AVAHO

Currently, more than 3.8 million breast cancer survivors reside in the United States, reflecting high prevalence as well as cure rates for this common malignancy.

When over-the-counter measures including vaginal lubricants and moisturizers are not adequate, vaginal estrogen may be a highly effective treatment for genitourinary syndrome of menopause (GSM), a common condition associated with hypoestrogenism that impairs sexual function and quality of life.

Use of vaginal formulations does not result in systemic levels of estrogen above the normal postmenopausal range. Nonetheless, the U.S. Food and Drug Administration lists a history of breast cancer as a contraindication to the use of all systemic as well as vaginal estrogens.

In premenopausal women, chemotherapy for breast cancer often results in early menopause. Aromatase inhibitors, although effective in preventing recurrent disease in menopausal women, exacerbate GSM. These factors result in a high prevalence of GSM in breast cancer survivors.

Because the safety of vaginal estrogen in the setting of breast cancer is uncertain, investigators at Johns Hopkins conducted a cohort study using claims-based data from more than 200 million U.S. patients that identified women with GSM who had previously been diagnosed with breast cancer. Among some 42,000 women diagnosed with GSM after breast cancer, 5% had three or more prescriptions and were considered vaginal estrogen users.

No significant differences were noted in recurrence-free survival between the vaginal estrogen group and the no estrogen group. At 5 and 10 years of follow-up, use of vaginal estrogen was not associated with higher all-cause mortality. Among women with estrogen receptor–positive tumors, risk for breast cancer recurrence was similar between estrogen users and nonusers.

However, concomitant use of vaginal estrogen and aromatase inhibitors was associated with a higher risk for breast cancer recurrence than was use of vaginal estrogen alone.

Although this important study’s findings have the limitations characteristic of observational studies, its large size and careful analyses suggest that in selected well-counseled breast cancer survivors, off-label use of vaginal estrogen may safely improve their sexual function and quality of life.

Dr. Kaunitz is associate chairman, department of obstetrics and gynecology, University of Florida College of Medicine, Jacksonville. This transcript has been edited for clarity. A version of this article first appeared on Medscape.com.

Currently, more than 3.8 million breast cancer survivors reside in the United States, reflecting high prevalence as well as cure rates for this common malignancy.

When over-the-counter measures including vaginal lubricants and moisturizers are not adequate, vaginal estrogen may be a highly effective treatment for genitourinary syndrome of menopause (GSM), a common condition associated with hypoestrogenism that impairs sexual function and quality of life.

Use of vaginal formulations does not result in systemic levels of estrogen above the normal postmenopausal range. Nonetheless, the U.S. Food and Drug Administration lists a history of breast cancer as a contraindication to the use of all systemic as well as vaginal estrogens.

In premenopausal women, chemotherapy for breast cancer often results in early menopause. Aromatase inhibitors, although effective in preventing recurrent disease in menopausal women, exacerbate GSM. These factors result in a high prevalence of GSM in breast cancer survivors.

Because the safety of vaginal estrogen in the setting of breast cancer is uncertain, investigators at Johns Hopkins conducted a cohort study using claims-based data from more than 200 million U.S. patients that identified women with GSM who had previously been diagnosed with breast cancer. Among some 42,000 women diagnosed with GSM after breast cancer, 5% had three or more prescriptions and were considered vaginal estrogen users.

No significant differences were noted in recurrence-free survival between the vaginal estrogen group and the no estrogen group. At 5 and 10 years of follow-up, use of vaginal estrogen was not associated with higher all-cause mortality. Among women with estrogen receptor–positive tumors, risk for breast cancer recurrence was similar between estrogen users and nonusers.

However, concomitant use of vaginal estrogen and aromatase inhibitors was associated with a higher risk for breast cancer recurrence than was use of vaginal estrogen alone.

Although this important study’s findings have the limitations characteristic of observational studies, its large size and careful analyses suggest that in selected well-counseled breast cancer survivors, off-label use of vaginal estrogen may safely improve their sexual function and quality of life.

Dr. Kaunitz is associate chairman, department of obstetrics and gynecology, University of Florida College of Medicine, Jacksonville. This transcript has been edited for clarity. A version of this article first appeared on Medscape.com.

Currently, more than 3.8 million breast cancer survivors reside in the United States, reflecting high prevalence as well as cure rates for this common malignancy.

When over-the-counter measures including vaginal lubricants and moisturizers are not adequate, vaginal estrogen may be a highly effective treatment for genitourinary syndrome of menopause (GSM), a common condition associated with hypoestrogenism that impairs sexual function and quality of life.

Use of vaginal formulations does not result in systemic levels of estrogen above the normal postmenopausal range. Nonetheless, the U.S. Food and Drug Administration lists a history of breast cancer as a contraindication to the use of all systemic as well as vaginal estrogens.

In premenopausal women, chemotherapy for breast cancer often results in early menopause. Aromatase inhibitors, although effective in preventing recurrent disease in menopausal women, exacerbate GSM. These factors result in a high prevalence of GSM in breast cancer survivors.

Because the safety of vaginal estrogen in the setting of breast cancer is uncertain, investigators at Johns Hopkins conducted a cohort study using claims-based data from more than 200 million U.S. patients that identified women with GSM who had previously been diagnosed with breast cancer. Among some 42,000 women diagnosed with GSM after breast cancer, 5% had three or more prescriptions and were considered vaginal estrogen users.

No significant differences were noted in recurrence-free survival between the vaginal estrogen group and the no estrogen group. At 5 and 10 years of follow-up, use of vaginal estrogen was not associated with higher all-cause mortality. Among women with estrogen receptor–positive tumors, risk for breast cancer recurrence was similar between estrogen users and nonusers.

However, concomitant use of vaginal estrogen and aromatase inhibitors was associated with a higher risk for breast cancer recurrence than was use of vaginal estrogen alone.

Although this important study’s findings have the limitations characteristic of observational studies, its large size and careful analyses suggest that in selected well-counseled breast cancer survivors, off-label use of vaginal estrogen may safely improve their sexual function and quality of life.

Dr. Kaunitz is associate chairman, department of obstetrics and gynecology, University of Florida College of Medicine, Jacksonville. This transcript has been edited for clarity. A version of this article first appeared on Medscape.com.

Fear and a lack of health-related knowledge pose significant barriers to preventative cancer care access and effectiveness, recent survey data from The Harris Poll suggests.

The survey, commissioned by Bayer U.S. to identify patient behaviors and care barriers, indicates that more than one in four adults in the United States (27%) would rather not know if they have cancer, and nearly a third (31%) – particularly younger patients aged 18-44 years – avoid going to the doctor because they are afraid of what they might learn.

Similarly, 26% of 2,079 respondents said that fear and anxiety are the main reasons why they don’t make or keep doctor appointments. Those with lower household income and education levels, those with children under age 18 years, and Hispanic adults were most likely to cite this reason.

Almost half (up to 49%) lacked knowledge about certain cancers and risk factors.

For example, 48% of respondents were unaware that breast density affects breast cancer risk and diagnosis, and 38% said they were not very knowledgeable about breast cancer.

Regarding prostate cancer, 49% were unaware that race impacts risk and 49% said they were not knowledgeable about the disease.

The survey highlighted a lack of trust in treatments and health care processes among most adults, especially those with lower income and education levels. Overall, 53% said they have little or no trust in treatments developed by pharmaceutical companies, and 31% said they have little or no trust in medical tests, test results, and other medical processes.

The findings of the survey, which was conducted online June 6-8, 2023, among U.S. adults aged 18 years and older, underscore the need to better educate individuals about cancer risk factors and the benefits of preventative care.

“The increase of fear and anxiety, heightened by a lack of education and in some cases trust barriers, creates an environment where people may not access basic preventative care to ensure early diagnosis,” Sebastian Guth, president of Bayer U.S. and Pharmaceuticals North America, stated in a press release. “This is compounded by the fact that around 27.4 million people of all ages (8.3%) don’t have access to health insurance.

“Companies like Bayer have a responsibility to provide resources that increase health education on the importance of understanding disease risks, early disease screenings, and preventative health care,” Mr. Guth added, noting that the company is partnering with multiple patient advocacy groups to increase trust, awareness, and knowledge “to help individuals understand the resources available to them and their risks for a specific disease.”

Public health initiatives have had mixed results with respect to changing patient behaviors over time, but Breast Cancer Awareness Month (BCAM) in October of each year is a stand-out initiative that could serve as a model for other patient education initiatives, according to a 2022 study.

The Google trends analysis showed that from 2012 to 2021, BCAM was associated with improved public awareness of breast cancer, whereas Lung Cancer Awareness Month and Prostate Cancer Awareness Month had no impact on lung and prostate cancer awareness, respectively, over time, reported Yoshita Nishimura, MD, of Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences in Japan, and Jared D. Acoba, MD, of the University of Hawaii, Honolulu.

Dr. Nishimura and Dr. Acoba concluded that the success of BCAM, which was launched in 1985 and is now led by the National Breast Cancer Foundation, is likely a result of “the effective involvement of non-medical industries, influencers affected by breast cancer, and an awareness symbol.”

As for the role of physicians in raising awareness and increasing knowledge at the patient level, various guidelines focus on assessing patient needs and readiness to learn, communicating clearly, and identifying barriers, such as a lack of support and low health literacy.

An American Society of Clinical Oncology consensus guideline for physician-patient communication, for example, provides guidance on core communication skills that apply across the continuum of care, as well as specific topics to address, such as patient goals, treatment options, and support systems – all with an eye toward using “effective communication to optimize the patient-clinician relationship, patient and clinician well-being and family well-being.”

Fear and a lack of health-related knowledge pose significant barriers to preventative cancer care access and effectiveness, recent survey data from The Harris Poll suggests.

The survey, commissioned by Bayer U.S. to identify patient behaviors and care barriers, indicates that more than one in four adults in the United States (27%) would rather not know if they have cancer, and nearly a third (31%) – particularly younger patients aged 18-44 years – avoid going to the doctor because they are afraid of what they might learn.

Similarly, 26% of 2,079 respondents said that fear and anxiety are the main reasons why they don’t make or keep doctor appointments. Those with lower household income and education levels, those with children under age 18 years, and Hispanic adults were most likely to cite this reason.

Almost half (up to 49%) lacked knowledge about certain cancers and risk factors.

For example, 48% of respondents were unaware that breast density affects breast cancer risk and diagnosis, and 38% said they were not very knowledgeable about breast cancer.

Regarding prostate cancer, 49% were unaware that race impacts risk and 49% said they were not knowledgeable about the disease.

The survey highlighted a lack of trust in treatments and health care processes among most adults, especially those with lower income and education levels. Overall, 53% said they have little or no trust in treatments developed by pharmaceutical companies, and 31% said they have little or no trust in medical tests, test results, and other medical processes.

The findings of the survey, which was conducted online June 6-8, 2023, among U.S. adults aged 18 years and older, underscore the need to better educate individuals about cancer risk factors and the benefits of preventative care.

“The increase of fear and anxiety, heightened by a lack of education and in some cases trust barriers, creates an environment where people may not access basic preventative care to ensure early diagnosis,” Sebastian Guth, president of Bayer U.S. and Pharmaceuticals North America, stated in a press release. “This is compounded by the fact that around 27.4 million people of all ages (8.3%) don’t have access to health insurance.

“Companies like Bayer have a responsibility to provide resources that increase health education on the importance of understanding disease risks, early disease screenings, and preventative health care,” Mr. Guth added, noting that the company is partnering with multiple patient advocacy groups to increase trust, awareness, and knowledge “to help individuals understand the resources available to them and their risks for a specific disease.”

Public health initiatives have had mixed results with respect to changing patient behaviors over time, but Breast Cancer Awareness Month (BCAM) in October of each year is a stand-out initiative that could serve as a model for other patient education initiatives, according to a 2022 study.

The Google trends analysis showed that from 2012 to 2021, BCAM was associated with improved public awareness of breast cancer, whereas Lung Cancer Awareness Month and Prostate Cancer Awareness Month had no impact on lung and prostate cancer awareness, respectively, over time, reported Yoshita Nishimura, MD, of Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences in Japan, and Jared D. Acoba, MD, of the University of Hawaii, Honolulu.

Dr. Nishimura and Dr. Acoba concluded that the success of BCAM, which was launched in 1985 and is now led by the National Breast Cancer Foundation, is likely a result of “the effective involvement of non-medical industries, influencers affected by breast cancer, and an awareness symbol.”

As for the role of physicians in raising awareness and increasing knowledge at the patient level, various guidelines focus on assessing patient needs and readiness to learn, communicating clearly, and identifying barriers, such as a lack of support and low health literacy.

An American Society of Clinical Oncology consensus guideline for physician-patient communication, for example, provides guidance on core communication skills that apply across the continuum of care, as well as specific topics to address, such as patient goals, treatment options, and support systems – all with an eye toward using “effective communication to optimize the patient-clinician relationship, patient and clinician well-being and family well-being.”

Fear and a lack of health-related knowledge pose significant barriers to preventative cancer care access and effectiveness, recent survey data from The Harris Poll suggests.

The survey, commissioned by Bayer U.S. to identify patient behaviors and care barriers, indicates that more than one in four adults in the United States (27%) would rather not know if they have cancer, and nearly a third (31%) – particularly younger patients aged 18-44 years – avoid going to the doctor because they are afraid of what they might learn.

Similarly, 26% of 2,079 respondents said that fear and anxiety are the main reasons why they don’t make or keep doctor appointments. Those with lower household income and education levels, those with children under age 18 years, and Hispanic adults were most likely to cite this reason.

Almost half (up to 49%) lacked knowledge about certain cancers and risk factors.

For example, 48% of respondents were unaware that breast density affects breast cancer risk and diagnosis, and 38% said they were not very knowledgeable about breast cancer.

Regarding prostate cancer, 49% were unaware that race impacts risk and 49% said they were not knowledgeable about the disease.

The survey highlighted a lack of trust in treatments and health care processes among most adults, especially those with lower income and education levels. Overall, 53% said they have little or no trust in treatments developed by pharmaceutical companies, and 31% said they have little or no trust in medical tests, test results, and other medical processes.

