TBD Meeting (5431-21)

The International Cancer Benchmarking Partnership, a collaboration of physicians, clinicians, researchers, policy makers, and data experts, has reached a consensus on key actions designed to standardize and homogenize lung cancer care that includes early diagnosis and access to care for all patients.

This consensus, reported at the 2022 European Lung Cancer Congress, is an effort to address disparities in care recognized by the group’s in-house research team. The team identified significantly different survival rates in early stage lung cancer patients from a group of countries with similar health care metrics, such as health care expenditure and universal access to health care.

“This group of countries is very comparable, but we saw a 20% difference in survival in localized, stage I and II cancers. When you consider that lung cancer is a bigger killer than any other cancer –more than breast, prostate, and colon cancer combined – that’s thousands of people,” said the project’s lead clinician, Christian Finley, MD, a thoracic surgeon with St. Joseph’s Healthcare Hamilton (Ont.).

Founded in 2009, the ICBP includes about 500 experts in its core countries of Sweden, Norway, Denmark, Australia, the United Kingdom, and Canada; New Zealand and Ireland have also participated. The goal of the partnership is to benchmark survival and other outcomes in cancer and to research why disparities between countries exist.

“That’s why we keep the membership fairly small, so that we can actually make more meaningful research projects to get into depth in factors beyond benchmarking survival and mortality,” said study author Charlotte Lynch, MSc, a senior researcher with Cancer Research UK in London.

To help narrow the disparity gap, Ms. Lynch, Dr. Finley and colleagues brought together nine key informants from ICBP countries to discuss local clinical insights and best practices, and ultimately came up a list of five recommendations considered most crucial: implementing cost-effective, equitable, and effective screening; ensuring diagnoses of lung cancer within 30 days of referral; developing thoracic centers of excellence; launching an international audit of lung cancer care; and prioritizing the recognition of improvements in lung cancer care and outcomes.

They identified 13 best practice points to support the development and implementation of the calls to action.

“For example, points supporting the screening call to action focus on timely access to cross-sectional imaging and availability and development of patient and health care practitioner lung cancer awareness materials,” Ms. Lynch said.

Another example would be the point that describes the need for a minimum data set to evaluate lung cancer patients’ diagnosis, treatment, and aftercare.

“I think we all work in a very disrupted system right now. Screening programs really took a hit during the pandemic, and I think people coming out of those disruptions are trying to imagine a more effective system using tools like information technologies, mobile clinics and having a better understanding of equity,” Dr. Finley said.

Ms. Lynch said the ICBP intends to use the consensus to generate concrete actions. “We’re thinking about how we can get everyone in the room to share lessons learned and best practices to push things forward rather than saying, ‘this is what should be done,’ making sure we do the next steps, collaborative thinking, and moving forward.”

In a press release, Antonio Passaro, MD, a lung cancer expert from the European Institute of Oncology in Milan, said there is a need to prioritize primary and secondary prevention of lung cancer.

“Although a much-debated topic in recent years, a strong body of research has now shown that lung cancer screening through annual computed tomography scans in individuals with a history of smoking can improve detection rates. Targeting the right populations with these interventions will be crucial to implementing screening approaches that are both efficacious and cost effective,” he stated.

The authors declared no conflicts of interest and this study was not funded.

The International Cancer Benchmarking Partnership, a collaboration of physicians, clinicians, researchers, policy makers, and data experts, has reached a consensus on key actions designed to standardize and homogenize lung cancer care that includes early diagnosis and access to care for all patients.

This consensus, reported at the 2022 European Lung Cancer Congress, is an effort to address disparities in care recognized by the group’s in-house research team. The team identified significantly different survival rates in early stage lung cancer patients from a group of countries with similar health care metrics, such as health care expenditure and universal access to health care.

“This group of countries is very comparable, but we saw a 20% difference in survival in localized, stage I and II cancers. When you consider that lung cancer is a bigger killer than any other cancer –more than breast, prostate, and colon cancer combined – that’s thousands of people,” said the project’s lead clinician, Christian Finley, MD, a thoracic surgeon with St. Joseph’s Healthcare Hamilton (Ont.).

Founded in 2009, the ICBP includes about 500 experts in its core countries of Sweden, Norway, Denmark, Australia, the United Kingdom, and Canada; New Zealand and Ireland have also participated. The goal of the partnership is to benchmark survival and other outcomes in cancer and to research why disparities between countries exist.

“That’s why we keep the membership fairly small, so that we can actually make more meaningful research projects to get into depth in factors beyond benchmarking survival and mortality,” said study author Charlotte Lynch, MSc, a senior researcher with Cancer Research UK in London.

To help narrow the disparity gap, Ms. Lynch, Dr. Finley and colleagues brought together nine key informants from ICBP countries to discuss local clinical insights and best practices, and ultimately came up a list of five recommendations considered most crucial: implementing cost-effective, equitable, and effective screening; ensuring diagnoses of lung cancer within 30 days of referral; developing thoracic centers of excellence; launching an international audit of lung cancer care; and prioritizing the recognition of improvements in lung cancer care and outcomes.

They identified 13 best practice points to support the development and implementation of the calls to action.

“For example, points supporting the screening call to action focus on timely access to cross-sectional imaging and availability and development of patient and health care practitioner lung cancer awareness materials,” Ms. Lynch said.

Another example would be the point that describes the need for a minimum data set to evaluate lung cancer patients’ diagnosis, treatment, and aftercare.

“I think we all work in a very disrupted system right now. Screening programs really took a hit during the pandemic, and I think people coming out of those disruptions are trying to imagine a more effective system using tools like information technologies, mobile clinics and having a better understanding of equity,” Dr. Finley said.

Ms. Lynch said the ICBP intends to use the consensus to generate concrete actions. “We’re thinking about how we can get everyone in the room to share lessons learned and best practices to push things forward rather than saying, ‘this is what should be done,’ making sure we do the next steps, collaborative thinking, and moving forward.”

In a press release, Antonio Passaro, MD, a lung cancer expert from the European Institute of Oncology in Milan, said there is a need to prioritize primary and secondary prevention of lung cancer.

“Although a much-debated topic in recent years, a strong body of research has now shown that lung cancer screening through annual computed tomography scans in individuals with a history of smoking can improve detection rates. Targeting the right populations with these interventions will be crucial to implementing screening approaches that are both efficacious and cost effective,” he stated.

The authors declared no conflicts of interest and this study was not funded.

The International Cancer Benchmarking Partnership, a collaboration of physicians, clinicians, researchers, policy makers, and data experts, has reached a consensus on key actions designed to standardize and homogenize lung cancer care that includes early diagnosis and access to care for all patients.

