ICIs include the cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) inhibitor ipilimumab (Yervoy, Bristol Myers Squibb), and inhibitors of programmed death protein 1 (PD-1) and its ligand (PD-L1), including nivolumab (Opdivo, Bristol Myers Squibb), pembrolizumab (Keytruda, Merck), and other agents.

“The basic principle of management is that the interventions should be tailored to serve the equilibrium between patients’ relief from the symptoms and signs of skin toxicity and the preservation of an unimpeded oncologic treatment,” they write.

The recommendations are in line with those included in a 2021 update of the American Society of Clinical Oncology (ASCO) guidelines on the management of irAEs in patients treated with ICIs across the whole range of organ systems, said Milan J. Anadkat, MD, professor of dermatology and director of dermatology clinical trials at Washington University School of Medicine, St. Louis. Dr. Anadkat was a coauthor of the ASCO guideline update.

Although the European recommendations focus only on dermatologic side effects of ICIs in patients with cancer, “that doesn’t diminish their importance. They do a good job of summarizing how to approach and how to manage it depending on the severity of the toxicities and the various types of toxicities,” he told this news organization.

Having a paper focused exclusively on the dermatologic side effects of ICIs allows the inclusion of photographs that can help clinicians identify specific conditions that may require referral to a dermatologist, he said.

Both Dr. Anadkat and the authors of the European recommendations noted that dermatologic irAEs are more common with CTLA-4 inhibition than with PD-1/PD-L1 inhibition.

“It has to do with where the target is,” Dr. Anadkat said. “CTLA-4 inhibition works on a central aspect of the immune system, so it’s a much less specific site, whereas PD-1 affects an interaction at the site of the tumor cell itself, so it’s a little more specific.”

Pruritus

ICI-induced pruritus can occur without apparent skin changes, they write, noting that in a recent study of patients with dirAEs, about one-third had isolated pruritus. 

The task force members cite a meta-analysis indicating a pruritus incidence of 13.2% for patients treated with nivolumab and 20.2% for patients treated with pembrolizumab but respective grade 3 pruritus rates of only 0.5% and 2.3%. The reported incidence of pruritus with ipilimumab was 47% in a different study.

Recommended treatments include topical moisturizers with or without medium-to-high potency corticosteroids for grade 1 reactions, non-sedating histamines and/or GABA agonists such as pregabalin, or gabapentin for grade 2 pruritus, and suspension of ICIs until pruritus improves in patients with grade 3 pruritus.
 

Maculopapular rash

Maculopapular or eczema-like rashes may occur in up to 68% of patients who receive a CTLA-4 inhibitor and up to 20% of those who receive a PD1/PD-L1 inhibitor, the authors note. Rashes commonly appear within 3-6 weeks of initiating therapy.

“The clinical presentation is nonspecific and consists of a rapid onset of multiple minimally scaly, erythematous macules and papules, congregating into plaques. Lesions are mostly located on trunk and extensor surfaces of the extremities and the face is generally spared,” they write.

Maculopapular rashes are typically accompanied by itching but could be asymptomatic, they noted.

Mild (grade 1) rashes may respond to moisturizers and topical potent or super-potent corticosteroids. Patients with grade 2 rash should also receive oral antihistamines. Systemic corticosteroids may be considered for patients with grade 3 rashes but only after other dirAEs that may require specific management, such as psoriasis, are ruled out.
 

Psoriasis-like rash

The most common form of psoriasis seen in patients treated with ICIs is psoriasis vulgaris with plaques, but other clinical variants are also seen, the authors note.

“Topical agents (corticosteroids, Vitamin D analogues) are prescribed in Grades 1/2 and supplementary” to systemic treatment for patients with grade 3 or recalcitrant lesions, they write. “If skin-directed therapies fail to provide symptomatic control,” systemic treatment and narrow band UVB phototherapy “should be considered,” they add. 