The findings of the survey, which was conducted online June 6-8, 2023, among U.S. adults aged 18 years and older, underscore the need to better educate individuals about cancer risk factors and the benefits of preventative care.

“The increase of fear and anxiety, heightened by a lack of education and in some cases trust barriers, creates an environment where people may not access basic preventative care to ensure early diagnosis,” Sebastian Guth, president of Bayer U.S. and Pharmaceuticals North America, stated in a press release. “This is compounded by the fact that around 27.4 million people of all ages (8.3%) don’t have access to health insurance.

“Companies like Bayer have a responsibility to provide resources that increase health education on the importance of understanding disease risks, early disease screenings, and preventative health care,” Mr. Guth added, noting that the company is partnering with multiple patient advocacy groups to increase trust, awareness, and knowledge “to help individuals understand the resources available to them and their risks for a specific disease.”

Public health initiatives have had mixed results with respect to changing patient behaviors over time, but Breast Cancer Awareness Month (BCAM) in October of each year is a stand-out initiative that could serve as a model for other patient education initiatives, according to a 2022 study.

The Google trends analysis showed that from 2012 to 2021, BCAM was associated with improved public awareness of breast cancer, whereas Lung Cancer Awareness Month and Prostate Cancer Awareness Month had no impact on lung and prostate cancer awareness, respectively, over time, reported Yoshita Nishimura, MD, of Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences in Japan, and Jared D. Acoba, MD, of the University of Hawaii, Honolulu.

Dr. Nishimura and Dr. Acoba concluded that the success of BCAM, which was launched in 1985 and is now led by the National Breast Cancer Foundation, is likely a result of “the effective involvement of non-medical industries, influencers affected by breast cancer, and an awareness symbol.”

As for the role of physicians in raising awareness and increasing knowledge at the patient level, various guidelines focus on assessing patient needs and readiness to learn, communicating clearly, and identifying barriers, such as a lack of support and low health literacy.

An American Society of Clinical Oncology consensus guideline for physician-patient communication, for example, provides guidance on core communication skills that apply across the continuum of care, as well as specific topics to address, such as patient goals, treatment options, and support systems – all with an eye toward using “effective communication to optimize the patient-clinician relationship, patient and clinician well-being and family well-being.”

Proposed updates to the tumor-node-metastasis (TNM) classification for lung cancer will affect the way patients are staged, experts say.

The updates for the 9th edition of the TNM Classification of Malignant Tumors: Lung Cancer were presented at the annual World Conference on Lung Cancer. The final version will be published Jan. 1, 2024.

The core proposed change, according to Hisao Asamura, MD, chair of the IASLC Staging and Prognostic Factors Committee, is to divide N2 and M1c disease into two subcategories, while leaving the T descriptors unchanged.

This update is based on large survival differences among patients with these tumor characteristics, following an analysis of outcomes in more than 87,000 individuals diagnosed with lung cancer.

Session cochair Ramón Rami-Porta, MD, PhD, explained that previous editions of the classification were based on “pathologic stage, not clinical stage” but ultimately “we could not validate those findings” clinically.

“This is the first time that some sort of very simple quantification” of lung tumors “could be validated at the clinical stage as well,” which means that clinical staging can improve all over the world, said Dr. Rami-Porta, medical oncologist at Hospital Universitari Mútua Terrassa (Spain).

Session cochair Paul Van Schil, MD, PhD, of Antwerp (the Netherlands) University Hospital explained that the proposed changes reflect what clinicians already see in their daily practice.

The latest TNM classification included data submitted on 124,581 patients diagnosed with lung cancer between 2011 and 2019, 56% of whom were from Asia/Australia, 25% from Europe, and 16% from North America.

Overall, 87,339 patients were included in the analysis – 83% with non–small cell lung cancer (NSCLC) and 7% with small cell lung cancer (SCLC). Most (62%) underwent surgery, either alone (47%), alongside chemotherapy (13%), or plus radiotherapy (2%). A minority (13%) received chemotherapy alone, and 13% received all three modalities.

The committee working on the update to the TNM classification had 112 members and comprised 14 subcommittees, which focused on different aspects of diagnosing and assessing the disease.

The committee agreed there should be no changes to the T category in the upcoming 9th Edition.

Evaluating the T category, some members expressed concern that patients with T3 disease embedded in the chest wall have worse survival outcomes than those with other forms of T3 disease. But, Dr. Asamura explained, the pathological versus clinical findings were inconsistent.

On pathological assessment, patients with T3 disease in the chest wall had a worse prognosis but clinical assessment indicated no survival difference. Given the lack of consensus, “we do not recommend any changes” to the current criteria, said Dr. Asamura.

Turning to the N category, Dr. Asamura explained that N2 disease will be divided into two subcategories: N2a, categorized by single N2 station involvement, and N2b, defined as multiple N2 station involvement.

Further analysis indicated that the estimated 5-year survival was significantly worse for patients with N2b disease on clinical assessment (31% vs. 42% with N2a disease; hazard ratio for death, 1.27; P < .0001) and on pathological assessment (HR, 1.46; P < .0001).

The committee also proposed a change to the M category, dividing M1c disease into two subcategories:

• M1c1 – defined as multiple extrathoracic metastases in a single organ system
• M1c2 – defined as multiple extrathoracic metastases in multiple organ systems

This change was driven by estimates of 5-year survival among patients with M1c1 (27%) versus M1c2 disease (19%). Compared with M1b disease, M1c1 was associated with a lower risk for death than M1c2 disease (HR, 1.27 vs. 1.39).

These changes, particularly those for the N category, will have a notable impact on how patients are staged, Dr. Asamura said.

Dividing the N2 category into N2a and N2b disease will push patients with T1, N1 disease from the IIB category (8th edition) to the IIA category (9th edition). The 8th edition categorized all T1, N2 patients as IIIA but the new edition would categorize patients with T1, N2a disease as IIB overall and those with N2b disease as IIIA. And patients with T2, N2a disease will be staged as IIIA — the same category as T2, N2 disease in the 8th edition – while those with N2b disease will be staged as IIIB.

By contrast, the division of M1c into M1c1 and M1c2 disease will not affect a patient’s overall stage, which will be IVB in all cases.

Upal Basu Roy, PhD, MPH, who was not part of the committee, said the TNM classification stage of cancers is “incredibly important in cataloguing the extent of disease” and to “decide the optimal treatment option.”

TNM classification is also “used to describe the burden of disease to be eligible for a clinical trial,” said Dr. Roy, executive director of research, LUNGevity Foundation, Chicago.

The changes in N staging may require sampling more lymph nodes than the current sampling frame of six, Dr. Roy said, adding that “surgeons and pathologists may need to be educated about the need for additional sampling.”

The subcategories for M1c disease will also need to be aligned with definitions of oligometastatic disease. “This is critical,” Dr. Roy said, as this staging may affect treatment choices.

No funding was declared. Dr. Asamura declares relationships with Medtronic, Taiho Pharmaceutical, Johnson & Johnson, Lily, Astellas, and Ono Pharmaceutical. Dr. Roy declared no relevant financial relationships.

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

Proposed updates to the tumor-node-metastasis (TNM) classification for lung cancer will affect the way patients are staged, experts say.

The updates for the 9th edition of the TNM Classification of Malignant Tumors: Lung Cancer were presented at the annual World Conference on Lung Cancer. The final version will be published Jan. 1, 2024.

The core proposed change, according to Hisao Asamura, MD, chair of the IASLC Staging and Prognostic Factors Committee, is to divide N2 and M1c disease into two subcategories, while leaving the T descriptors unchanged.

This update is based on large survival differences among patients with these tumor characteristics, following an analysis of outcomes in more than 87,000 individuals diagnosed with lung cancer.

Session cochair Ramón Rami-Porta, MD, PhD, explained that previous editions of the classification were based on “pathologic stage, not clinical stage” but ultimately “we could not validate those findings” clinically.

“This is the first time that some sort of very simple quantification” of lung tumors “could be validated at the clinical stage as well,” which means that clinical staging can improve all over the world, said Dr. Rami-Porta, medical oncologist at Hospital Universitari Mútua Terrassa (Spain).

Session cochair Paul Van Schil, MD, PhD, of Antwerp (the Netherlands) University Hospital explained that the proposed changes reflect what clinicians already see in their daily practice.

The latest TNM classification included data submitted on 124,581 patients diagnosed with lung cancer between 2011 and 2019, 56% of whom were from Asia/Australia, 25% from Europe, and 16% from North America.

Overall, 87,339 patients were included in the analysis – 83% with non–small cell lung cancer (NSCLC) and 7% with small cell lung cancer (SCLC). Most (62%) underwent surgery, either alone (47%), alongside chemotherapy (13%), or plus radiotherapy (2%). A minority (13%) received chemotherapy alone, and 13% received all three modalities.

The committee working on the update to the TNM classification had 112 members and comprised 14 subcommittees, which focused on different aspects of diagnosing and assessing the disease.

The committee agreed there should be no changes to the T category in the upcoming 9th Edition.

Evaluating the T category, some members expressed concern that patients with T3 disease embedded in the chest wall have worse survival outcomes than those with other forms of T3 disease. But, Dr. Asamura explained, the pathological versus clinical findings were inconsistent.

On pathological assessment, patients with T3 disease in the chest wall had a worse prognosis but clinical assessment indicated no survival difference. Given the lack of consensus, “we do not recommend any changes” to the current criteria, said Dr. Asamura.

Turning to the N category, Dr. Asamura explained that N2 disease will be divided into two subcategories: N2a, categorized by single N2 station involvement, and N2b, defined as multiple N2 station involvement.

Further analysis indicated that the estimated 5-year survival was significantly worse for patients with N2b disease on clinical assessment (31% vs. 42% with N2a disease; hazard ratio for death, 1.27; P < .0001) and on pathological assessment (HR, 1.46; P < .0001).

The committee also proposed a change to the M category, dividing M1c disease into two subcategories:

• M1c1 – defined as multiple extrathoracic metastases in a single organ system
• M1c2 – defined as multiple extrathoracic metastases in multiple organ systems

This change was driven by estimates of 5-year survival among patients with M1c1 (27%) versus M1c2 disease (19%). Compared with M1b disease, M1c1 was associated with a lower risk for death than M1c2 disease (HR, 1.27 vs. 1.39).

These changes, particularly those for the N category, will have a notable impact on how patients are staged, Dr. Asamura said.

Dividing the N2 category into N2a and N2b disease will push patients with T1, N1 disease from the IIB category (8th edition) to the IIA category (9th edition). The 8th edition categorized all T1, N2 patients as IIIA but the new edition would categorize patients with T1, N2a disease as IIB overall and those with N2b disease as IIIA. And patients with T2, N2a disease will be staged as IIIA — the same category as T2, N2 disease in the 8th edition – while those with N2b disease will be staged as IIIB.

By contrast, the division of M1c into M1c1 and M1c2 disease will not affect a patient’s overall stage, which will be IVB in all cases.

Upal Basu Roy, PhD, MPH, who was not part of the committee, said the TNM classification stage of cancers is “incredibly important in cataloguing the extent of disease” and to “decide the optimal treatment option.”

TNM classification is also “used to describe the burden of disease to be eligible for a clinical trial,” said Dr. Roy, executive director of research, LUNGevity Foundation, Chicago.

The changes in N staging may require sampling more lymph nodes than the current sampling frame of six, Dr. Roy said, adding that “surgeons and pathologists may need to be educated about the need for additional sampling.”

The subcategories for M1c disease will also need to be aligned with definitions of oligometastatic disease. “This is critical,” Dr. Roy said, as this staging may affect treatment choices.

No funding was declared. Dr. Asamura declares relationships with Medtronic, Taiho Pharmaceutical, Johnson & Johnson, Lily, Astellas, and Ono Pharmaceutical. Dr. Roy declared no relevant financial relationships.

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

Proposed updates to the tumor-node-metastasis (TNM) classification for lung cancer will affect the way patients are staged, experts say.

The updates for the 9th edition of the TNM Classification of Malignant Tumors: Lung Cancer were presented at the annual World Conference on Lung Cancer. The final version will be published Jan. 1, 2024.

The core proposed change, according to Hisao Asamura, MD, chair of the IASLC Staging and Prognostic Factors Committee, is to divide N2 and M1c disease into two subcategories, while leaving the T descriptors unchanged.

This update is based on large survival differences among patients with these tumor characteristics, following an analysis of outcomes in more than 87,000 individuals diagnosed with lung cancer.

Session cochair Ramón Rami-Porta, MD, PhD, explained that previous editions of the classification were based on “pathologic stage, not clinical stage” but ultimately “we could not validate those findings” clinically.

“This is the first time that some sort of very simple quantification” of lung tumors “could be validated at the clinical stage as well,” which means that clinical staging can improve all over the world, said Dr. Rami-Porta, medical oncologist at Hospital Universitari Mútua Terrassa (Spain).

Session cochair Paul Van Schil, MD, PhD, of Antwerp (the Netherlands) University Hospital explained that the proposed changes reflect what clinicians already see in their daily practice.

The latest TNM classification included data submitted on 124,581 patients diagnosed with lung cancer between 2011 and 2019, 56% of whom were from Asia/Australia, 25% from Europe, and 16% from North America.

Overall, 87,339 patients were included in the analysis – 83% with non–small cell lung cancer (NSCLC) and 7% with small cell lung cancer (SCLC). Most (62%) underwent surgery, either alone (47%), alongside chemotherapy (13%), or plus radiotherapy (2%). A minority (13%) received chemotherapy alone, and 13% received all three modalities.

The committee working on the update to the TNM classification had 112 members and comprised 14 subcommittees, which focused on different aspects of diagnosing and assessing the disease.

The committee agreed there should be no changes to the T category in the upcoming 9th Edition.

Evaluating the T category, some members expressed concern that patients with T3 disease embedded in the chest wall have worse survival outcomes than those with other forms of T3 disease. But, Dr. Asamura explained, the pathological versus clinical findings were inconsistent.

On pathological assessment, patients with T3 disease in the chest wall had a worse prognosis but clinical assessment indicated no survival difference. Given the lack of consensus, “we do not recommend any changes” to the current criteria, said Dr. Asamura.