This consensus, reported at the 2022 European Lung Cancer Congress, is an effort to address disparities in care recognized by the group’s in-house research team. The team identified significantly different survival rates in early stage lung cancer patients from a group of countries with similar health care metrics, such as health care expenditure and universal access to health care.

“This group of countries is very comparable, but we saw a 20% difference in survival in localized, stage I and II cancers. When you consider that lung cancer is a bigger killer than any other cancer –more than breast, prostate, and colon cancer combined – that’s thousands of people,” said the project’s lead clinician, Christian Finley, MD, a thoracic surgeon with St. Joseph’s Healthcare Hamilton (Ont.).

Founded in 2009, the ICBP includes about 500 experts in its core countries of Sweden, Norway, Denmark, Australia, the United Kingdom, and Canada; New Zealand and Ireland have also participated. The goal of the partnership is to benchmark survival and other outcomes in cancer and to research why disparities between countries exist.

“That’s why we keep the membership fairly small, so that we can actually make more meaningful research projects to get into depth in factors beyond benchmarking survival and mortality,” said study author Charlotte Lynch, MSc, a senior researcher with Cancer Research UK in London.

To help narrow the disparity gap, Ms. Lynch, Dr. Finley and colleagues brought together nine key informants from ICBP countries to discuss local clinical insights and best practices, and ultimately came up a list of five recommendations considered most crucial: implementing cost-effective, equitable, and effective screening; ensuring diagnoses of lung cancer within 30 days of referral; developing thoracic centers of excellence; launching an international audit of lung cancer care; and prioritizing the recognition of improvements in lung cancer care and outcomes.

They identified 13 best practice points to support the development and implementation of the calls to action.

“For example, points supporting the screening call to action focus on timely access to cross-sectional imaging and availability and development of patient and health care practitioner lung cancer awareness materials,” Ms. Lynch said.

Another example would be the point that describes the need for a minimum data set to evaluate lung cancer patients’ diagnosis, treatment, and aftercare.

“I think we all work in a very disrupted system right now. Screening programs really took a hit during the pandemic, and I think people coming out of those disruptions are trying to imagine a more effective system using tools like information technologies, mobile clinics and having a better understanding of equity,” Dr. Finley said.

Ms. Lynch said the ICBP intends to use the consensus to generate concrete actions. “We’re thinking about how we can get everyone in the room to share lessons learned and best practices to push things forward rather than saying, ‘this is what should be done,’ making sure we do the next steps, collaborative thinking, and moving forward.”

In a press release, Antonio Passaro, MD, a lung cancer expert from the European Institute of Oncology in Milan, said there is a need to prioritize primary and secondary prevention of lung cancer.

“Although a much-debated topic in recent years, a strong body of research has now shown that lung cancer screening through annual computed tomography scans in individuals with a history of smoking can improve detection rates. Targeting the right populations with these interventions will be crucial to implementing screening approaches that are both efficacious and cost effective,” he stated.

The authors declared no conflicts of interest and this study was not funded.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

An increase in the use of hypofractionated radiotherapy for lung cancer has been one of the many consequences of the COVID-19 pandemic, according to initial data from the COVID-RT Lung study.

The U.K.-based study showed that patients with stage I-III lung cancer who were set to undergo radiotherapy with curative intent were more likely to receive fewer fractions at higher doses when treated between April and October 2020. During that period, 19% of patients had their radiotherapy dose or fractionation schedule changed to deviate from standard care.

In addition, 8% of patients who were set to undergo surgery ultimately received radiotherapy instead, presumably to ease pressures on already struggling intensive care services, said Kathryn Banfill, MBChB, of Christie NHS Foundation Trust in Manchester, England.

Dr. Banfill presented results from the COVID-RT Lung study at the European Lung Cancer Virtual Congress 2021 (Abstract 203MO).


 

New guidelines prompt study

When the COVID-19 pandemic began, European and joint European and North American guidelines were issued to try to ensure that lung cancer patients would continue to receive the best possible treatment under the circumstances. This included guidance on how and when to use treatments such as radiotherapy.

One U.K. guideline included recommendations on the use of hypofractionation in the COVID-19 era. The recommendations focused on altering the dosage or length of radiotherapy treatments to try to reduce the number of hospital visits, thereby reducing the risk of exposing patients to SARS-CoV-2.

“The aim of these guidelines is very much to reduce the risk to patients,” Dr. Banfill said. “These patients are often at higher risk of serious COVID-19, both as a result of their cancer and also as a result of many of the coexisting medical conditions that they have, such as COPD [chronic obstructive pulmonary disease],” she explained.

The COVID-RT Lung study was essentially born out of these guidelines. The goals of the study were to see what changes to radiotherapy practice occurred as a result of the guidelines and to assess how the changes have affected patient outcomes.
 

Changes to diagnosis and treatment

COVID-RT Lung is an ongoing, prospective study of patients with biopsy- or imaging-proven stage I–III lung cancer who were referred for, or treated with, radical radiotherapy at one of 26 oncology centers in the United Kingdom between April and October 2020.

Records on 1,117 patients were available for the initial analysis. The patients’ median age was 72 years (range, 38-93 years), and half were women.

The records showed changes to diagnostic investigations in 14% of patients (n = 160). Changes included not obtaining histology (4.6%, n = 51), not conducting nodal sampling (3.1%, n = 35), not performing pulmonary function tests (1.8%, n = 20), not conducting brain imaging (2.9%, n = 32), not performing PET/CT scans or having out-of-date scans (4.2%, n = 47), and delays in diagnosis (0.6%, n = 7).

Changes to treatment – deviations from standard care – occurred in 37% of patients (n = 415). This included 19% of patients (n = 210) having changes to radiotherapy dose or fractionation schedule, 8% (n = 86) undergoing radiotherapy instead of surgery, and 13% (n = 143) having their chemotherapy omitted or reduced.

The median number of radiotherapy fractions was 15 for patients who had their radiotherapy adjusted and 20 for those who had no treatment amendments.

“Those who had their treatment changed were more likely to have hypofractionated or ultra-hypofractionated radiotherapy,” Dr. Banfill said.

This was particularly true for patients with early-stage disease, she noted, where there was an increase in the percentage of patients getting more than 15 Gy per fraction. Even in stage III disease, there was an increased use of 3–5 Gy per fraction, although “virtually nobody” who had a change in treatment received less than 2 Gy per fraction, Dr. Banfill said.

“The changes are in line with what was reported in international recommendations,” observed Yolande Lievens, MD, PhD, of Ghent University Hospital in Belgium, who discussed the findings at the meeting.
 

Few patients had COVID-19

“It was striking to me to see that so few patients developed COVID-19 prior to radiotherapy or during radiotherapy,” Dr. Lievens noted. “This is actually something that we’ve also experienced in our setting.”