Evidence regarding the use of systemic therapies to treat psoriasis-like rash associated with ICIs is sparse. Acitretin can be safely used in patients with cancer. Low-dose methotrexate is also safe to use except in patients with non-melanoma skin cancers. Cyclosporine, however, should be avoided because of the potential for tumor-promoting effects, they emphasized.

The recommendations also cover treatment of lichen planus-like and vitiligo-like rashes, as well as hair and nail changes, autoimmune bullous disorders, and oral mucosal dirAEs.

In addition, the recommendations cover severe cutaneous adverse reactions as well as serious, potentially life-threatening dirAEs, including Stevens-Johnson syndrome/TEN, acute generalized exanthematous pustulosis (AGEP), and drug reaction with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome (DRESS/DIHS).

“The dose of corticosteroids may be adapted to the severity of DRESS. The therapeutic benefit of systemic corticosteroids in the management of SJS/TEN remains controversial, and some authors favor treatment with cyclosporine. However, the use of corticosteroids in this context of ICI treatment appears reasonable and should be proposed. Short courses of steroids seem also effective in AGEP,” the task force members write.

The recommendations did not have outside funding. Of the 19 authors, 6 disclosed relationships with various pharmaceutical companies, including AbbVie, Leo Pharma, Boehringer Ingelheim, Bristol Myers Squibb, and/or Janssen. Dr. Anadkat disclosed previous relationships with Merck, Bristol Myers Squibb, and current relationships with others.

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

Immune checkpoint inhibitors (ICIs) have unquestionably revolutionized the care of patients with malignant melanoma, non-small cell lung cancer, and other types of cancer.

But about 40% of patients with cancer treated with ICIs will experience immune-related dermatologic adverse events that can range from mild rashes and hair and nail changes to uncommon but life-threatening complications, such as Stevens-Johnson syndrome, a form of toxic epidermal necrolysis, according to members of a European Academy of Dermatology and Venereology (EADV) task force.

“The desirable, immune-mediated oncologic response is often achieved at the cost of immune-related adverse events (irAEs) that may potentially affect any organ system,” they write in a position statement on the management of ICI-derived dermatologic adverse events.

Recommendations from the EADV “Dermatology for Cancer Patients” task force have been published in the Journal of the European Academy of Dermatology and Venereology.

Task force members developed the recommendations based on clinical experience from published data and came up with specific recommendations for treating cutaneous toxicities associated with dermatologic immune-related adverse events (dirAEs) that occur in patients receiving immunotherapy with an ICI.

ICIs include the cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) inhibitor ipilimumab (Yervoy, Bristol Myers Squibb), and inhibitors of programmed death protein 1 (PD-1) and its ligand (PD-L1), including nivolumab (Opdivo, Bristol Myers Squibb), pembrolizumab (Keytruda, Merck), and other agents.

“The basic principle of management is that the interventions should be tailored to serve the equilibrium between patients’ relief from the symptoms and signs of skin toxicity and the preservation of an unimpeded oncologic treatment,” they write.

The recommendations are in line with those included in a 2021 update of the American Society of Clinical Oncology (ASCO) guidelines on the management of irAEs in patients treated with ICIs across the whole range of organ systems, said Milan J. Anadkat, MD, professor of dermatology and director of dermatology clinical trials at Washington University School of Medicine, St. Louis. Dr. Anadkat was a coauthor of the ASCO guideline update.

Although the European recommendations focus only on dermatologic side effects of ICIs in patients with cancer, “that doesn’t diminish their importance. They do a good job of summarizing how to approach and how to manage it depending on the severity of the toxicities and the various types of toxicities,” he told this news organization.

Having a paper focused exclusively on the dermatologic side effects of ICIs allows the inclusion of photographs that can help clinicians identify specific conditions that may require referral to a dermatologist, he said.

Both Dr. Anadkat and the authors of the European recommendations noted that dermatologic irAEs are more common with CTLA-4 inhibition than with PD-1/PD-L1 inhibition.