Turning to the N category, Dr. Asamura explained that N2 disease will be divided into two subcategories: N2a, categorized by single N2 station involvement, and N2b, defined as multiple N2 station involvement.

Further analysis indicated that the estimated 5-year survival was significantly worse for patients with N2b disease on clinical assessment (31% vs. 42% with N2a disease; hazard ratio for death, 1.27; P < .0001) and on pathological assessment (HR, 1.46; P < .0001).

The committee also proposed a change to the M category, dividing M1c disease into two subcategories:

• M1c1 – defined as multiple extrathoracic metastases in a single organ system
• M1c2 – defined as multiple extrathoracic metastases in multiple organ systems

This change was driven by estimates of 5-year survival among patients with M1c1 (27%) versus M1c2 disease (19%). Compared with M1b disease, M1c1 was associated with a lower risk for death than M1c2 disease (HR, 1.27 vs. 1.39).

These changes, particularly those for the N category, will have a notable impact on how patients are staged, Dr. Asamura said.

Dividing the N2 category into N2a and N2b disease will push patients with T1, N1 disease from the IIB category (8th edition) to the IIA category (9th edition). The 8th edition categorized all T1, N2 patients as IIIA but the new edition would categorize patients with T1, N2a disease as IIB overall and those with N2b disease as IIIA. And patients with T2, N2a disease will be staged as IIIA — the same category as T2, N2 disease in the 8th edition – while those with N2b disease will be staged as IIIB.

By contrast, the division of M1c into M1c1 and M1c2 disease will not affect a patient’s overall stage, which will be IVB in all cases.

Upal Basu Roy, PhD, MPH, who was not part of the committee, said the TNM classification stage of cancers is “incredibly important in cataloguing the extent of disease” and to “decide the optimal treatment option.”

TNM classification is also “used to describe the burden of disease to be eligible for a clinical trial,” said Dr. Roy, executive director of research, LUNGevity Foundation, Chicago.

The changes in N staging may require sampling more lymph nodes than the current sampling frame of six, Dr. Roy said, adding that “surgeons and pathologists may need to be educated about the need for additional sampling.”

The subcategories for M1c disease will also need to be aligned with definitions of oligometastatic disease. “This is critical,” Dr. Roy said, as this staging may affect treatment choices.

No funding was declared. Dr. Asamura declares relationships with Medtronic, Taiho Pharmaceutical, Johnson & Johnson, Lily, Astellas, and Ono Pharmaceutical. Dr. Roy declared no relevant financial relationships.

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

INTRODUCTION

Urinary bladder is an extremely rare site of extrapulmonary small cell cancer (EPSCC). Unlike small cell lung cancer (SCLC), there is no clear guideline for prophylactic cranial irradiation (PCI) for EPSCC. In this case report and literature review, we discuss small cell cancer of urinary bladder (SCCUB) and the role of PCI in SCCUB.

CASE PRESENTATION

A 74-year-old male presented with gross hematuria and an unremarkable physical examination. CT showed 1.7 cm right anterolateral bladder wall thickening. Cystoscopy revealed a 2-3 cm high-grade bladder lesion. Pathology from transurethral resection of the tumor was consistent with T1N0M0 small cell carcinoma. MRI brain and FDG-PET showed no extravesical disease. Patient received four cycles of neoadjuvant carboplatin/etoposide per his preference as he wanted to protect his hearing due to his profession followed by radical cystoprostatectomy. Post-op pathology showed clear margins. We decided to forego PCI in favor of interval surveillance with MRI and follow- up images remain negative for distant metastases.

DISCUSSION

EPSCC accounts for 2.5-5% of all SCC, very rare in male genitourinary tract. Treatment approach is derived from SCLC, guided by extent of disease and patient’s functional status. Role of PCI in EPSCC has not been clearly described, and even less evidence is available for SCCUB. From a review of eleven studies in PubMed for the role of PCI in SCCUB or EPSCC, we found that SCCUB has lower incidence of brain metastases than SCLC. One study suggested that SCCUB arises from totipotent cells in the submucosa, unlike Kulchitsky cell origin of SCLC. This difference might explain the difference in their metastatic behavior. With this background, PCI is not routinely recommended for limited- stage SCCUB. There might still be a role for PCI in extensive SCCUB with high metastatic burden. More studies are needed to update the guidelines for the role of PCI for these tumors.

CONCLUSIONS

Per this literature review, PCI is not routinely recommended for SCCUB, likely due to different cells of origin compared to SCLC. Future studies should focus on characterizing differences in their metastatic behavior and updating guidelines for PCI for SCCUB.

INTRODUCTION

Urinary bladder is an extremely rare site of extrapulmonary small cell cancer (EPSCC). Unlike small cell lung cancer (SCLC), there is no clear guideline for prophylactic cranial irradiation (PCI) for EPSCC. In this case report and literature review, we discuss small cell cancer of urinary bladder (SCCUB) and the role of PCI in SCCUB.

CASE PRESENTATION

A 74-year-old male presented with gross hematuria and an unremarkable physical examination. CT showed 1.7 cm right anterolateral bladder wall thickening. Cystoscopy revealed a 2-3 cm high-grade bladder lesion. Pathology from transurethral resection of the tumor was consistent with T1N0M0 small cell carcinoma. MRI brain and FDG-PET showed no extravesical disease. Patient received four cycles of neoadjuvant carboplatin/etoposide per his preference as he wanted to protect his hearing due to his profession followed by radical cystoprostatectomy. Post-op pathology showed clear margins. We decided to forego PCI in favor of interval surveillance with MRI and follow- up images remain negative for distant metastases.

DISCUSSION

EPSCC accounts for 2.5-5% of all SCC, very rare in male genitourinary tract. Treatment approach is derived from SCLC, guided by extent of disease and patient’s functional status. Role of PCI in EPSCC has not been clearly described, and even less evidence is available for SCCUB. From a review of eleven studies in PubMed for the role of PCI in SCCUB or EPSCC, we found that SCCUB has lower incidence of brain metastases than SCLC. One study suggested that SCCUB arises from totipotent cells in the submucosa, unlike Kulchitsky cell origin of SCLC. This difference might explain the difference in their metastatic behavior. With this background, PCI is not routinely recommended for limited- stage SCCUB. There might still be a role for PCI in extensive SCCUB with high metastatic burden. More studies are needed to update the guidelines for the role of PCI for these tumors.

CONCLUSIONS

Per this literature review, PCI is not routinely recommended for SCCUB, likely due to different cells of origin compared to SCLC. Future studies should focus on characterizing differences in their metastatic behavior and updating guidelines for PCI for SCCUB.

INTRODUCTION

Urinary bladder is an extremely rare site of extrapulmonary small cell cancer (EPSCC). Unlike small cell lung cancer (SCLC), there is no clear guideline for prophylactic cranial irradiation (PCI) for EPSCC. In this case report and literature review, we discuss small cell cancer of urinary bladder (SCCUB) and the role of PCI in SCCUB.

CASE PRESENTATION

A 74-year-old male presented with gross hematuria and an unremarkable physical examination. CT showed 1.7 cm right anterolateral bladder wall thickening. Cystoscopy revealed a 2-3 cm high-grade bladder lesion. Pathology from transurethral resection of the tumor was consistent with T1N0M0 small cell carcinoma. MRI brain and FDG-PET showed no extravesical disease. Patient received four cycles of neoadjuvant carboplatin/etoposide per his preference as he wanted to protect his hearing due to his profession followed by radical cystoprostatectomy. Post-op pathology showed clear margins. We decided to forego PCI in favor of interval surveillance with MRI and follow- up images remain negative for distant metastases.

DISCUSSION

EPSCC accounts for 2.5-5% of all SCC, very rare in male genitourinary tract. Treatment approach is derived from SCLC, guided by extent of disease and patient’s functional status. Role of PCI in EPSCC has not been clearly described, and even less evidence is available for SCCUB. From a review of eleven studies in PubMed for the role of PCI in SCCUB or EPSCC, we found that SCCUB has lower incidence of brain metastases than SCLC. One study suggested that SCCUB arises from totipotent cells in the submucosa, unlike Kulchitsky cell origin of SCLC. This difference might explain the difference in their metastatic behavior. With this background, PCI is not routinely recommended for limited- stage SCCUB. There might still be a role for PCI in extensive SCCUB with high metastatic burden. More studies are needed to update the guidelines for the role of PCI for these tumors.

CONCLUSIONS

Per this literature review, PCI is not routinely recommended for SCCUB, likely due to different cells of origin compared to SCLC. Future studies should focus on characterizing differences in their metastatic behavior and updating guidelines for PCI for SCCUB.

In resectable non–small cell lung cancer (NSCLC), neoadjuvant durvalumab in combination with chemotherapy had no effect on surgical outcomes, according to the most recent analysis of data from the phase 3 AEGEAN study.

“In terms of cancellation of surgery, surgical delay, surgically related adverse events, complications, operation time, and operation procedure, there was no difference between the durvalumab group and the placebo group. In addition, the R0 resection rate was numerically higher in the durvalumab group. These [results] indicate that adding perioperative durvalumab did not adversely affect surgical outcomes,” wrote Tetsuya Mitsudomi, MD, PhD, who presented the new results at the annual World Conference on Lung Cancer, in an email. The topline results of AEGEAN were presented earlier this year at AACR 2023, which showed that the regimen combined with adjuvant durvalumab improved event-free survival (EFS) and pathologic complete response (pCR), compared with chemotherapy plus placebo.

Dr. Mitsudomi also pointed out that AEGEAN is one of the first studies looking at immune checkpoint inhibitors (ICI) in the perioperative settings that demonstrated improved EFS and pCR with no effect on surgical outcomes. Previously, the CheckMate 816 study demonstrated efficacy of neoadjuvant ICI alone.

“The AEGEAN study showed that neoadjuvant plus adjuvant ICI is another option for these patients. However, no one knows who should receive the postoperative ICI in addition to neoadjuvant ICI, because there are no trials including ongoing ones that ask this question,” wrote Dr. Mitsudomi.

The phase 3 AEGEAN study included 740 patients who were randomized to durvalumab or placebo. The median age was 65.0 years in both groups, and 33.3% and 33.4% of patients in each group respectively had fewer than 1% of tumor cells that expressed PD-L1. Expression in 1-49% of tumor cells occurred in 36.9% and 38.0% respectively, and expression ≥ 50% occurred in 29.8% and 28.6%.

Prior to surgery, 84.7% of the durvalumab arm completed four cycles of chemotherapy, as did 87.2% in the placebo arm. The proportion of patients undergoing surgery was 80.6% and 80.7% in the two arms, respectively, and surgical completion was achieved in 77.6% and 76.7%. The durvalumab arm and placebo arm had similar median times from last neoadjuvant treatment to surgery (34.0 days for both) and median time from surgery to first adjuvant dose (50.0 versus 52.0 days).

Among patients with stage II NSCLC, 84.3% in the durvalumab arm underwent surgery, versus 88.9% in the placebo arm. Among patients with stage III disease, the numbers were 79.2% and 77.4%, respectively. There was no surgical delay in 82.7% of patients in the durvalumab arm, compared with 77.8% in the placebo arm. The most common reason for surgical delay was logistical reasons. Mediastinal lymph node dissection was completed in 86.6% of the durvalumab arm and 84.7% of the placebo arm. In both groups where surgery was completed, R0 resection rates were over 90% overall as well as in both stage I and stage II patients. Following surgery, adverse events possibly related to surgery occurred in 40.2% of the durvalumab group and 39.2% of the placebo group. The most common surgical adverse events occurred at similar frequency between groups.

After the presentation, Solange Peters, MD, PhD, served as a discussant. She pointed out other studies that have examined ICI therapy for NSCLC in both the neoadjuvant and adjuvant setting, including Keynote-671 (pembrolizumab), Neotorch (toripalimab), CheckMate 77T (nivolumab), and Impower030 (atezolizumab). She pointed out that AEGEAN, Keynote-671, CheckMate 816, and NeoTorch all had similar trial designs and showed similar magnitude of benefit. “We have a growing paradigm [for combining neoadjuvant and adjuvant ICI therapy]. We are quite all convinced in the community that there is a biological rationale to use neoadjuvant immunotherapy because of the fit immune system, because of the presence of the neoantigens within the tumor at the time of the start of neoadjuvant treatment, [leading to] better priming of immune cells,” said Dr. Peters, who is a professor of medical oncology at University Hospital of Lausanne, Switzerland.

About one in five patients across the trials who would be eligible for surgery never undergo it, but there is promising data from CheckMate 816 that neoadjuvant ICB may improve the odds of surgery, according to Dr. Solange. The AEGEAN data produced some “quite interesting” data about the reasons that patients don’t make it to surgery, as it showed that 8%-10% of patients don’t reach surgery because of progression, but 10%-15% may fall out because they turned out not to be a good candidate for surgery. “I think we probably have to blame the enthusiasm we have to add all these patients into the trial, hoping for the best for the patient but maybe making a wrong selection,” said Dr. Peters.

The study was funded by AstraZeneca. Dr. Mitsudomi has received speaker fees, honoraria, or research funding from AstraZeneca, Chugai, Ono, Bristol Myers Squibb, and MSD. Dr. Peters has financial relationships with AstraZeneca as well as a wide range of other pharmaceutical companies.

In resectable non–small cell lung cancer (NSCLC), neoadjuvant durvalumab in combination with chemotherapy had no effect on surgical outcomes, according to the most recent analysis of data from the phase 3 AEGEAN study.

“In terms of cancellation of surgery, surgical delay, surgically related adverse events, complications, operation time, and operation procedure, there was no difference between the durvalumab group and the placebo group. In addition, the R0 resection rate was numerically higher in the durvalumab group. These [results] indicate that adding perioperative durvalumab did not adversely affect surgical outcomes,” wrote Tetsuya Mitsudomi, MD, PhD, who presented the new results at the annual World Conference on Lung Cancer, in an email. The topline results of AEGEAN were presented earlier this year at AACR 2023, which showed that the regimen combined with adjuvant durvalumab improved event-free survival (EFS) and pathologic complete response (pCR), compared with chemotherapy plus placebo.