Indeed, just 15 patients (1%) were diagnosed with COVID-19, 10 of whom were diagnosed before receiving radiotherapy.

Dr. Banfill observed that the COVID-19 diagnosis had been “a reasonable time” before the patients started radiotherapy, and some had been diagnosed with lung cancer as a result of having a chest x-ray for suspected COVID-19.

Of the four patients who were diagnosed during treatment, two had their radiotherapy interrupted as a result.

The low COVID-19 rate is perhaps a result of the protective measures recommended in the United Kingdom, such as advising patients to shield from others, Dr. Banfill said.
 

Are changes to practice likely to hold?

“Part of the reason we actually stopped the data collection in October was that people were starting to go, ‘Well, is this actually a change?’ because they’d been doing it for 6 months,” Dr. Banfill observed during the discussion session.

“It was becoming almost normal for some of these hypofractionated changes. I think there is potential for these to become more embedded going forward,” she said. Data on how these changes might affect patients in the long term is going to be the focus of a future analysis.

“There is ongoing data collection on recurrence and survival and toxicity, which will hopefully provide more information on the outcomes of this patient group,” Dr. Banfill said.

The COVID-RT Lung project is supported by the NIHR Manchester Biomedical Research Centre. Dr. Banfill and Dr. Lievens reported no relevant conflicts of interest.

An increase in the use of hypofractionated radiotherapy for lung cancer has been one of the many consequences of the COVID-19 pandemic, according to initial data from the COVID-RT Lung study.

The U.K.-based study showed that patients with stage I-III lung cancer who were set to undergo radiotherapy with curative intent were more likely to receive fewer fractions at higher doses when treated between April and October 2020. During that period, 19% of patients had their radiotherapy dose or fractionation schedule changed to deviate from standard care.

In addition, 8% of patients who were set to undergo surgery ultimately received radiotherapy instead, presumably to ease pressures on already struggling intensive care services, said Kathryn Banfill, MBChB, of Christie NHS Foundation Trust in Manchester, England.

Dr. Banfill presented results from the COVID-RT Lung study at the European Lung Cancer Virtual Congress 2021 (Abstract 203MO).


 

New guidelines prompt study

When the COVID-19 pandemic began, European and joint European and North American guidelines were issued to try to ensure that lung cancer patients would continue to receive the best possible treatment under the circumstances. This included guidance on how and when to use treatments such as radiotherapy.

One U.K. guideline included recommendations on the use of hypofractionation in the COVID-19 era. The recommendations focused on altering the dosage or length of radiotherapy treatments to try to reduce the number of hospital visits, thereby reducing the risk of exposing patients to SARS-CoV-2.

“The aim of these guidelines is very much to reduce the risk to patients,” Dr. Banfill said. “These patients are often at higher risk of serious COVID-19, both as a result of their cancer and also as a result of many of the coexisting medical conditions that they have, such as COPD [chronic obstructive pulmonary disease],” she explained.

The COVID-RT Lung study was essentially born out of these guidelines. The goals of the study were to see what changes to radiotherapy practice occurred as a result of the guidelines and to assess how the changes have affected patient outcomes.
 

Changes to diagnosis and treatment

COVID-RT Lung is an ongoing, prospective study of patients with biopsy- or imaging-proven stage I–III lung cancer who were referred for, or treated with, radical radiotherapy at one of 26 oncology centers in the United Kingdom between April and October 2020.

Records on 1,117 patients were available for the initial analysis. The patients’ median age was 72 years (range, 38-93 years), and half were women.

The records showed changes to diagnostic investigations in 14% of patients (n = 160). Changes included not obtaining histology (4.6%, n = 51), not conducting nodal sampling (3.1%, n = 35), not performing pulmonary function tests (1.8%, n = 20), not conducting brain imaging (2.9%, n = 32), not performing PET/CT scans or having out-of-date scans (4.2%, n = 47), and delays in diagnosis (0.6%, n = 7).

Changes to treatment – deviations from standard care – occurred in 37% of patients (n = 415). This included 19% of patients (n = 210) having changes to radiotherapy dose or fractionation schedule, 8% (n = 86) undergoing radiotherapy instead of surgery, and 13% (n = 143) having their chemotherapy omitted or reduced.

The median number of radiotherapy fractions was 15 for patients who had their radiotherapy adjusted and 20 for those who had no treatment amendments.

“Those who had their treatment changed were more likely to have hypofractionated or ultra-hypofractionated radiotherapy,” Dr. Banfill said.

This was particularly true for patients with early-stage disease, she noted, where there was an increase in the percentage of patients getting more than 15 Gy per fraction. Even in stage III disease, there was an increased use of 3–5 Gy per fraction, although “virtually nobody” who had a change in treatment received less than 2 Gy per fraction, Dr. Banfill said.

“The changes are in line with what was reported in international recommendations,” observed Yolande Lievens, MD, PhD, of Ghent University Hospital in Belgium, who discussed the findings at the meeting.
 

Few patients had COVID-19

“It was striking to me to see that so few patients developed COVID-19 prior to radiotherapy or during radiotherapy,” Dr. Lievens noted. “This is actually something that we’ve also experienced in our setting.”

Indeed, just 15 patients (1%) were diagnosed with COVID-19, 10 of whom were diagnosed before receiving radiotherapy.

Dr. Banfill observed that the COVID-19 diagnosis had been “a reasonable time” before the patients started radiotherapy, and some had been diagnosed with lung cancer as a result of having a chest x-ray for suspected COVID-19.

Of the four patients who were diagnosed during treatment, two had their radiotherapy interrupted as a result.

The low COVID-19 rate is perhaps a result of the protective measures recommended in the United Kingdom, such as advising patients to shield from others, Dr. Banfill said.
 

Are changes to practice likely to hold?

“Part of the reason we actually stopped the data collection in October was that people were starting to go, ‘Well, is this actually a change?’ because they’d been doing it for 6 months,” Dr. Banfill observed during the discussion session.

“It was becoming almost normal for some of these hypofractionated changes. I think there is potential for these to become more embedded going forward,” she said. Data on how these changes might affect patients in the long term is going to be the focus of a future analysis.

“There is ongoing data collection on recurrence and survival and toxicity, which will hopefully provide more information on the outcomes of this patient group,” Dr. Banfill said.

The COVID-RT Lung project is supported by the NIHR Manchester Biomedical Research Centre. Dr. Banfill and Dr. Lievens reported no relevant conflicts of interest.

An increase in the use of hypofractionated radiotherapy for lung cancer has been one of the many consequences of the COVID-19 pandemic, according to initial data from the COVID-RT Lung study.