“It has to do with where the target is,” Dr. Anadkat said. “CTLA-4 inhibition works on a central aspect of the immune system, so it’s a much less specific site, whereas PD-1 affects an interaction at the site of the tumor cell itself, so it’s a little more specific.”

Pruritus

ICI-induced pruritus can occur without apparent skin changes, they write, noting that in a recent study of patients with dirAEs, about one-third had isolated pruritus. 

The task force members cite a meta-analysis indicating a pruritus incidence of 13.2% for patients treated with nivolumab and 20.2% for patients treated with pembrolizumab but respective grade 3 pruritus rates of only 0.5% and 2.3%. The reported incidence of pruritus with ipilimumab was 47% in a different study.

Recommended treatments include topical moisturizers with or without medium-to-high potency corticosteroids for grade 1 reactions, non-sedating histamines and/or GABA agonists such as pregabalin, or gabapentin for grade 2 pruritus, and suspension of ICIs until pruritus improves in patients with grade 3 pruritus.
 

Maculopapular rash

Maculopapular or eczema-like rashes may occur in up to 68% of patients who receive a CTLA-4 inhibitor and up to 20% of those who receive a PD1/PD-L1 inhibitor, the authors note. Rashes commonly appear within 3-6 weeks of initiating therapy.

“The clinical presentation is nonspecific and consists of a rapid onset of multiple minimally scaly, erythematous macules and papules, congregating into plaques. Lesions are mostly located on trunk and extensor surfaces of the extremities and the face is generally spared,” they write.

Maculopapular rashes are typically accompanied by itching but could be asymptomatic, they noted.

Mild (grade 1) rashes may respond to moisturizers and topical potent or super-potent corticosteroids. Patients with grade 2 rash should also receive oral antihistamines. Systemic corticosteroids may be considered for patients with grade 3 rashes but only after other dirAEs that may require specific management, such as psoriasis, are ruled out.
 

Psoriasis-like rash

The most common form of psoriasis seen in patients treated with ICIs is psoriasis vulgaris with plaques, but other clinical variants are also seen, the authors note.

“Topical agents (corticosteroids, Vitamin D analogues) are prescribed in Grades 1/2 and supplementary” to systemic treatment for patients with grade 3 or recalcitrant lesions, they write. “If skin-directed therapies fail to provide symptomatic control,” systemic treatment and narrow band UVB phototherapy “should be considered,” they add. 

Evidence regarding the use of systemic therapies to treat psoriasis-like rash associated with ICIs is sparse. Acitretin can be safely used in patients with cancer. Low-dose methotrexate is also safe to use except in patients with non-melanoma skin cancers. Cyclosporine, however, should be avoided because of the potential for tumor-promoting effects, they emphasized.

The recommendations also cover treatment of lichen planus-like and vitiligo-like rashes, as well as hair and nail changes, autoimmune bullous disorders, and oral mucosal dirAEs.

In addition, the recommendations cover severe cutaneous adverse reactions as well as serious, potentially life-threatening dirAEs, including Stevens-Johnson syndrome/TEN, acute generalized exanthematous pustulosis (AGEP), and drug reaction with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome (DRESS/DIHS).

“The dose of corticosteroids may be adapted to the severity of DRESS. The therapeutic benefit of systemic corticosteroids in the management of SJS/TEN remains controversial, and some authors favor treatment with cyclosporine. However, the use of corticosteroids in this context of ICI treatment appears reasonable and should be proposed. Short courses of steroids seem also effective in AGEP,” the task force members write.

The recommendations did not have outside funding. Of the 19 authors, 6 disclosed relationships with various pharmaceutical companies, including AbbVie, Leo Pharma, Boehringer Ingelheim, Bristol Myers Squibb, and/or Janssen. Dr. Anadkat disclosed previous relationships with Merck, Bristol Myers Squibb, and current relationships with others.

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