Dr. Mitsudomi also pointed out that AEGEAN is one of the first studies looking at immune checkpoint inhibitors (ICI) in the perioperative settings that demonstrated improved EFS and pCR with no effect on surgical outcomes. Previously, the CheckMate 816 study demonstrated efficacy of neoadjuvant ICI alone.

“The AEGEAN study showed that neoadjuvant plus adjuvant ICI is another option for these patients. However, no one knows who should receive the postoperative ICI in addition to neoadjuvant ICI, because there are no trials including ongoing ones that ask this question,” wrote Dr. Mitsudomi.

The phase 3 AEGEAN study included 740 patients who were randomized to durvalumab or placebo. The median age was 65.0 years in both groups, and 33.3% and 33.4% of patients in each group respectively had fewer than 1% of tumor cells that expressed PD-L1. Expression in 1-49% of tumor cells occurred in 36.9% and 38.0% respectively, and expression ≥ 50% occurred in 29.8% and 28.6%.

Prior to surgery, 84.7% of the durvalumab arm completed four cycles of chemotherapy, as did 87.2% in the placebo arm. The proportion of patients undergoing surgery was 80.6% and 80.7% in the two arms, respectively, and surgical completion was achieved in 77.6% and 76.7%. The durvalumab arm and placebo arm had similar median times from last neoadjuvant treatment to surgery (34.0 days for both) and median time from surgery to first adjuvant dose (50.0 versus 52.0 days).

Among patients with stage II NSCLC, 84.3% in the durvalumab arm underwent surgery, versus 88.9% in the placebo arm. Among patients with stage III disease, the numbers were 79.2% and 77.4%, respectively. There was no surgical delay in 82.7% of patients in the durvalumab arm, compared with 77.8% in the placebo arm. The most common reason for surgical delay was logistical reasons. Mediastinal lymph node dissection was completed in 86.6% of the durvalumab arm and 84.7% of the placebo arm. In both groups where surgery was completed, R0 resection rates were over 90% overall as well as in both stage I and stage II patients. Following surgery, adverse events possibly related to surgery occurred in 40.2% of the durvalumab group and 39.2% of the placebo group. The most common surgical adverse events occurred at similar frequency between groups.

After the presentation, Solange Peters, MD, PhD, served as a discussant. She pointed out other studies that have examined ICI therapy for NSCLC in both the neoadjuvant and adjuvant setting, including Keynote-671 (pembrolizumab), Neotorch (toripalimab), CheckMate 77T (nivolumab), and Impower030 (atezolizumab). She pointed out that AEGEAN, Keynote-671, CheckMate 816, and NeoTorch all had similar trial designs and showed similar magnitude of benefit. “We have a growing paradigm [for combining neoadjuvant and adjuvant ICI therapy]. We are quite all convinced in the community that there is a biological rationale to use neoadjuvant immunotherapy because of the fit immune system, because of the presence of the neoantigens within the tumor at the time of the start of neoadjuvant treatment, [leading to] better priming of immune cells,” said Dr. Peters, who is a professor of medical oncology at University Hospital of Lausanne, Switzerland.

About one in five patients across the trials who would be eligible for surgery never undergo it, but there is promising data from CheckMate 816 that neoadjuvant ICB may improve the odds of surgery, according to Dr. Solange. The AEGEAN data produced some “quite interesting” data about the reasons that patients don’t make it to surgery, as it showed that 8%-10% of patients don’t reach surgery because of progression, but 10%-15% may fall out because they turned out not to be a good candidate for surgery. “I think we probably have to blame the enthusiasm we have to add all these patients into the trial, hoping for the best for the patient but maybe making a wrong selection,” said Dr. Peters.

The study was funded by AstraZeneca. Dr. Mitsudomi has received speaker fees, honoraria, or research funding from AstraZeneca, Chugai, Ono, Bristol Myers Squibb, and MSD. Dr. Peters has financial relationships with AstraZeneca as well as a wide range of other pharmaceutical companies.

In resectable non–small cell lung cancer (NSCLC), neoadjuvant durvalumab in combination with chemotherapy had no effect on surgical outcomes, according to the most recent analysis of data from the phase 3 AEGEAN study.

“In terms of cancellation of surgery, surgical delay, surgically related adverse events, complications, operation time, and operation procedure, there was no difference between the durvalumab group and the placebo group. In addition, the R0 resection rate was numerically higher in the durvalumab group. These [results] indicate that adding perioperative durvalumab did not adversely affect surgical outcomes,” wrote Tetsuya Mitsudomi, MD, PhD, who presented the new results at the annual World Conference on Lung Cancer, in an email. The topline results of AEGEAN were presented earlier this year at AACR 2023, which showed that the regimen combined with adjuvant durvalumab improved event-free survival (EFS) and pathologic complete response (pCR), compared with chemotherapy plus placebo.

Dr. Mitsudomi also pointed out that AEGEAN is one of the first studies looking at immune checkpoint inhibitors (ICI) in the perioperative settings that demonstrated improved EFS and pCR with no effect on surgical outcomes. Previously, the CheckMate 816 study demonstrated efficacy of neoadjuvant ICI alone.

“The AEGEAN study showed that neoadjuvant plus adjuvant ICI is another option for these patients. However, no one knows who should receive the postoperative ICI in addition to neoadjuvant ICI, because there are no trials including ongoing ones that ask this question,” wrote Dr. Mitsudomi.

The phase 3 AEGEAN study included 740 patients who were randomized to durvalumab or placebo. The median age was 65.0 years in both groups, and 33.3% and 33.4% of patients in each group respectively had fewer than 1% of tumor cells that expressed PD-L1. Expression in 1-49% of tumor cells occurred in 36.9% and 38.0% respectively, and expression ≥ 50% occurred in 29.8% and 28.6%.

Prior to surgery, 84.7% of the durvalumab arm completed four cycles of chemotherapy, as did 87.2% in the placebo arm. The proportion of patients undergoing surgery was 80.6% and 80.7% in the two arms, respectively, and surgical completion was achieved in 77.6% and 76.7%. The durvalumab arm and placebo arm had similar median times from last neoadjuvant treatment to surgery (34.0 days for both) and median time from surgery to first adjuvant dose (50.0 versus 52.0 days).

Among patients with stage II NSCLC, 84.3% in the durvalumab arm underwent surgery, versus 88.9% in the placebo arm. Among patients with stage III disease, the numbers were 79.2% and 77.4%, respectively. There was no surgical delay in 82.7% of patients in the durvalumab arm, compared with 77.8% in the placebo arm. The most common reason for surgical delay was logistical reasons. Mediastinal lymph node dissection was completed in 86.6% of the durvalumab arm and 84.7% of the placebo arm. In both groups where surgery was completed, R0 resection rates were over 90% overall as well as in both stage I and stage II patients. Following surgery, adverse events possibly related to surgery occurred in 40.2% of the durvalumab group and 39.2% of the placebo group. The most common surgical adverse events occurred at similar frequency between groups.

After the presentation, Solange Peters, MD, PhD, served as a discussant. She pointed out other studies that have examined ICI therapy for NSCLC in both the neoadjuvant and adjuvant setting, including Keynote-671 (pembrolizumab), Neotorch (toripalimab), CheckMate 77T (nivolumab), and Impower030 (atezolizumab). She pointed out that AEGEAN, Keynote-671, CheckMate 816, and NeoTorch all had similar trial designs and showed similar magnitude of benefit. “We have a growing paradigm [for combining neoadjuvant and adjuvant ICI therapy]. We are quite all convinced in the community that there is a biological rationale to use neoadjuvant immunotherapy because of the fit immune system, because of the presence of the neoantigens within the tumor at the time of the start of neoadjuvant treatment, [leading to] better priming of immune cells,” said Dr. Peters, who is a professor of medical oncology at University Hospital of Lausanne, Switzerland.

About one in five patients across the trials who would be eligible for surgery never undergo it, but there is promising data from CheckMate 816 that neoadjuvant ICB may improve the odds of surgery, according to Dr. Solange. The AEGEAN data produced some “quite interesting” data about the reasons that patients don’t make it to surgery, as it showed that 8%-10% of patients don’t reach surgery because of progression, but 10%-15% may fall out because they turned out not to be a good candidate for surgery. “I think we probably have to blame the enthusiasm we have to add all these patients into the trial, hoping for the best for the patient but maybe making a wrong selection,” said Dr. Peters.

The study was funded by AstraZeneca. Dr. Mitsudomi has received speaker fees, honoraria, or research funding from AstraZeneca, Chugai, Ono, Bristol Myers Squibb, and MSD. Dr. Peters has financial relationships with AstraZeneca as well as a wide range of other pharmaceutical companies.

A debate in Houston at the annual meeting of the Society of Hematologic Oncology tackled a vexing issue in hematology: Should smoldering myeloma be treated?

Hematologist Sagar Lonial, MD, a multiple myeloma specialist and researcher at Emory University, Atlanta, argued for treatment. Hematologist Angela Dispenzieri, MD, also a myeloma researcher and specialist at the Mayo Clinic in Rochester, Minn., took the opposing side, arguing for watchful waiting.

The two experts based their arguments largely on the same two studies, the only randomized trials to tackle the issue to date. While Dr. Dispenzieri focused on their shortcomings, Dr. Lonial focused on their strengths.

In a poll after the debate, about a third of audience members agreed that watchful waiting is the way to go, but about two-thirds favored a personalized approach to smoldering myeloma treatment based on patient risk.

“I’m taking this as a win,” Dr. Lonial said.

Different interpretations of two trials

The first of the two trials recruited from 2007 to 2010 and was conducted in Spain and Portugal. Fifty-seven high-risk patients were randomized to lenalidomide plus dexamethasone (Len-Dex) for up to 2 years; 62 others were randomized to observation.

At 3 years, 70% of observed patients had progressed to multiple myeloma versus only 20% in the Len-Dex group; 82% of Len-Dex patients were alive at data cut-off in 2015 versus 64% of observation patients.

The second, more recent trial, which was led by Dr. Lonial, randomized 92 intermediate or high-risk smoldering myeloma patients to lenalidomide alone for a median of 2 years and 90 others to observation. Three-year progression-free survival (PFS) was 91% in the treatment arm versus 66% with observation. Overall survival data have not yet been reported.

Dr. Dispenzieri acknowledged that the results from Spain and Portugal are impressive. “Treating with Len-Dex gives you a far superior freedom from progression. ... Overall survival was better too.” Results for Len-Dex were “fantastic,” she said.

However, the trial was done before myeloma-defining event criteria existed, so it’s very likely that the treatment arm in the Spanish study included actual myeloma cases, she said.

About 46% of treated patients in Dr. Lonial’s study met the current definition for high risk for progression based on the 2-20-20 rule, which Dr. Dispenzieri helped develop. Although there was an improvement in PFS in the high-risk group, there was no significant improvement for intermediate- and low-risk subjects. Also, more than 80% of observed patients hadn’t progressed by 2 years, and overall survival data are missing.

Meanwhile, treated patients in both trials had more adverse events, including secondary malignancies, and there’s the possibility that early treatment may make patients resistant to treatment later on when they progress to multiple myeloma, although that didn’t seem to happen in the Spanish trial.

“Of course, we want to prevent morbidity, of course we would love to cure the disease,” but “should we treat high-risk smoldering myeloma patients based on overall survival data from a trial of” just 119 “patients that may have been contaminated with actual myeloma” cases? Is it ethical to treat low- and intermediate-risk patients who have only a 50% chance of developing myeloma after 10 years?”

Her answer to both questions was “no and no. ... There’s just a lot of work to be done” to better understand the condition and when and how to intervene. In the meantime, “don’t treat smoldering melanoma patients” outside of a trial, she said.

“First, do no harm,” Dr. Dispenzieri cautioned in her final slide.

Dr. Lonial said he agreed with many of Dr. Dispenzieri’s points, but disagreed with her conclusion not to treat.

“Everybody can always be critical of randomized trials, but at the end of the day, we now have two randomized phase 3 trials comparing early intervention with no intervention demonstrating a significant delay in developing myeloma. I think it’s time to end the ‘we need more data; we need more trials.’ It’s time for us to take a stand.”

He argued for 2 years of lenalidomide for patients who meet the 2-20-20 high-risk definition, based on the median time people were treated in his trial.

He said he discusses the option “with every smoldering patient [who] walks in to see me” if they aren’t eligible for a trial.

Dr. Lonial mentioned his team is currently pulling together longer-term survival data for their trial.

A debate in Houston at the annual meeting of the Society of Hematologic Oncology tackled a vexing issue in hematology: Should smoldering myeloma be treated?

Hematologist Sagar Lonial, MD, a multiple myeloma specialist and researcher at Emory University, Atlanta, argued for treatment. Hematologist Angela Dispenzieri, MD, also a myeloma researcher and specialist at the Mayo Clinic in Rochester, Minn., took the opposing side, arguing for watchful waiting.

The two experts based their arguments largely on the same two studies, the only randomized trials to tackle the issue to date. While Dr. Dispenzieri focused on their shortcomings, Dr. Lonial focused on their strengths.

In a poll after the debate, about a third of audience members agreed that watchful waiting is the way to go, but about two-thirds favored a personalized approach to smoldering myeloma treatment based on patient risk.

“I’m taking this as a win,” Dr. Lonial said.

Different interpretations of two trials

The first of the two trials recruited from 2007 to 2010 and was conducted in Spain and Portugal. Fifty-seven high-risk patients were randomized to lenalidomide plus dexamethasone (Len-Dex) for up to 2 years; 62 others were randomized to observation.

At 3 years, 70% of observed patients had progressed to multiple myeloma versus only 20% in the Len-Dex group; 82% of Len-Dex patients were alive at data cut-off in 2015 versus 64% of observation patients.

The second, more recent trial, which was led by Dr. Lonial, randomized 92 intermediate or high-risk smoldering myeloma patients to lenalidomide alone for a median of 2 years and 90 others to observation. Three-year progression-free survival (PFS) was 91% in the treatment arm versus 66% with observation. Overall survival data have not yet been reported.