The U.K.-based study showed that patients with stage I-III lung cancer who were set to undergo radiotherapy with curative intent were more likely to receive fewer fractions at higher doses when treated between April and October 2020. During that period, 19% of patients had their radiotherapy dose or fractionation schedule changed to deviate from standard care.

In addition, 8% of patients who were set to undergo surgery ultimately received radiotherapy instead, presumably to ease pressures on already struggling intensive care services, said Kathryn Banfill, MBChB, of Christie NHS Foundation Trust in Manchester, England.

Dr. Banfill presented results from the COVID-RT Lung study at the European Lung Cancer Virtual Congress 2021 (Abstract 203MO).


 

New guidelines prompt study

When the COVID-19 pandemic began, European and joint European and North American guidelines were issued to try to ensure that lung cancer patients would continue to receive the best possible treatment under the circumstances. This included guidance on how and when to use treatments such as radiotherapy.

One U.K. guideline included recommendations on the use of hypofractionation in the COVID-19 era. The recommendations focused on altering the dosage or length of radiotherapy treatments to try to reduce the number of hospital visits, thereby reducing the risk of exposing patients to SARS-CoV-2.

“The aim of these guidelines is very much to reduce the risk to patients,” Dr. Banfill said. “These patients are often at higher risk of serious COVID-19, both as a result of their cancer and also as a result of many of the coexisting medical conditions that they have, such as COPD [chronic obstructive pulmonary disease],” she explained.

The COVID-RT Lung study was essentially born out of these guidelines. The goals of the study were to see what changes to radiotherapy practice occurred as a result of the guidelines and to assess how the changes have affected patient outcomes.
 

Changes to diagnosis and treatment

COVID-RT Lung is an ongoing, prospective study of patients with biopsy- or imaging-proven stage I–III lung cancer who were referred for, or treated with, radical radiotherapy at one of 26 oncology centers in the United Kingdom between April and October 2020.

Records on 1,117 patients were available for the initial analysis. The patients’ median age was 72 years (range, 38-93 years), and half were women.

The records showed changes to diagnostic investigations in 14% of patients (n = 160). Changes included not obtaining histology (4.6%, n = 51), not conducting nodal sampling (3.1%, n = 35), not performing pulmonary function tests (1.8%, n = 20), not conducting brain imaging (2.9%, n = 32), not performing PET/CT scans or having out-of-date scans (4.2%, n = 47), and delays in diagnosis (0.6%, n = 7).

Changes to treatment – deviations from standard care – occurred in 37% of patients (n = 415). This included 19% of patients (n = 210) having changes to radiotherapy dose or fractionation schedule, 8% (n = 86) undergoing radiotherapy instead of surgery, and 13% (n = 143) having their chemotherapy omitted or reduced.

The median number of radiotherapy fractions was 15 for patients who had their radiotherapy adjusted and 20 for those who had no treatment amendments.

“Those who had their treatment changed were more likely to have hypofractionated or ultra-hypofractionated radiotherapy,” Dr. Banfill said.

This was particularly true for patients with early-stage disease, she noted, where there was an increase in the percentage of patients getting more than 15 Gy per fraction. Even in stage III disease, there was an increased use of 3–5 Gy per fraction, although “virtually nobody” who had a change in treatment received less than 2 Gy per fraction, Dr. Banfill said.

“The changes are in line with what was reported in international recommendations,” observed Yolande Lievens, MD, PhD, of Ghent University Hospital in Belgium, who discussed the findings at the meeting.
 

Few patients had COVID-19

“It was striking to me to see that so few patients developed COVID-19 prior to radiotherapy or during radiotherapy,” Dr. Lievens noted. “This is actually something that we’ve also experienced in our setting.”

Indeed, just 15 patients (1%) were diagnosed with COVID-19, 10 of whom were diagnosed before receiving radiotherapy.

Dr. Banfill observed that the COVID-19 diagnosis had been “a reasonable time” before the patients started radiotherapy, and some had been diagnosed with lung cancer as a result of having a chest x-ray for suspected COVID-19.

Of the four patients who were diagnosed during treatment, two had their radiotherapy interrupted as a result.

The low COVID-19 rate is perhaps a result of the protective measures recommended in the United Kingdom, such as advising patients to shield from others, Dr. Banfill said.
 

Are changes to practice likely to hold?

“Part of the reason we actually stopped the data collection in October was that people were starting to go, ‘Well, is this actually a change?’ because they’d been doing it for 6 months,” Dr. Banfill observed during the discussion session.

“It was becoming almost normal for some of these hypofractionated changes. I think there is potential for these to become more embedded going forward,” she said. Data on how these changes might affect patients in the long term is going to be the focus of a future analysis.

“There is ongoing data collection on recurrence and survival and toxicity, which will hopefully provide more information on the outcomes of this patient group,” Dr. Banfill said.

The COVID-RT Lung project is supported by the NIHR Manchester Biomedical Research Centre. Dr. Banfill and Dr. Lievens reported no relevant conflicts of interest.

A novel technique for pulmonary nodule ablation is feasible and safe for the treatment of early-stage lung cancers, lung metastases, and highly suspicious lung nodules, according to investigators.

The technique – bronchoscopic transbronchial microwave ablation – had a 100% technical success rate and produced low rates of complications in a single-center study.

“We combined the best of both worlds [for this] technique,” said investigator Joyce Chan, MBBS, of Prince of Wales Hospital in Hong Kong, when describing the method at the European Lung Cancer Virtual Congress 2021 (Abstract 64MO).

Dr. Chan explained that microwave ablation of lung nodules is faster and produces larger ablation zones, compared with radiofrequency ablation, and bronchoscopic ablation is thought to produce fewer pleural-based complications than percutaneous ablation.

Bronchoscopic transbronchial microwave ablation is performed in a hybrid operating room. First, the patient is intubated and anesthetized. Then, electromagnetic navigation bronchoscopy is used to zero in on the lung nodule, which is punctured by a microwave catheter. Cone-beam CT is used to confirm the location of the catheter.

“Next, we connect the system externally to a console, and then we just press the button to microwave it, just like what you do to food,” Dr. Chan explained.

Ablation takes about 10 minutes, and another CT is done to assess success. Ground-glass opacities are seen in the ablated area.
 

Study results

Dr. Chan and colleagues performed a retrospective analysis of 36 patients who underwent bronchoscopic transbronchial microwave ablation between March 2019 and December 2020.

The patients were unfit for or unwilling to undergo surgical resection. They had to have stage 1a lung cancers, isolated lung oligometastases, or radiologically suspicious lesions. The nodules had to be less than 3 cm in size, preferably with a bronchus leading directly to the lesion.