Dr. Dispenzieri acknowledged that the results from Spain and Portugal are impressive. “Treating with Len-Dex gives you a far superior freedom from progression. ... Overall survival was better too.” Results for Len-Dex were “fantastic,” she said.

However, the trial was done before myeloma-defining event criteria existed, so it’s very likely that the treatment arm in the Spanish study included actual myeloma cases, she said.

About 46% of treated patients in Dr. Lonial’s study met the current definition for high risk for progression based on the 2-20-20 rule, which Dr. Dispenzieri helped develop. Although there was an improvement in PFS in the high-risk group, there was no significant improvement for intermediate- and low-risk subjects. Also, more than 80% of observed patients hadn’t progressed by 2 years, and overall survival data are missing.

Meanwhile, treated patients in both trials had more adverse events, including secondary malignancies, and there’s the possibility that early treatment may make patients resistant to treatment later on when they progress to multiple myeloma, although that didn’t seem to happen in the Spanish trial.

“Of course, we want to prevent morbidity, of course we would love to cure the disease,” but “should we treat high-risk smoldering myeloma patients based on overall survival data from a trial of” just 119 “patients that may have been contaminated with actual myeloma” cases? Is it ethical to treat low- and intermediate-risk patients who have only a 50% chance of developing myeloma after 10 years?”

Her answer to both questions was “no and no. ... There’s just a lot of work to be done” to better understand the condition and when and how to intervene. In the meantime, “don’t treat smoldering melanoma patients” outside of a trial, she said.

“First, do no harm,” Dr. Dispenzieri cautioned in her final slide.

Dr. Lonial said he agreed with many of Dr. Dispenzieri’s points, but disagreed with her conclusion not to treat.

“Everybody can always be critical of randomized trials, but at the end of the day, we now have two randomized phase 3 trials comparing early intervention with no intervention demonstrating a significant delay in developing myeloma. I think it’s time to end the ‘we need more data; we need more trials.’ It’s time for us to take a stand.”

He argued for 2 years of lenalidomide for patients who meet the 2-20-20 high-risk definition, based on the median time people were treated in his trial.

He said he discusses the option “with every smoldering patient [who] walks in to see me” if they aren’t eligible for a trial.

Dr. Lonial mentioned his team is currently pulling together longer-term survival data for their trial.

A debate in Houston at the annual meeting of the Society of Hematologic Oncology tackled a vexing issue in hematology: Should smoldering myeloma be treated?

Hematologist Sagar Lonial, MD, a multiple myeloma specialist and researcher at Emory University, Atlanta, argued for treatment. Hematologist Angela Dispenzieri, MD, also a myeloma researcher and specialist at the Mayo Clinic in Rochester, Minn., took the opposing side, arguing for watchful waiting.

The two experts based their arguments largely on the same two studies, the only randomized trials to tackle the issue to date. While Dr. Dispenzieri focused on their shortcomings, Dr. Lonial focused on their strengths.

In a poll after the debate, about a third of audience members agreed that watchful waiting is the way to go, but about two-thirds favored a personalized approach to smoldering myeloma treatment based on patient risk.

“I’m taking this as a win,” Dr. Lonial said.

Different interpretations of two trials

The first of the two trials recruited from 2007 to 2010 and was conducted in Spain and Portugal. Fifty-seven high-risk patients were randomized to lenalidomide plus dexamethasone (Len-Dex) for up to 2 years; 62 others were randomized to observation.

At 3 years, 70% of observed patients had progressed to multiple myeloma versus only 20% in the Len-Dex group; 82% of Len-Dex patients were alive at data cut-off in 2015 versus 64% of observation patients.

The second, more recent trial, which was led by Dr. Lonial, randomized 92 intermediate or high-risk smoldering myeloma patients to lenalidomide alone for a median of 2 years and 90 others to observation. Three-year progression-free survival (PFS) was 91% in the treatment arm versus 66% with observation. Overall survival data have not yet been reported.

Dr. Dispenzieri acknowledged that the results from Spain and Portugal are impressive. “Treating with Len-Dex gives you a far superior freedom from progression. ... Overall survival was better too.” Results for Len-Dex were “fantastic,” she said.

However, the trial was done before myeloma-defining event criteria existed, so it’s very likely that the treatment arm in the Spanish study included actual myeloma cases, she said.

About 46% of treated patients in Dr. Lonial’s study met the current definition for high risk for progression based on the 2-20-20 rule, which Dr. Dispenzieri helped develop. Although there was an improvement in PFS in the high-risk group, there was no significant improvement for intermediate- and low-risk subjects. Also, more than 80% of observed patients hadn’t progressed by 2 years, and overall survival data are missing.

Meanwhile, treated patients in both trials had more adverse events, including secondary malignancies, and there’s the possibility that early treatment may make patients resistant to treatment later on when they progress to multiple myeloma, although that didn’t seem to happen in the Spanish trial.

“Of course, we want to prevent morbidity, of course we would love to cure the disease,” but “should we treat high-risk smoldering myeloma patients based on overall survival data from a trial of” just 119 “patients that may have been contaminated with actual myeloma” cases? Is it ethical to treat low- and intermediate-risk patients who have only a 50% chance of developing myeloma after 10 years?”

Her answer to both questions was “no and no. ... There’s just a lot of work to be done” to better understand the condition and when and how to intervene. In the meantime, “don’t treat smoldering melanoma patients” outside of a trial, she said.

“First, do no harm,” Dr. Dispenzieri cautioned in her final slide.

Dr. Lonial said he agreed with many of Dr. Dispenzieri’s points, but disagreed with her conclusion not to treat.

“Everybody can always be critical of randomized trials, but at the end of the day, we now have two randomized phase 3 trials comparing early intervention with no intervention demonstrating a significant delay in developing myeloma. I think it’s time to end the ‘we need more data; we need more trials.’ It’s time for us to take a stand.”

He argued for 2 years of lenalidomide for patients who meet the 2-20-20 high-risk definition, based on the median time people were treated in his trial.

He said he discusses the option “with every smoldering patient [who] walks in to see me” if they aren’t eligible for a trial.

Dr. Lonial mentioned his team is currently pulling together longer-term survival data for their trial.

Adding platinum-based chemotherapy to osimertinib (Tagrisso) in the first-line treatment of EGFR-mutated advanced non–small cell lung cancer (NSCLC) improved progression-free survival (PFS), according to interim results from the FLAURA2 trial.

Combining the third-generation tyrosine kinase inhibitor (TKI) with platinum-based chemotherapy achieved “statistically significant and clinically meaningful improvement in PFS over osimertinib monotherapy,” said Pasi A. Jänne, MD, PhD, professor of medicine at Harvard Medical School and director of the Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, both in Boston, who presented the interim findings at the annual World Conference on Lung Cancer.

However, experts raised some questions about whether the combination would also offer improved overall survival and whether the accompanying toxicity would be acceptable to patients.

Yi-Long Wu, MD, PhD, who was not involved in the research, said that although the combination regimen does appear to offer a benefit, it may come at a steep cost.

Patients who received the combination had an almost fourfold greater risk of grade 3 or higher adverse events related to treatment, said Dr. Wu, professor of oncology, Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital, Guangzhou, China.

And, notably, because the overall survival data in the interim analysis are immature, it’s unclear whether the combination will offer an overall survival benefit over osimertinib monotherapy, Dr. Wu said.

The 2019 FLAURA trial, which compared TKI monotherapy, demonstrated an overall survival advantage among patients who received osimertinib vs. a first-generation EGFR TKI, such as gefitinib (Iressa) or erlotinib (Tarceva). These data established the third-generation TKI as the preferred first-line treatment for patients with advanced EGFR NSCLC.

But resistance to EGFR TKIs remains a problem, which has led experts to explore combination strategies that might overcome resistance and improve clinical outcomes. Recent data indicate that combining first-generation EGFR TKIs with chemotherapy may have an additive effect and further improve outcomes with the drugs. And a recent study of untreated EGFR-mutated advanced NSCLC found patients receiving osimertinib plus platinum-pemetrexed demonstrated a promising objective response rate; however, Dr. Jänne noted that the combination has not been tested in a randomized trial.

To better understand the potential additive benefit of osimertinib and chemotherapy, the team conduced a global, open-label study in patients with pathologically confirmed nonsquamous NSCLC who had received no prior systemic therapy for advanced NSCLC and had a performance status of 0 or 1.

The team randomly assigned 557 patients to daily osimertinib alone or osimertinib plus chemotherapy with pemetrexed and carboplatin or cisplatin every 3 weeks for four cycles, followed by maintenance osimertinib plus pemetrexed every 3 weeks.

Treatment was continued until radiological disease progression, as defined using the RECIST 1.1 criteria, or other withdrawal criteria were met. The patients were assessed at weeks 6 and 12, and again every 12 weeks.

The median age of the patients was about 61 years, approximately 61% were female, and about 25% were Asian. Around two-thirds were never-smokers, about 60% had either Ex19del or L858R EGFR mutations, and about 40% had central nervous system metastases.

At the data cutoff, the median follow-up was 16.5 months in the osimertinib monotherapy arm and 19.5 months in the combination arm. Overall, 45% of patients on monotherapy and 56% in the combination arm were still on treatment.

Dr. Jänne reported that osimertinib plus chemotherapy was associated with a greater objective response rate than monotherapy – 83.2% vs. 75.5% – and a longer median duration of response – 24 months vs. 15.3 months.

Patients receiving the combination showed significant improvements in PFS – 25.5 months vs. 16.7 months (hazard ratio, 0.62; P < .0001). At 24 months, 57% of the patients in the combination arm were disease-free vs. 41% in the monotherapy group.

The benefit held across all patient subgroups, including age, sex, smoking history, and EGFR mutation type at baseline.

The PFS benefit appeared most pronounced among patients with CNS metastases at baseline – a median of 24.9 months in the combination arm vs. 13.8 months with monotherapy (HR, 0.47). But patients without CNS metastases who received the combination therapy also showed improvements in PFS (HR, 0.75).

Should there be an overall survival improvement, then the regimen used in FLAURA2 could become the “new standard of care in EGFR-mutated NSCLC in the first-line setting,” particularly in patients with CNS metastases and/or an exon21 mutation, Dr. Wu said. If, however, further analysis indicates no overall survival benefit, then patients will have experienced chemotherapy side effects earlier and longer than those receiving monotherapy, with no life gain.

Dr. Wu pointed out that the future role and sequence of the combination will also hinge on understanding how patients become resistant to it as well as whether the toxicity is manageable.

The FLAURA2 safety data indicated that the combination led to higher rates of grade 3 or higher adverse events overall – 64% vs. 27% – and higher rates of grade 3 or higher adverse events possibly related to treatment – 53% vs. 11%.

Experts who commented on the study findings via X (formerly Twitter) echoed Dr. Wu’s sentiments about the study findings and implications.

Mohana Roy, MD, said she did not find the results surprising, given that “many of us are adding chemo on slow progression on osimertinib already,” but noted that “questions of sequencing” remain.

Christian Rolfo, MD, PhD, MBA, commented that questions about the “real benefit” of osimertinib plus chemotherapy in subgroups and degree of resistance remain. Further toxicity and overall survival data “will clarify the future of the combination,” said Dr. Rolfo, of Icahn School of Medicine at Mount Sinai, New York.

The study was funded by AstraZeneca. Dr. Jänne declared relationships with Gatekeeper Pharmaceuticals, Labcorp, Astellas Pharmaceuticals, AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, PUMA, Revolution Medicines, Takeda Oncology, Biocartis, Mirati Therapeutics, Transcenta, ACEA Biosciences, Araxes, Bayer, Chugai Pharmaceuticals, Eisai, Ignyta, Novartis, Nuvalent, Pfizer, Roche/Genentech, Sanofi, SFJ Pharmaceuticals, Silicon Therapeutics, Syndax, and Voronoi.

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

Adding platinum-based chemotherapy to osimertinib (Tagrisso) in the first-line treatment of EGFR-mutated advanced non–small cell lung cancer (NSCLC) improved progression-free survival (PFS), according to interim results from the FLAURA2 trial.

Combining the third-generation tyrosine kinase inhibitor (TKI) with platinum-based chemotherapy achieved “statistically significant and clinically meaningful improvement in PFS over osimertinib monotherapy,” said Pasi A. Jänne, MD, PhD, professor of medicine at Harvard Medical School and director of the Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, both in Boston, who presented the interim findings at the annual World Conference on Lung Cancer.

However, experts raised some questions about whether the combination would also offer improved overall survival and whether the accompanying toxicity would be acceptable to patients.

Yi-Long Wu, MD, PhD, who was not involved in the research, said that although the combination regimen does appear to offer a benefit, it may come at a steep cost.

Patients who received the combination had an almost fourfold greater risk of grade 3 or higher adverse events related to treatment, said Dr. Wu, professor of oncology, Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital, Guangzhou, China.

And, notably, because the overall survival data in the interim analysis are immature, it’s unclear whether the combination will offer an overall survival benefit over osimertinib monotherapy, Dr. Wu said.

The 2019 FLAURA trial, which compared TKI monotherapy, demonstrated an overall survival advantage among patients who received osimertinib vs. a first-generation EGFR TKI, such as gefitinib (Iressa) or erlotinib (Tarceva). These data established the third-generation TKI as the preferred first-line treatment for patients with advanced EGFR NSCLC.

But resistance to EGFR TKIs remains a problem, which has led experts to explore combination strategies that might overcome resistance and improve clinical outcomes. Recent data indicate that combining first-generation EGFR TKIs with chemotherapy may have an additive effect and further improve outcomes with the drugs. And a recent study of untreated EGFR-mutated advanced NSCLC found patients receiving osimertinib plus platinum-pemetrexed demonstrated a promising objective response rate; however, Dr. Jänne noted that the combination has not been tested in a randomized trial.

To better understand the potential additive benefit of osimertinib and chemotherapy, the team conduced a global, open-label study in patients with pathologically confirmed nonsquamous NSCLC who had received no prior systemic therapy for advanced NSCLC and had a performance status of 0 or 1.

The team randomly assigned 557 patients to daily osimertinib alone or osimertinib plus chemotherapy with pemetrexed and carboplatin or cisplatin every 3 weeks for four cycles, followed by maintenance osimertinib plus pemetrexed every 3 weeks.

Treatment was continued until radiological disease progression, as defined using the RECIST 1.1 criteria, or other withdrawal criteria were met. The patients were assessed at weeks 6 and 12, and again every 12 weeks.

The median age of the patients was about 61 years, approximately 61% were female, and about 25% were Asian. Around two-thirds were never-smokers, about 60% had either Ex19del or L858R EGFR mutations, and about 40% had central nervous system metastases.

At the data cutoff, the median follow-up was 16.5 months in the osimertinib monotherapy arm and 19.5 months in the combination arm. Overall, 45% of patients on monotherapy and 56% in the combination arm were still on treatment.

Dr. Jänne reported that osimertinib plus chemotherapy was associated with a greater objective response rate than monotherapy – 83.2% vs. 75.5% – and a longer median duration of response – 24 months vs. 15.3 months.

Patients receiving the combination showed significant improvements in PFS – 25.5 months vs. 16.7 months (hazard ratio, 0.62; P < .0001). At 24 months, 57% of the patients in the combination arm were disease-free vs. 41% in the monotherapy group.

The benefit held across all patient subgroups, including age, sex, smoking history, and EGFR mutation type at baseline.

The PFS benefit appeared most pronounced among patients with CNS metastases at baseline – a median of 24.9 months in the combination arm vs. 13.8 months with monotherapy (HR, 0.47). But patients without CNS metastases who received the combination therapy also showed improvements in PFS (HR, 0.75).

Should there be an overall survival improvement, then the regimen used in FLAURA2 could become the “new standard of care in EGFR-mutated NSCLC in the first-line setting,” particularly in patients with CNS metastases and/or an exon21 mutation, Dr. Wu said. If, however, further analysis indicates no overall survival benefit, then patients will have experienced chemotherapy side effects earlier and longer than those receiving monotherapy, with no life gain.

Dr. Wu pointed out that the future role and sequence of the combination will also hinge on understanding how patients become resistant to it as well as whether the toxicity is manageable.

The FLAURA2 safety data indicated that the combination led to higher rates of grade 3 or higher adverse events overall – 64% vs. 27% – and higher rates of grade 3 or higher adverse events possibly related to treatment – 53% vs. 11%.

Experts who commented on the study findings via X (formerly Twitter) echoed Dr. Wu’s sentiments about the study findings and implications.

Mohana Roy, MD, said she did not find the results surprising, given that “many of us are adding chemo on slow progression on osimertinib already,” but noted that “questions of sequencing” remain.

Christian Rolfo, MD, PhD, MBA, commented that questions about the “real benefit” of osimertinib plus chemotherapy in subgroups and degree of resistance remain. Further toxicity and overall survival data “will clarify the future of the combination,” said Dr. Rolfo, of Icahn School of Medicine at Mount Sinai, New York.

The study was funded by AstraZeneca. Dr. Jänne declared relationships with Gatekeeper Pharmaceuticals, Labcorp, Astellas Pharmaceuticals, AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, PUMA, Revolution Medicines, Takeda Oncology, Biocartis, Mirati Therapeutics, Transcenta, ACEA Biosciences, Araxes, Bayer, Chugai Pharmaceuticals, Eisai, Ignyta, Novartis, Nuvalent, Pfizer, Roche/Genentech, Sanofi, SFJ Pharmaceuticals, Silicon Therapeutics, Syndax, and Voronoi.

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

Adding platinum-based chemotherapy to osimertinib (Tagrisso) in the first-line treatment of EGFR-mutated advanced non–small cell lung cancer (NSCLC) improved progression-free survival (PFS), according to interim results from the FLAURA2 trial.

Combining the third-generation tyrosine kinase inhibitor (TKI) with platinum-based chemotherapy achieved “statistically significant and clinically meaningful improvement in PFS over osimertinib monotherapy,” said Pasi A. Jänne, MD, PhD, professor of medicine at Harvard Medical School and director of the Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, both in Boston, who presented the interim findings at the annual World Conference on Lung Cancer.

However, experts raised some questions about whether the combination would also offer improved overall survival and whether the accompanying toxicity would be acceptable to patients.

Yi-Long Wu, MD, PhD, who was not involved in the research, said that although the combination regimen does appear to offer a benefit, it may come at a steep cost.

Patients who received the combination had an almost fourfold greater risk of grade 3 or higher adverse events related to treatment, said Dr. Wu, professor of oncology, Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital, Guangzhou, China.

And, notably, because the overall survival data in the interim analysis are immature, it’s unclear whether the combination will offer an overall survival benefit over osimertinib monotherapy, Dr. Wu said.

The 2019 FLAURA trial, which compared TKI monotherapy, demonstrated an overall survival advantage among patients who received osimertinib vs. a first-generation EGFR TKI, such as gefitinib (Iressa) or erlotinib (Tarceva). These data established the third-generation TKI as the preferred first-line treatment for patients with advanced EGFR NSCLC.

But resistance to EGFR TKIs remains a problem, which has led experts to explore combination strategies that might overcome resistance and improve clinical outcomes. Recent data indicate that combining first-generation EGFR TKIs with chemotherapy may have an additive effect and further improve outcomes with the drugs. And a recent study of untreated EGFR-mutated advanced NSCLC found patients receiving osimertinib plus platinum-pemetrexed demonstrated a promising objective response rate; however, Dr. Jänne noted that the combination has not been tested in a randomized trial.

To better understand the potential additive benefit of osimertinib and chemotherapy, the team conduced a global, open-label study in patients with pathologically confirmed nonsquamous NSCLC who had received no prior systemic therapy for advanced NSCLC and had a performance status of 0 or 1.

The team randomly assigned 557 patients to daily osimertinib alone or osimertinib plus chemotherapy with pemetrexed and carboplatin or cisplatin every 3 weeks for four cycles, followed by maintenance osimertinib plus pemetrexed every 3 weeks.

Treatment was continued until radiological disease progression, as defined using the RECIST 1.1 criteria, or other withdrawal criteria were met. The patients were assessed at weeks 6 and 12, and again every 12 weeks.

The median age of the patients was about 61 years, approximately 61% were female, and about 25% were Asian. Around two-thirds were never-smokers, about 60% had either Ex19del or L858R EGFR mutations, and about 40% had central nervous system metastases.

At the data cutoff, the median follow-up was 16.5 months in the osimertinib monotherapy arm and 19.5 months in the combination arm. Overall, 45% of patients on monotherapy and 56% in the combination arm were still on treatment.

Dr. Jänne reported that osimertinib plus chemotherapy was associated with a greater objective response rate than monotherapy – 83.2% vs. 75.5% – and a longer median duration of response – 24 months vs. 15.3 months.

Patients receiving the combination showed significant improvements in PFS – 25.5 months vs. 16.7 months (hazard ratio, 0.62; P < .0001). At 24 months, 57% of the patients in the combination arm were disease-free vs. 41% in the monotherapy group.

The benefit held across all patient subgroups, including age, sex, smoking history, and EGFR mutation type at baseline.

The PFS benefit appeared most pronounced among patients with CNS metastases at baseline – a median of 24.9 months in the combination arm vs. 13.8 months with monotherapy (HR, 0.47). But patients without CNS metastases who received the combination therapy also showed improvements in PFS (HR, 0.75).

Should there be an overall survival improvement, then the regimen used in FLAURA2 could become the “new standard of care in EGFR-mutated NSCLC in the first-line setting,” particularly in patients with CNS metastases and/or an exon21 mutation, Dr. Wu said. If, however, further analysis indicates no overall survival benefit, then patients will have experienced chemotherapy side effects earlier and longer than those receiving monotherapy, with no life gain.

Dr. Wu pointed out that the future role and sequence of the combination will also hinge on understanding how patients become resistant to it as well as whether the toxicity is manageable.

The FLAURA2 safety data indicated that the combination led to higher rates of grade 3 or higher adverse events overall – 64% vs. 27% – and higher rates of grade 3 or higher adverse events possibly related to treatment – 53% vs. 11%.

Experts who commented on the study findings via X (formerly Twitter) echoed Dr. Wu’s sentiments about the study findings and implications.

Mohana Roy, MD, said she did not find the results surprising, given that “many of us are adding chemo on slow progression on osimertinib already,” but noted that “questions of sequencing” remain.

Christian Rolfo, MD, PhD, MBA, commented that questions about the “real benefit” of osimertinib plus chemotherapy in subgroups and degree of resistance remain. Further toxicity and overall survival data “will clarify the future of the combination,” said Dr. Rolfo, of Icahn School of Medicine at Mount Sinai, New York.

The study was funded by AstraZeneca. Dr. Jänne declared relationships with Gatekeeper Pharmaceuticals, Labcorp, Astellas Pharmaceuticals, AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, PUMA, Revolution Medicines, Takeda Oncology, Biocartis, Mirati Therapeutics, Transcenta, ACEA Biosciences, Araxes, Bayer, Chugai Pharmaceuticals, Eisai, Ignyta, Novartis, Nuvalent, Pfizer, Roche/Genentech, Sanofi, SFJ Pharmaceuticals, Silicon Therapeutics, Syndax, and Voronoi.

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

INTRODUCTION

Lymphadenopathy in Chronic Lymphocytic Leukemia (CLL) is a very common feature. However, sudden increase in lymphadenopathy or other symptoms like weight loss should be evaluated for possible metastatic malignancy. We describe a CLL patient with diffuse mediastinal lymphadenopathy who was diagnosed with metastatic bladder cancer without a primary bladder tumor mass on imaging.

CASE DESCRIPTION

A 60-year-old man with a 60 pack-year smoking history, alcoholic cirrhosis, and a 5-year history of stage 1 CLL presented with 3 months of progressive shortness of breath; persistent cough; chills; hemoptysis; and a steady weight loss of 35 lbs. Notably, he had no bladder symptoms. Initial labs showed leukocytosis of 35.8k with a lymphocytic predominance. Screening low-dose chest CT was positive for diffuse mediastinal lymphadenopathy. Subsequent PET/CT revealed numerous hypermetabolic lymph nodes in the neck, mediastinum, left hilum, and right periaortic abdominal region. CT Chest, Abdomen, Pelvis revealed progressive lymphadenopathy as seen in prior imaging, stable pulmonary nodules up to 4 mm in size, and splenomegaly. No distant primary sites, including of the bladder, were identified. Mediastinal lymph node biopsy confirmed metastatic poorly differentiated carcinoma with immunohistochemical staining negative for p40, p63, CK20, TTF-1, Napsin A, CDX2, CA19- 9, Calretinin, and D2-40 and positive for CK7, GATA3, Ber-EP4, and Uroplakin, supporting bladder as primary origin. Urology deferred a cystoscopy given his lack of urinary symptoms and positive biopsy and was started on Carboplatin/Gemcitabine for his metastatic disease. He was ineligible for Cisplatin given his cirrhosis and hearing impairment.

DISCUSSION

In patients with CLL, new onset mediastinal lymphadenopathy is concerning for disease progression and possible transformation to a diffuse b-cell lymphoma. However, this symptom has a broad differential, including primary lung carcinomas, sarcomas, and metastatic disease. While our patient’s PET/CT and pan-CT failed to identify a distant primary site, maintaining a low clinical suspicion for metastatic disease and doing a thorough work-up was paramount. Only through immunohistochemical staining were we able to diagnosis this patient with urothelial carcinoma.

CONCLUSIONS

Biopsy with immunohistochemical staining and maintaining a low suspicion for worsening lymphadenopathy can identify unusually presenting urothelial carcinomas in CLL patients.

INTRODUCTION

Lymphadenopathy in Chronic Lymphocytic Leukemia (CLL) is a very common feature. However, sudden increase in lymphadenopathy or other symptoms like weight loss should be evaluated for possible metastatic malignancy. We describe a CLL patient with diffuse mediastinal lymphadenopathy who was diagnosed with metastatic bladder cancer without a primary bladder tumor mass on imaging.

CASE DESCRIPTION

A 60-year-old man with a 60 pack-year smoking history, alcoholic cirrhosis, and a 5-year history of stage 1 CLL presented with 3 months of progressive shortness of breath; persistent cough; chills; hemoptysis; and a steady weight loss of 35 lbs. Notably, he had no bladder symptoms. Initial labs showed leukocytosis of 35.8k with a lymphocytic predominance. Screening low-dose chest CT was positive for diffuse mediastinal lymphadenopathy. Subsequent PET/CT revealed numerous hypermetabolic lymph nodes in the neck, mediastinum, left hilum, and right periaortic abdominal region. CT Chest, Abdomen, Pelvis revealed progressive lymphadenopathy as seen in prior imaging, stable pulmonary nodules up to 4 mm in size, and splenomegaly. No distant primary sites, including of the bladder, were identified. Mediastinal lymph node biopsy confirmed metastatic poorly differentiated carcinoma with immunohistochemical staining negative for p40, p63, CK20, TTF-1, Napsin A, CDX2, CA19- 9, Calretinin, and D2-40 and positive for CK7, GATA3, Ber-EP4, and Uroplakin, supporting bladder as primary origin. Urology deferred a cystoscopy given his lack of urinary symptoms and positive biopsy and was started on Carboplatin/Gemcitabine for his metastatic disease. He was ineligible for Cisplatin given his cirrhosis and hearing impairment.

DISCUSSION

In patients with CLL, new onset mediastinal lymphadenopathy is concerning for disease progression and possible transformation to a diffuse b-cell lymphoma. However, this symptom has a broad differential, including primary lung carcinomas, sarcomas, and metastatic disease. While our patient’s PET/CT and pan-CT failed to identify a distant primary site, maintaining a low clinical suspicion for metastatic disease and doing a thorough work-up was paramount. Only through immunohistochemical staining were we able to diagnosis this patient with urothelial carcinoma.

CONCLUSIONS

Biopsy with immunohistochemical staining and maintaining a low suspicion for worsening lymphadenopathy can identify unusually presenting urothelial carcinomas in CLL patients.