The patients had a mean age of 68 years. Their lesions had a mean maximal diameter of 15.2 mm, and 68% were in the peripheral one-third of the lung.

In all, 44 nodules were treated with bronchoscopic transbronchial microwave ablation. The technical success rate was 100%, although eight nodules required double ablation.

The majority of patients (95%) were discharged within 3 days, with 77% discharged on day 1. Complications included mild pain (15.9%), pneumothorax (9.1%), fever/ablation reaction (4.5%), self-limiting hemoptysis (2.3%), and bronchopleural fistula (2.3%).

The ablation zone volume decreased “rapidly” in the first 6-9 months, then leveled off, Dr. Chan noted.

In the 16 nodules with 1 year of follow-up, there were 2 complete responses, 13 partial responses, and no progressions.

It’s too soon to know if the recurrence rate will be lower than the up to 30% recurrence rate with percutaneous microwave ablation, and it’s too soon to know if, without transpleural puncture, the risk of tumor seeding is lower, Dr. Chan said.

“This presentation ... is extremely important,” said invited discussant John Edwards, MBChB, PhD, of Sheffield (England) Teaching Hospitals National Health Service Foundation Trust. “There is a great novelty value in the combination. The complications and the radiologic response rates were quite acceptable.”

The research was funded by the University Grants Committee in Hong Kong. Dr. Chan reported having no disclosures. Her colleagues disclosed relationships with Medtronic, Siemens Healthineers, and Johnson & Johnson. Dr. Edwards disclosed relationships with AstraZeneca, Zimmer Biomet, Stryker Leibinger, Pacific Biosciences, BioNano Genomics, Argenx, and Moderna.

aotto@mdedge.com

A novel technique for pulmonary nodule ablation is feasible and safe for the treatment of early-stage lung cancers, lung metastases, and highly suspicious lung nodules, according to investigators.

The technique – bronchoscopic transbronchial microwave ablation – had a 100% technical success rate and produced low rates of complications in a single-center study.

“We combined the best of both worlds [for this] technique,” said investigator Joyce Chan, MBBS, of Prince of Wales Hospital in Hong Kong, when describing the method at the European Lung Cancer Virtual Congress 2021 (Abstract 64MO).

Dr. Chan explained that microwave ablation of lung nodules is faster and produces larger ablation zones, compared with radiofrequency ablation, and bronchoscopic ablation is thought to produce fewer pleural-based complications than percutaneous ablation.

Bronchoscopic transbronchial microwave ablation is performed in a hybrid operating room. First, the patient is intubated and anesthetized. Then, electromagnetic navigation bronchoscopy is used to zero in on the lung nodule, which is punctured by a microwave catheter. Cone-beam CT is used to confirm the location of the catheter.

“Next, we connect the system externally to a console, and then we just press the button to microwave it, just like what you do to food,” Dr. Chan explained.

Ablation takes about 10 minutes, and another CT is done to assess success. Ground-glass opacities are seen in the ablated area.
 

Study results

Dr. Chan and colleagues performed a retrospective analysis of 36 patients who underwent bronchoscopic transbronchial microwave ablation between March 2019 and December 2020.

The patients were unfit for or unwilling to undergo surgical resection. They had to have stage 1a lung cancers, isolated lung oligometastases, or radiologically suspicious lesions. The nodules had to be less than 3 cm in size, preferably with a bronchus leading directly to the lesion.

The patients had a mean age of 68 years. Their lesions had a mean maximal diameter of 15.2 mm, and 68% were in the peripheral one-third of the lung.

In all, 44 nodules were treated with bronchoscopic transbronchial microwave ablation. The technical success rate was 100%, although eight nodules required double ablation.

The majority of patients (95%) were discharged within 3 days, with 77% discharged on day 1. Complications included mild pain (15.9%), pneumothorax (9.1%), fever/ablation reaction (4.5%), self-limiting hemoptysis (2.3%), and bronchopleural fistula (2.3%).

The ablation zone volume decreased “rapidly” in the first 6-9 months, then leveled off, Dr. Chan noted.

In the 16 nodules with 1 year of follow-up, there were 2 complete responses, 13 partial responses, and no progressions.

It’s too soon to know if the recurrence rate will be lower than the up to 30% recurrence rate with percutaneous microwave ablation, and it’s too soon to know if, without transpleural puncture, the risk of tumor seeding is lower, Dr. Chan said.

“This presentation ... is extremely important,” said invited discussant John Edwards, MBChB, PhD, of Sheffield (England) Teaching Hospitals National Health Service Foundation Trust. “There is a great novelty value in the combination. The complications and the radiologic response rates were quite acceptable.”

The research was funded by the University Grants Committee in Hong Kong. Dr. Chan reported having no disclosures. Her colleagues disclosed relationships with Medtronic, Siemens Healthineers, and Johnson & Johnson. Dr. Edwards disclosed relationships with AstraZeneca, Zimmer Biomet, Stryker Leibinger, Pacific Biosciences, BioNano Genomics, Argenx, and Moderna.

aotto@mdedge.com

A novel technique for pulmonary nodule ablation is feasible and safe for the treatment of early-stage lung cancers, lung metastases, and highly suspicious lung nodules, according to investigators.

The technique – bronchoscopic transbronchial microwave ablation – had a 100% technical success rate and produced low rates of complications in a single-center study.

“We combined the best of both worlds [for this] technique,” said investigator Joyce Chan, MBBS, of Prince of Wales Hospital in Hong Kong, when describing the method at the European Lung Cancer Virtual Congress 2021 (Abstract 64MO).

Dr. Chan explained that microwave ablation of lung nodules is faster and produces larger ablation zones, compared with radiofrequency ablation, and bronchoscopic ablation is thought to produce fewer pleural-based complications than percutaneous ablation.

Bronchoscopic transbronchial microwave ablation is performed in a hybrid operating room. First, the patient is intubated and anesthetized. Then, electromagnetic navigation bronchoscopy is used to zero in on the lung nodule, which is punctured by a microwave catheter. Cone-beam CT is used to confirm the location of the catheter.

“Next, we connect the system externally to a console, and then we just press the button to microwave it, just like what you do to food,” Dr. Chan explained.

Ablation takes about 10 minutes, and another CT is done to assess success. Ground-glass opacities are seen in the ablated area.
 

Study results

Dr. Chan and colleagues performed a retrospective analysis of 36 patients who underwent bronchoscopic transbronchial microwave ablation between March 2019 and December 2020.

The patients were unfit for or unwilling to undergo surgical resection. They had to have stage 1a lung cancers, isolated lung oligometastases, or radiologically suspicious lesions. The nodules had to be less than 3 cm in size, preferably with a bronchus leading directly to the lesion.