INTRODUCTION

Lymphadenopathy in Chronic Lymphocytic Leukemia (CLL) is a very common feature. However, sudden increase in lymphadenopathy or other symptoms like weight loss should be evaluated for possible metastatic malignancy. We describe a CLL patient with diffuse mediastinal lymphadenopathy who was diagnosed with metastatic bladder cancer without a primary bladder tumor mass on imaging.

CASE DESCRIPTION

A 60-year-old man with a 60 pack-year smoking history, alcoholic cirrhosis, and a 5-year history of stage 1 CLL presented with 3 months of progressive shortness of breath; persistent cough; chills; hemoptysis; and a steady weight loss of 35 lbs. Notably, he had no bladder symptoms. Initial labs showed leukocytosis of 35.8k with a lymphocytic predominance. Screening low-dose chest CT was positive for diffuse mediastinal lymphadenopathy. Subsequent PET/CT revealed numerous hypermetabolic lymph nodes in the neck, mediastinum, left hilum, and right periaortic abdominal region. CT Chest, Abdomen, Pelvis revealed progressive lymphadenopathy as seen in prior imaging, stable pulmonary nodules up to 4 mm in size, and splenomegaly. No distant primary sites, including of the bladder, were identified. Mediastinal lymph node biopsy confirmed metastatic poorly differentiated carcinoma with immunohistochemical staining negative for p40, p63, CK20, TTF-1, Napsin A, CDX2, CA19- 9, Calretinin, and D2-40 and positive for CK7, GATA3, Ber-EP4, and Uroplakin, supporting bladder as primary origin. Urology deferred a cystoscopy given his lack of urinary symptoms and positive biopsy and was started on Carboplatin/Gemcitabine for his metastatic disease. He was ineligible for Cisplatin given his cirrhosis and hearing impairment.

DISCUSSION

In patients with CLL, new onset mediastinal lymphadenopathy is concerning for disease progression and possible transformation to a diffuse b-cell lymphoma. However, this symptom has a broad differential, including primary lung carcinomas, sarcomas, and metastatic disease. While our patient’s PET/CT and pan-CT failed to identify a distant primary site, maintaining a low clinical suspicion for metastatic disease and doing a thorough work-up was paramount. Only through immunohistochemical staining were we able to diagnosis this patient with urothelial carcinoma.

CONCLUSIONS

Biopsy with immunohistochemical staining and maintaining a low suspicion for worsening lymphadenopathy can identify unusually presenting urothelial carcinomas in CLL patients.

FROM SOHO 2023

It may be possible for patients with Hodgkin lymphoma to safely skip their interim PET-CT scan (PET2) following two cycles of frontline brentuximab vedotin (Adcetris), according to research presented at the annual meeting of the Society of Hematologic Oncology in Houston.

Data from four recent studies indicate that adding frontline brentuximab vedotin to AVD chemotherapy (doxorubicin, vinblastine, dacarbazine) improves outcomes for patients, regardless of PET2 scan results, according to lead investigator Ravand Samaeekia, MD, MSc, from Loma Linda (Calif.) University Medical Center.

These studies, including one conducted by Dr. Samaeekia’s team, provide “evidence for the safe omission of PET2 in treatment regimens that contain brentuximab vedotin,” Dr. Samaeekia, who presented the data, concluded.

Performing an interim PET-CT scan after two cycles of chemotherapy can help oncologists adapt treatment protocols for patients with Hodgkin lymphoma and has become the standard of care for these patients.

However, “there are obviously challenges associated with implementing a PET-guided approach,” said Dr. Samaeekia. Additional PET-CT scans can be costly, time consuming, and increase patients’ risk for toxicities when treatment is escalated based on the scan results.

Given these caveats, Dr. Samaeekia reviewed data exploring whether PET2 has predictive value for patients who receive the anti-CD30 antibody-drug conjugate, brentuximab vedotin, as part of first-line treatment alongside AVD chemotherapy.

Dr. Samaeekia’s team analyzed findings from three trials – ECHELON-1, AHOD1331, and BREACH – which assessed frontline standard of care chemotherapy with or without brentuximab. The team found that incorporating brentuximab into frontline treatment resulted in superior efficacy, and PET2 scans results generally did not change how patients were managed.

In ECHELON-1, 6-year overall survival favored patients with advanced Hodgkin lymphoma who received brentuximab and were PET2 negative (94.9% vs. 90.6%; hazard ratio for death, 0.54) as well as those who were PET2 positive (95% vs. 77%; HR, 0.16). Overall, just over 2% of patients who received the brentuximab regimen switched to an alternative chemotherapy and even fewer did so based on PET2 results.

In AHOD1331, 3-year event-free survival was significantly higher among adolescents and children with Hodgkin lymphoma who received brentuximab – 90.7% for those who had slow-responding lesions and 92.3% for those with rapid-responding lesions. Based on these results, the authors concluded that adding brentuximab “eliminated the predictive value of the interim PET assessment.” The BREACH trial echoed the findings from ECHELON-1 and AHOD1331.

Finally, in a retrospective study of 40 patients treated at Loma Linda with brentuximab vedotin plus AVD, Dr. Samaeekia and colleagues found that 24 were PET2 negative and 12 were PET2 positive. All patients who were PET2 negative remained negative on the end-of-treatment PET, indicating no cancer progression. Of the 12 PET2-positive patients, four (33%) remained PET positive at the end of treatment. Only one patient overall changed regimens following PET2.

Dr. Samaeekia’s team concluded that PET2 scan results “did not have any meaningful impact” on patient management or outcomes.

During the Q&A, Martin Hutchings, MD, PhD, challenged the idea that PET2 can be omitted. Dr. Hutchings, from the Rigshospitalet in Copenhagen, pointed out that 4 of the 12 PET2-positive patients treated at Loma Linda were still PET positive at the end of treatment.

Even so, Dr. Samaeekia explained, PET2 findings did not alter treatment for most patients, noting that doing a PET2 scan may make “us feel better,” but it ultimately doesn’t “make any difference in our management.”

In the AHOD1331 study, “the findings on the interim PET scan were not helpful in the ultimate outcome, whether it was either positive or negative,” added session comoderator Jonathan W. Friedberg, MD, MMSc, director of the James P. Wilmot Cancer Institute at the University of Rochester (N.Y.) Medical Center.

The study by Dr. Samaeekia and colleagues was internally funded. Dr. Samaeekia reports no relevant financial relationships. Dr. Hutchings has previously reported consultancy and research funding from numerous companies. Dr. Friedberg reports no relevant financial relationships.

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

FROM SOHO 2023

It may be possible for patients with Hodgkin lymphoma to safely skip their interim PET-CT scan (PET2) following two cycles of frontline brentuximab vedotin (Adcetris), according to research presented at the annual meeting of the Society of Hematologic Oncology in Houston.

Data from four recent studies indicate that adding frontline brentuximab vedotin to AVD chemotherapy (doxorubicin, vinblastine, dacarbazine) improves outcomes for patients, regardless of PET2 scan results, according to lead investigator Ravand Samaeekia, MD, MSc, from Loma Linda (Calif.) University Medical Center.

These studies, including one conducted by Dr. Samaeekia’s team, provide “evidence for the safe omission of PET2 in treatment regimens that contain brentuximab vedotin,” Dr. Samaeekia, who presented the data, concluded.

Performing an interim PET-CT scan after two cycles of chemotherapy can help oncologists adapt treatment protocols for patients with Hodgkin lymphoma and has become the standard of care for these patients.

However, “there are obviously challenges associated with implementing a PET-guided approach,” said Dr. Samaeekia. Additional PET-CT scans can be costly, time consuming, and increase patients’ risk for toxicities when treatment is escalated based on the scan results.

Given these caveats, Dr. Samaeekia reviewed data exploring whether PET2 has predictive value for patients who receive the anti-CD30 antibody-drug conjugate, brentuximab vedotin, as part of first-line treatment alongside AVD chemotherapy.

Dr. Samaeekia’s team analyzed findings from three trials – ECHELON-1, AHOD1331, and BREACH – which assessed frontline standard of care chemotherapy with or without brentuximab. The team found that incorporating brentuximab into frontline treatment resulted in superior efficacy, and PET2 scans results generally did not change how patients were managed.

In ECHELON-1, 6-year overall survival favored patients with advanced Hodgkin lymphoma who received brentuximab and were PET2 negative (94.9% vs. 90.6%; hazard ratio for death, 0.54) as well as those who were PET2 positive (95% vs. 77%; HR, 0.16). Overall, just over 2% of patients who received the brentuximab regimen switched to an alternative chemotherapy and even fewer did so based on PET2 results.

In AHOD1331, 3-year event-free survival was significantly higher among adolescents and children with Hodgkin lymphoma who received brentuximab – 90.7% for those who had slow-responding lesions and 92.3% for those with rapid-responding lesions. Based on these results, the authors concluded that adding brentuximab “eliminated the predictive value of the interim PET assessment.” The BREACH trial echoed the findings from ECHELON-1 and AHOD1331.

Finally, in a retrospective study of 40 patients treated at Loma Linda with brentuximab vedotin plus AVD, Dr. Samaeekia and colleagues found that 24 were PET2 negative and 12 were PET2 positive. All patients who were PET2 negative remained negative on the end-of-treatment PET, indicating no cancer progression. Of the 12 PET2-positive patients, four (33%) remained PET positive at the end of treatment. Only one patient overall changed regimens following PET2.

Dr. Samaeekia’s team concluded that PET2 scan results “did not have any meaningful impact” on patient management or outcomes.

During the Q&A, Martin Hutchings, MD, PhD, challenged the idea that PET2 can be omitted. Dr. Hutchings, from the Rigshospitalet in Copenhagen, pointed out that 4 of the 12 PET2-positive patients treated at Loma Linda were still PET positive at the end of treatment.

Even so, Dr. Samaeekia explained, PET2 findings did not alter treatment for most patients, noting that doing a PET2 scan may make “us feel better,” but it ultimately doesn’t “make any difference in our management.”

In the AHOD1331 study, “the findings on the interim PET scan were not helpful in the ultimate outcome, whether it was either positive or negative,” added session comoderator Jonathan W. Friedberg, MD, MMSc, director of the James P. Wilmot Cancer Institute at the University of Rochester (N.Y.) Medical Center.

The study by Dr. Samaeekia and colleagues was internally funded. Dr. Samaeekia reports no relevant financial relationships. Dr. Hutchings has previously reported consultancy and research funding from numerous companies. Dr. Friedberg reports no relevant financial relationships.

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

FROM SOHO 2023

It may be possible for patients with Hodgkin lymphoma to safely skip their interim PET-CT scan (PET2) following two cycles of frontline brentuximab vedotin (Adcetris), according to research presented at the annual meeting of the Society of Hematologic Oncology in Houston.

Data from four recent studies indicate that adding frontline brentuximab vedotin to AVD chemotherapy (doxorubicin, vinblastine, dacarbazine) improves outcomes for patients, regardless of PET2 scan results, according to lead investigator Ravand Samaeekia, MD, MSc, from Loma Linda (Calif.) University Medical Center.

These studies, including one conducted by Dr. Samaeekia’s team, provide “evidence for the safe omission of PET2 in treatment regimens that contain brentuximab vedotin,” Dr. Samaeekia, who presented the data, concluded.

Performing an interim PET-CT scan after two cycles of chemotherapy can help oncologists adapt treatment protocols for patients with Hodgkin lymphoma and has become the standard of care for these patients.

However, “there are obviously challenges associated with implementing a PET-guided approach,” said Dr. Samaeekia. Additional PET-CT scans can be costly, time consuming, and increase patients’ risk for toxicities when treatment is escalated based on the scan results.

Given these caveats, Dr. Samaeekia reviewed data exploring whether PET2 has predictive value for patients who receive the anti-CD30 antibody-drug conjugate, brentuximab vedotin, as part of first-line treatment alongside AVD chemotherapy.

Dr. Samaeekia’s team analyzed findings from three trials – ECHELON-1, AHOD1331, and BREACH – which assessed frontline standard of care chemotherapy with or without brentuximab. The team found that incorporating brentuximab into frontline treatment resulted in superior efficacy, and PET2 scans results generally did not change how patients were managed.

In ECHELON-1, 6-year overall survival favored patients with advanced Hodgkin lymphoma who received brentuximab and were PET2 negative (94.9% vs. 90.6%; hazard ratio for death, 0.54) as well as those who were PET2 positive (95% vs. 77%; HR, 0.16). Overall, just over 2% of patients who received the brentuximab regimen switched to an alternative chemotherapy and even fewer did so based on PET2 results.

In AHOD1331, 3-year event-free survival was significantly higher among adolescents and children with Hodgkin lymphoma who received brentuximab – 90.7% for those who had slow-responding lesions and 92.3% for those with rapid-responding lesions. Based on these results, the authors concluded that adding brentuximab “eliminated the predictive value of the interim PET assessment.” The BREACH trial echoed the findings from ECHELON-1 and AHOD1331.

Finally, in a retrospective study of 40 patients treated at Loma Linda with brentuximab vedotin plus AVD, Dr. Samaeekia and colleagues found that 24 were PET2 negative and 12 were PET2 positive. All patients who were PET2 negative remained negative on the end-of-treatment PET, indicating no cancer progression. Of the 12 PET2-positive patients, four (33%) remained PET positive at the end of treatment. Only one patient overall changed regimens following PET2.

Dr. Samaeekia’s team concluded that PET2 scan results “did not have any meaningful impact” on patient management or outcomes.

During the Q&A, Martin Hutchings, MD, PhD, challenged the idea that PET2 can be omitted. Dr. Hutchings, from the Rigshospitalet in Copenhagen, pointed out that 4 of the 12 PET2-positive patients treated at Loma Linda were still PET positive at the end of treatment.

Even so, Dr. Samaeekia explained, PET2 findings did not alter treatment for most patients, noting that doing a PET2 scan may make “us feel better,” but it ultimately doesn’t “make any difference in our management.”

In the AHOD1331 study, “the findings on the interim PET scan were not helpful in the ultimate outcome, whether it was either positive or negative,” added session comoderator Jonathan W. Friedberg, MD, MMSc, director of the James P. Wilmot Cancer Institute at the University of Rochester (N.Y.) Medical Center.