The patients had a mean age of 68 years. Their lesions had a mean maximal diameter of 15.2 mm, and 68% were in the peripheral one-third of the lung.

In all, 44 nodules were treated with bronchoscopic transbronchial microwave ablation. The technical success rate was 100%, although eight nodules required double ablation.

The majority of patients (95%) were discharged within 3 days, with 77% discharged on day 1. Complications included mild pain (15.9%), pneumothorax (9.1%), fever/ablation reaction (4.5%), self-limiting hemoptysis (2.3%), and bronchopleural fistula (2.3%).

The ablation zone volume decreased “rapidly” in the first 6-9 months, then leveled off, Dr. Chan noted.

In the 16 nodules with 1 year of follow-up, there were 2 complete responses, 13 partial responses, and no progressions.

It’s too soon to know if the recurrence rate will be lower than the up to 30% recurrence rate with percutaneous microwave ablation, and it’s too soon to know if, without transpleural puncture, the risk of tumor seeding is lower, Dr. Chan said.

“This presentation ... is extremely important,” said invited discussant John Edwards, MBChB, PhD, of Sheffield (England) Teaching Hospitals National Health Service Foundation Trust. “There is a great novelty value in the combination. The complications and the radiologic response rates were quite acceptable.”

The research was funded by the University Grants Committee in Hong Kong. Dr. Chan reported having no disclosures. Her colleagues disclosed relationships with Medtronic, Siemens Healthineers, and Johnson & Johnson. Dr. Edwards disclosed relationships with AstraZeneca, Zimmer Biomet, Stryker Leibinger, Pacific Biosciences, BioNano Genomics, Argenx, and Moderna.

aotto@mdedge.com

Significant survival gains were seen when the immune checkpoint inhibitor camrelizumab was added to standard chemotherapy for the first-line treatment of advanced squamous non–small cell lung cancer (NSCLC) in a phase 3 trial conducted in China.

Results of the CAMEL-sq trial showed a progression-free survival (PFS) advantage of 3.6 months with camrelizumab plus chemotherapy, compared with chemotherapy plus placebo (P < .0001). The median overall survival (OS) was not reached in the camrelizumab arm, but it was significantly better than in the placebo arm (P < .0001).

Camrelizumab plus chemotherapy is already a standard of care in China for patients with advanced nonsquamous NSCLC who are negative for EGFR and ALK mutations, study investigator Caicun Zhou, MD, PhD, said when presenting the CAMEL-sq results at the European Lung Cancer Virtual Congress 2021 (Abstract 96O).

The CAMEL-sq findings now support the combination as a “standard first-line treatment for advanced squamous NSCLC,” said Dr. Zhou of Shanghai Pulmonary Hospital and Tongji University.

“The study has kind of changed our daily practice,” he said. “I do think we will have the label, camrelizumab plus chemo as first-line treatment for squamous [NSCLC] in China, maybe in a couple of months.”

“Camrelizumab will most likely be another brick in the wall for our Chinese patients and colleagues to use for patients with squamous histology, non–small cell lung cancer in addition to pembrolizumab,” said Julie Renee Brahmer, MD, of Johns Hopkins Medicine in Baltimore, who was the invited discussant for the trial.

Dr. Brahmer noted that the PFS hazard ratio in this trial – 0.37 – was “impressive.”
 

Patients and treatment

CAMEL-sq is a phase 3, double-blind, multicenter trial. The 390 patients enrolled had pathologically-confirmed stage IIIB or IV squamous NSCLC, and they had not received any prior treatment.

Patients received four to six cycles of chemotherapy, consisting of carboplatin and paclitaxel given every 3 weeks. Camrelizumab was added to one arm at a dose of 200 mg, and placebo was added to the other.

This was followed by a maintenance phase in which patients remained on active treatment with camrelizumab or placebo for up to 2 years. Patients in the placebo arm could cross over to camrelizumab at progression.

The median age of patients was similar in the camrelizumab and placebo arms (64 years and 62 years, respectively). The majority of study subjects in both arms were men (more than 90%), had a history of smoking (more than 80%), and had stage IV disease (more than 70%).
 

Efficacy and safety

The median PFS was 8.5 months in the camrelizumab arm and 4.9 months in the placebo arm (HR, 0.37; P < .0001). The median OS was not reached in the camrelizumab arm and was 14.5 months in the placebo arm (HR, 0.55, P < .0001).

The survival benefits were observed in spite of a crossover rate of 46.9%, Dr. Zhou noted.

Furthermore, survival benefits were consistent across all the subgroups tested. Regardless of age, sex, performance status, smoking history, disease stage, presence of liver or brain metastases, or PD-L1 expression, there was an apparent advantage of camrelizumab over placebo.

The objective response rate was higher in the camrelizumab arm than in the placebo arm, at 64.8% and 36.7%, respectively (P < .0001).

The clinical response seen with camrelizumab was “robust and durable,” Dr. Zhou said. Indeed, the duration of response was 13.1 months in the camrelizumab arm and 4.4 months in the placebo arm.

Grade 3/4 treatment-related adverse events (AEs) were reported in a similar percentage of camrelizumab- or placebo-treated patients (73.6% and 71.4%, respectively). However, “the majority of treatment-related adverse effects were chemotherapy related,” Dr. Zhou pointed out. This included decreased total white blood cell, neutrophil, red blood cell, and platelet counts as well as alopecia and increased liver enzymes.

Immune-related AEs occurred in 76.7% of patients in the camrelizumab arm and 20.4% of those in the placebo arm.

“The majority of immune-related adverse events were grade 1 or grade 2; easily manageable in our daily practice,” Dr. Zhou noted.
 

Putting CAMEL-sq into perspective

Data from other trials of immunotherapy-chemotherapy combinations in squamous NSCLC have been presented recently but with less impressive results, Dr. Brahmer said.

In one trial – ORIENT-12 – sintilimab was combined with gemcitabine and cisplatin (ESMO 2020, Abstract LBA56). The median PFS, per investigators, was 5.5 months with sintilimab and 4.9 months without it, both of which are lower than the 8.5 months seen with camrelizumab plus chemotherapy in the CAMEL-sq trial.

Another trial is KEYNOTE-407, in which patients received pembrolizumab or placebo plus a carboplatin-paclitaxel (or nab-paclitaxel) regimen. Three-year follow-up data from the trial were presented at ELCC 2021 (Abstract 97O). Continued improvements in second PFS (HR, 0.59) and OS (HR, 0.71) were observed with pembrolizumab-chemotherapy versus placebo-chemotherapy.

“We have to remember the high PD-L1-negative disease rate in the CAMEL-sq study, compared to the KEYNOTE-407 rate,” before stacking the two studies against each other, Dr. Brahmer noted. In KEYNOTE-407, almost 35% of patients had PD-L1 expression of less than 1%, compared with nearly 50% in the CAMEL-sq study.