The study by Dr. Samaeekia and colleagues was internally funded. Dr. Samaeekia reports no relevant financial relationships. Dr. Hutchings has previously reported consultancy and research funding from numerous companies. Dr. Friedberg reports no relevant financial relationships.

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

Patients with cutaneous Merkel cell carcinoma (MCC) have a higher risk of subsequently developing solid and hematologic cancers, according to a new analysis.

In a cohort of 6,146 patients with a first primary MCC, a total of 725 (11.8%) developed subsequent primary cancers. For solid tumors, the risk was highest for cutaneous melanoma and papillary thyroid carcinoma, while for hematologic cancers, the risk was increased for non-Hodgkin lymphoma.

“Our study does confirm that patients with MCC are at higher risk for developing other cancers,” study author Lisa C. Zaba, MD, PhD, associate professor of dermatology and director of the Merkel cell carcinoma multidisciplinary clinic, Stanford (Calif.) Cancer Center, said in an interview. “MCC is a highly malignant cancer with a 40% recurrence risk.”

Because of this high risk, Dr. Zaba noted that patients with MCC get frequent surveillance with both imaging studies (PET-CT and CT) as well as frequent visits in clinic with MCC experts. “Specifically, a patient with MCC is imaged and seen in clinic every 3-6 months for the first 3 years after diagnosis, and every 6-12 months thereafter for up to 5 years,” she said. “Interestingly, this high level of surveillance may be one reason that we find so many cancers in patients who have been diagnosed with MCC, compared to the general population.”

The study was published online in JAMA Dermatology.

With the death of “Margaritaville” singer Jimmy Buffett, who recently died of MCC 4 years after his diagnosis, this rare, aggressive skin cancer has been put in the spotlight. Survival has been increasing, primarily because of the advent of immunotherapy, and the authors note that it is therefore imperative to better understand the risk of subsequent primary tumors to inform screening and treatment recommendations.

In this cohort study, Dr. Zaba and colleagues identified 6,146 patients from 17 registries of the Surveillance, Epidemiology, and End Results (SEER) Program who had been diagnosed with a first primary cutaneous MCC between 2000 and 2018.

Endpoints were the ratio of observed to expected number of cases of subsequent cancer (Standardized incidence ratio, or SIR) and the excess risk.

Overall, there was an elevated risk of developing a subsequent primary cancer after being diagnosed with MCC (SIR, 1.28; excess risk, 57.25 per 10,000 person-years). This included the risk for all solid tumors including liver (SIR, 1.92; excess risk, 2.77 per 10,000 person-years), pancreas (SIR, 1.65; excess risk, 4.55 per 10,000 person-years), cutaneous melanoma (SIR, 2.36; excess risk, 15.27 per 10,000 person-years), and kidney (SIR, 1.64; excess risk, 3.83 per 10,000 person-years).

There was also a higher risk of developing papillary thyroid carcinoma (PTC) (SIR, 5.26; excess risk, 6.16 per 10,000 person-years).

The risk of developing hematological cancers after MCC was also increased, especially for non-Hodgkin lymphoma (SIR, 2.62; excess risk, 15.48 per 10,000 person-years) and myelodysplastic syndrome (SIR, 2.17; excess risk, 2.73 per 10,000 person-years).

The risk for developing subsequent tumors, including melanoma and non-Hodgkin lymphoma, remained significant for up to 10 years, while the risk for developing PTC and kidney cancers remained for up to 5 years.

“After 3-5 years, when a MCC patient’s risk of MCC recurrence drops below 2%, we do not currently have guidelines in place for additional cancer screening,” Dr. Zaba said. “Regarding patient education, patients with MCC are educated to let us know if they experience any symptoms of cancer between visits, including unintentional weight loss, night sweats, headaches that increasingly worsen, or growing lumps or bumps. These symptoms may occur in a multitude of cancers and not just MCC.”

Weighing in on the study, Jeffrey M. Farma, MD, interim chair, department of surgical oncology at Fox Chase Cancer Center, Philadelphia, noted that MCC is considered to be high risk because of its chances of recurring after surgical resection or spreading to lymph nodes or other areas of the body. “There are approximately 3,000 new cases of melanoma a year in the U.S., and it is 40 times rarer than melanoma,” he said. “Patients are usually diagnosed with Merkel cell carcinoma later in life, and the tumors have been associated with sun exposure and immunosuppression and have also been associated with the polyomavirus.”

That said, however, he emphasized that great strides have been made in treatment. “These tumors are very sensitive to radiation, and we generally treat earlier-stage MCC with a combination of surgery and radiation therapy,” said Dr. Farma. “More recently we have had a lot of success with the use of immunotherapy to treat more advanced MCC.”

Dr. Zaba reported receiving grants from the Kuni Foundation outside the submitted work. No other disclosures were reported. Author Eleni Linos, MD, DrPH, MPH, is supported by grant K24AR075060 from the National Institutes of Health. No other outside funding was reported. Dr. Farma had no disclosures.

Patients with cutaneous Merkel cell carcinoma (MCC) have a higher risk of subsequently developing solid and hematologic cancers, according to a new analysis.

In a cohort of 6,146 patients with a first primary MCC, a total of 725 (11.8%) developed subsequent primary cancers. For solid tumors, the risk was highest for cutaneous melanoma and papillary thyroid carcinoma, while for hematologic cancers, the risk was increased for non-Hodgkin lymphoma.

“Our study does confirm that patients with MCC are at higher risk for developing other cancers,” study author Lisa C. Zaba, MD, PhD, associate professor of dermatology and director of the Merkel cell carcinoma multidisciplinary clinic, Stanford (Calif.) Cancer Center, said in an interview. “MCC is a highly malignant cancer with a 40% recurrence risk.”

Because of this high risk, Dr. Zaba noted that patients with MCC get frequent surveillance with both imaging studies (PET-CT and CT) as well as frequent visits in clinic with MCC experts. “Specifically, a patient with MCC is imaged and seen in clinic every 3-6 months for the first 3 years after diagnosis, and every 6-12 months thereafter for up to 5 years,” she said. “Interestingly, this high level of surveillance may be one reason that we find so many cancers in patients who have been diagnosed with MCC, compared to the general population.”

The study was published online in JAMA Dermatology.

With the death of “Margaritaville” singer Jimmy Buffett, who recently died of MCC 4 years after his diagnosis, this rare, aggressive skin cancer has been put in the spotlight. Survival has been increasing, primarily because of the advent of immunotherapy, and the authors note that it is therefore imperative to better understand the risk of subsequent primary tumors to inform screening and treatment recommendations.

In this cohort study, Dr. Zaba and colleagues identified 6,146 patients from 17 registries of the Surveillance, Epidemiology, and End Results (SEER) Program who had been diagnosed with a first primary cutaneous MCC between 2000 and 2018.

Endpoints were the ratio of observed to expected number of cases of subsequent cancer (Standardized incidence ratio, or SIR) and the excess risk.

Overall, there was an elevated risk of developing a subsequent primary cancer after being diagnosed with MCC (SIR, 1.28; excess risk, 57.25 per 10,000 person-years). This included the risk for all solid tumors including liver (SIR, 1.92; excess risk, 2.77 per 10,000 person-years), pancreas (SIR, 1.65; excess risk, 4.55 per 10,000 person-years), cutaneous melanoma (SIR, 2.36; excess risk, 15.27 per 10,000 person-years), and kidney (SIR, 1.64; excess risk, 3.83 per 10,000 person-years).

There was also a higher risk of developing papillary thyroid carcinoma (PTC) (SIR, 5.26; excess risk, 6.16 per 10,000 person-years).

The risk of developing hematological cancers after MCC was also increased, especially for non-Hodgkin lymphoma (SIR, 2.62; excess risk, 15.48 per 10,000 person-years) and myelodysplastic syndrome (SIR, 2.17; excess risk, 2.73 per 10,000 person-years).

The risk for developing subsequent tumors, including melanoma and non-Hodgkin lymphoma, remained significant for up to 10 years, while the risk for developing PTC and kidney cancers remained for up to 5 years.

“After 3-5 years, when a MCC patient’s risk of MCC recurrence drops below 2%, we do not currently have guidelines in place for additional cancer screening,” Dr. Zaba said. “Regarding patient education, patients with MCC are educated to let us know if they experience any symptoms of cancer between visits, including unintentional weight loss, night sweats, headaches that increasingly worsen, or growing lumps or bumps. These symptoms may occur in a multitude of cancers and not just MCC.”

Weighing in on the study, Jeffrey M. Farma, MD, interim chair, department of surgical oncology at Fox Chase Cancer Center, Philadelphia, noted that MCC is considered to be high risk because of its chances of recurring after surgical resection or spreading to lymph nodes or other areas of the body. “There are approximately 3,000 new cases of melanoma a year in the U.S., and it is 40 times rarer than melanoma,” he said. “Patients are usually diagnosed with Merkel cell carcinoma later in life, and the tumors have been associated with sun exposure and immunosuppression and have also been associated with the polyomavirus.”

That said, however, he emphasized that great strides have been made in treatment. “These tumors are very sensitive to radiation, and we generally treat earlier-stage MCC with a combination of surgery and radiation therapy,” said Dr. Farma. “More recently we have had a lot of success with the use of immunotherapy to treat more advanced MCC.”

Dr. Zaba reported receiving grants from the Kuni Foundation outside the submitted work. No other disclosures were reported. Author Eleni Linos, MD, DrPH, MPH, is supported by grant K24AR075060 from the National Institutes of Health. No other outside funding was reported. Dr. Farma had no disclosures.

Patients with cutaneous Merkel cell carcinoma (MCC) have a higher risk of subsequently developing solid and hematologic cancers, according to a new analysis.

In a cohort of 6,146 patients with a first primary MCC, a total of 725 (11.8%) developed subsequent primary cancers. For solid tumors, the risk was highest for cutaneous melanoma and papillary thyroid carcinoma, while for hematologic cancers, the risk was increased for non-Hodgkin lymphoma.

“Our study does confirm that patients with MCC are at higher risk for developing other cancers,” study author Lisa C. Zaba, MD, PhD, associate professor of dermatology and director of the Merkel cell carcinoma multidisciplinary clinic, Stanford (Calif.) Cancer Center, said in an interview. “MCC is a highly malignant cancer with a 40% recurrence risk.”

Because of this high risk, Dr. Zaba noted that patients with MCC get frequent surveillance with both imaging studies (PET-CT and CT) as well as frequent visits in clinic with MCC experts. “Specifically, a patient with MCC is imaged and seen in clinic every 3-6 months for the first 3 years after diagnosis, and every 6-12 months thereafter for up to 5 years,” she said. “Interestingly, this high level of surveillance may be one reason that we find so many cancers in patients who have been diagnosed with MCC, compared to the general population.”

The study was published online in JAMA Dermatology.

With the death of “Margaritaville” singer Jimmy Buffett, who recently died of MCC 4 years after his diagnosis, this rare, aggressive skin cancer has been put in the spotlight. Survival has been increasing, primarily because of the advent of immunotherapy, and the authors note that it is therefore imperative to better understand the risk of subsequent primary tumors to inform screening and treatment recommendations.

In this cohort study, Dr. Zaba and colleagues identified 6,146 patients from 17 registries of the Surveillance, Epidemiology, and End Results (SEER) Program who had been diagnosed with a first primary cutaneous MCC between 2000 and 2018.

Endpoints were the ratio of observed to expected number of cases of subsequent cancer (Standardized incidence ratio, or SIR) and the excess risk.

Overall, there was an elevated risk of developing a subsequent primary cancer after being diagnosed with MCC (SIR, 1.28; excess risk, 57.25 per 10,000 person-years). This included the risk for all solid tumors including liver (SIR, 1.92; excess risk, 2.77 per 10,000 person-years), pancreas (SIR, 1.65; excess risk, 4.55 per 10,000 person-years), cutaneous melanoma (SIR, 2.36; excess risk, 15.27 per 10,000 person-years), and kidney (SIR, 1.64; excess risk, 3.83 per 10,000 person-years).

There was also a higher risk of developing papillary thyroid carcinoma (PTC) (SIR, 5.26; excess risk, 6.16 per 10,000 person-years).

The risk of developing hematological cancers after MCC was also increased, especially for non-Hodgkin lymphoma (SIR, 2.62; excess risk, 15.48 per 10,000 person-years) and myelodysplastic syndrome (SIR, 2.17; excess risk, 2.73 per 10,000 person-years).

The risk for developing subsequent tumors, including melanoma and non-Hodgkin lymphoma, remained significant for up to 10 years, while the risk for developing PTC and kidney cancers remained for up to 5 years.

“After 3-5 years, when a MCC patient’s risk of MCC recurrence drops below 2%, we do not currently have guidelines in place for additional cancer screening,” Dr. Zaba said. “Regarding patient education, patients with MCC are educated to let us know if they experience any symptoms of cancer between visits, including unintentional weight loss, night sweats, headaches that increasingly worsen, or growing lumps or bumps. These symptoms may occur in a multitude of cancers and not just MCC.”

Weighing in on the study, Jeffrey M. Farma, MD, interim chair, department of surgical oncology at Fox Chase Cancer Center, Philadelphia, noted that MCC is considered to be high risk because of its chances of recurring after surgical resection or spreading to lymph nodes or other areas of the body. “There are approximately 3,000 new cases of melanoma a year in the U.S., and it is 40 times rarer than melanoma,” he said. “Patients are usually diagnosed with Merkel cell carcinoma later in life, and the tumors have been associated with sun exposure and immunosuppression and have also been associated with the polyomavirus.”

That said, however, he emphasized that great strides have been made in treatment. “These tumors are very sensitive to radiation, and we generally treat earlier-stage MCC with a combination of surgery and radiation therapy,” said Dr. Farma. “More recently we have had a lot of success with the use of immunotherapy to treat more advanced MCC.”

Dr. Zaba reported receiving grants from the Kuni Foundation outside the submitted work. No other disclosures were reported. Author Eleni Linos, MD, DrPH, MPH, is supported by grant K24AR075060 from the National Institutes of Health. No other outside funding was reported. Dr. Farma had no disclosures.