That aside, “very similar impressive 1-year progression-free survival rates are seen on both studies,” Dr. Brahmer said. “I hope that camrelizumab has continued follow-up so we can see how these patients will do long-term.

“My eyebrows were raised a little bit at the camrelizumab immune-related AE rate of almost 76%, compared to the immune-related AE rate of about 36% in the KEYNOTE-407 study,” Dr. Brahmer said.

She noted, however, that almost two-thirds of the immune-related AEs in CAMEL-sq were due to reactive cutaneous capillary endothelial proliferation, which doesn’t appear to have been previously reported with PD-1 or PD-L1 inhibitors. This is a side effect seen in studies of liver cancer and may be linked to PFS, Dr. Brahmer said.

CAMEL-sq is funded by Jiangsu Hengrui Medicine Co. Ltd. Dr. Zhou disclosed honoraria from multiple pharmaceutical companies, including the study sponsor. Two of Dr. Zhou’s coauthors are employees of the company. Dr. Brahmer disclosed relationships with Amgen, Bristol Myers Squibb, Eli Lily, GlaxoSmithKline, Merck, Sanofi, Easi, AstraZeneca, Genentech, Regeneron, and RAPT Therapeutics Inc.

Significant survival gains were seen when the immune checkpoint inhibitor camrelizumab was added to standard chemotherapy for the first-line treatment of advanced squamous non–small cell lung cancer (NSCLC) in a phase 3 trial conducted in China.

Results of the CAMEL-sq trial showed a progression-free survival (PFS) advantage of 3.6 months with camrelizumab plus chemotherapy, compared with chemotherapy plus placebo (P < .0001). The median overall survival (OS) was not reached in the camrelizumab arm, but it was significantly better than in the placebo arm (P < .0001).

Camrelizumab plus chemotherapy is already a standard of care in China for patients with advanced nonsquamous NSCLC who are negative for EGFR and ALK mutations, study investigator Caicun Zhou, MD, PhD, said when presenting the CAMEL-sq results at the European Lung Cancer Virtual Congress 2021 (Abstract 96O).

The CAMEL-sq findings now support the combination as a “standard first-line treatment for advanced squamous NSCLC,” said Dr. Zhou of Shanghai Pulmonary Hospital and Tongji University.

“The study has kind of changed our daily practice,” he said. “I do think we will have the label, camrelizumab plus chemo as first-line treatment for squamous [NSCLC] in China, maybe in a couple of months.”

“Camrelizumab will most likely be another brick in the wall for our Chinese patients and colleagues to use for patients with squamous histology, non–small cell lung cancer in addition to pembrolizumab,” said Julie Renee Brahmer, MD, of Johns Hopkins Medicine in Baltimore, who was the invited discussant for the trial.

Dr. Brahmer noted that the PFS hazard ratio in this trial – 0.37 – was “impressive.”
 

Patients and treatment

CAMEL-sq is a phase 3, double-blind, multicenter trial. The 390 patients enrolled had pathologically-confirmed stage IIIB or IV squamous NSCLC, and they had not received any prior treatment.

Patients received four to six cycles of chemotherapy, consisting of carboplatin and paclitaxel given every 3 weeks. Camrelizumab was added to one arm at a dose of 200 mg, and placebo was added to the other.

This was followed by a maintenance phase in which patients remained on active treatment with camrelizumab or placebo for up to 2 years. Patients in the placebo arm could cross over to camrelizumab at progression.

The median age of patients was similar in the camrelizumab and placebo arms (64 years and 62 years, respectively). The majority of study subjects in both arms were men (more than 90%), had a history of smoking (more than 80%), and had stage IV disease (more than 70%).
 

Efficacy and safety

The median PFS was 8.5 months in the camrelizumab arm and 4.9 months in the placebo arm (HR, 0.37; P < .0001). The median OS was not reached in the camrelizumab arm and was 14.5 months in the placebo arm (HR, 0.55, P < .0001).

The survival benefits were observed in spite of a crossover rate of 46.9%, Dr. Zhou noted.

Furthermore, survival benefits were consistent across all the subgroups tested. Regardless of age, sex, performance status, smoking history, disease stage, presence of liver or brain metastases, or PD-L1 expression, there was an apparent advantage of camrelizumab over placebo.

The objective response rate was higher in the camrelizumab arm than in the placebo arm, at 64.8% and 36.7%, respectively (P < .0001).

The clinical response seen with camrelizumab was “robust and durable,” Dr. Zhou said. Indeed, the duration of response was 13.1 months in the camrelizumab arm and 4.4 months in the placebo arm.

Grade 3/4 treatment-related adverse events (AEs) were reported in a similar percentage of camrelizumab- or placebo-treated patients (73.6% and 71.4%, respectively). However, “the majority of treatment-related adverse effects were chemotherapy related,” Dr. Zhou pointed out. This included decreased total white blood cell, neutrophil, red blood cell, and platelet counts as well as alopecia and increased liver enzymes.

Immune-related AEs occurred in 76.7% of patients in the camrelizumab arm and 20.4% of those in the placebo arm.

“The majority of immune-related adverse events were grade 1 or grade 2; easily manageable in our daily practice,” Dr. Zhou noted.
 

Putting CAMEL-sq into perspective

Data from other trials of immunotherapy-chemotherapy combinations in squamous NSCLC have been presented recently but with less impressive results, Dr. Brahmer said.

In one trial – ORIENT-12 – sintilimab was combined with gemcitabine and cisplatin (ESMO 2020, Abstract LBA56). The median PFS, per investigators, was 5.5 months with sintilimab and 4.9 months without it, both of which are lower than the 8.5 months seen with camrelizumab plus chemotherapy in the CAMEL-sq trial.

Another trial is KEYNOTE-407, in which patients received pembrolizumab or placebo plus a carboplatin-paclitaxel (or nab-paclitaxel) regimen. Three-year follow-up data from the trial were presented at ELCC 2021 (Abstract 97O). Continued improvements in second PFS (HR, 0.59) and OS (HR, 0.71) were observed with pembrolizumab-chemotherapy versus placebo-chemotherapy.

“We have to remember the high PD-L1-negative disease rate in the CAMEL-sq study, compared to the KEYNOTE-407 rate,” before stacking the two studies against each other, Dr. Brahmer noted. In KEYNOTE-407, almost 35% of patients had PD-L1 expression of less than 1%, compared with nearly 50% in the CAMEL-sq study.

That aside, “very similar impressive 1-year progression-free survival rates are seen on both studies,” Dr. Brahmer said. “I hope that camrelizumab has continued follow-up so we can see how these patients will do long-term.

“My eyebrows were raised a little bit at the camrelizumab immune-related AE rate of almost 76%, compared to the immune-related AE rate of about 36% in the KEYNOTE-407 study,” Dr. Brahmer said.

She noted, however, that almost two-thirds of the immune-related AEs in CAMEL-sq were due to reactive cutaneous capillary endothelial proliferation, which doesn’t appear to have been previously reported with PD-1 or PD-L1 inhibitors. This is a side effect seen in studies of liver cancer and may be linked to PFS, Dr. Brahmer said.

CAMEL-sq is funded by Jiangsu Hengrui Medicine Co. Ltd. Dr. Zhou disclosed honoraria from multiple pharmaceutical companies, including the study sponsor. Two of Dr. Zhou’s coauthors are employees of the company. Dr. Brahmer disclosed relationships with Amgen, Bristol Myers Squibb, Eli Lily, GlaxoSmithKline, Merck, Sanofi, Easi, AstraZeneca, Genentech, Regeneron, and RAPT Therapeutics Inc.

Significant survival gains were seen when the immune checkpoint inhibitor camrelizumab was added to standard chemotherapy for the first-line treatment of advanced squamous non–small cell lung cancer (NSCLC) in a phase 3 trial conducted in China.

Results of the CAMEL-sq trial showed a progression-free survival (PFS) advantage of 3.6 months with camrelizumab plus chemotherapy, compared with chemotherapy plus placebo (P < .0001). The median overall survival (OS) was not reached in the camrelizumab arm, but it was significantly better than in the placebo arm (P < .0001).

Camrelizumab plus chemotherapy is already a standard of care in China for patients with advanced nonsquamous NSCLC who are negative for EGFR and ALK mutations, study investigator Caicun Zhou, MD, PhD, said when presenting the CAMEL-sq results at the European Lung Cancer Virtual Congress 2021 (Abstract 96O).

The CAMEL-sq findings now support the combination as a “standard first-line treatment for advanced squamous NSCLC,” said Dr. Zhou of Shanghai Pulmonary Hospital and Tongji University.

“The study has kind of changed our daily practice,” he said. “I do think we will have the label, camrelizumab plus chemo as first-line treatment for squamous [NSCLC] in China, maybe in a couple of months.”

“Camrelizumab will most likely be another brick in the wall for our Chinese patients and colleagues to use for patients with squamous histology, non–small cell lung cancer in addition to pembrolizumab,” said Julie Renee Brahmer, MD, of Johns Hopkins Medicine in Baltimore, who was the invited discussant for the trial.

Dr. Brahmer noted that the PFS hazard ratio in this trial – 0.37 – was “impressive.”
 

Patients and treatment

CAMEL-sq is a phase 3, double-blind, multicenter trial. The 390 patients enrolled had pathologically-confirmed stage IIIB or IV squamous NSCLC, and they had not received any prior treatment.

Patients received four to six cycles of chemotherapy, consisting of carboplatin and paclitaxel given every 3 weeks. Camrelizumab was added to one arm at a dose of 200 mg, and placebo was added to the other.

This was followed by a maintenance phase in which patients remained on active treatment with camrelizumab or placebo for up to 2 years. Patients in the placebo arm could cross over to camrelizumab at progression.

The median age of patients was similar in the camrelizumab and placebo arms (64 years and 62 years, respectively). The majority of study subjects in both arms were men (more than 90%), had a history of smoking (more than 80%), and had stage IV disease (more than 70%).
 

Efficacy and safety

The median PFS was 8.5 months in the camrelizumab arm and 4.9 months in the placebo arm (HR, 0.37; P < .0001). The median OS was not reached in the camrelizumab arm and was 14.5 months in the placebo arm (HR, 0.55, P < .0001).

The survival benefits were observed in spite of a crossover rate of 46.9%, Dr. Zhou noted.

Furthermore, survival benefits were consistent across all the subgroups tested. Regardless of age, sex, performance status, smoking history, disease stage, presence of liver or brain metastases, or PD-L1 expression, there was an apparent advantage of camrelizumab over placebo.

The objective response rate was higher in the camrelizumab arm than in the placebo arm, at 64.8% and 36.7%, respectively (P < .0001).

The clinical response seen with camrelizumab was “robust and durable,” Dr. Zhou said. Indeed, the duration of response was 13.1 months in the camrelizumab arm and 4.4 months in the placebo arm.

Grade 3/4 treatment-related adverse events (AEs) were reported in a similar percentage of camrelizumab- or placebo-treated patients (73.6% and 71.4%, respectively). However, “the majority of treatment-related adverse effects were chemotherapy related,” Dr. Zhou pointed out. This included decreased total white blood cell, neutrophil, red blood cell, and platelet counts as well as alopecia and increased liver enzymes.

Immune-related AEs occurred in 76.7% of patients in the camrelizumab arm and 20.4% of those in the placebo arm.

“The majority of immune-related adverse events were grade 1 or grade 2; easily manageable in our daily practice,” Dr. Zhou noted.
 

Putting CAMEL-sq into perspective

Data from other trials of immunotherapy-chemotherapy combinations in squamous NSCLC have been presented recently but with less impressive results, Dr. Brahmer said.

In one trial – ORIENT-12 – sintilimab was combined with gemcitabine and cisplatin (ESMO 2020, Abstract LBA56). The median PFS, per investigators, was 5.5 months with sintilimab and 4.9 months without it, both of which are lower than the 8.5 months seen with camrelizumab plus chemotherapy in the CAMEL-sq trial.

Another trial is KEYNOTE-407, in which patients received pembrolizumab or placebo plus a carboplatin-paclitaxel (or nab-paclitaxel) regimen. Three-year follow-up data from the trial were presented at ELCC 2021 (Abstract 97O). Continued improvements in second PFS (HR, 0.59) and OS (HR, 0.71) were observed with pembrolizumab-chemotherapy versus placebo-chemotherapy.

“We have to remember the high PD-L1-negative disease rate in the CAMEL-sq study, compared to the KEYNOTE-407 rate,” before stacking the two studies against each other, Dr. Brahmer noted. In KEYNOTE-407, almost 35% of patients had PD-L1 expression of less than 1%, compared with nearly 50% in the CAMEL-sq study.

That aside, “very similar impressive 1-year progression-free survival rates are seen on both studies,” Dr. Brahmer said. “I hope that camrelizumab has continued follow-up so we can see how these patients will do long-term.

“My eyebrows were raised a little bit at the camrelizumab immune-related AE rate of almost 76%, compared to the immune-related AE rate of about 36% in the KEYNOTE-407 study,” Dr. Brahmer said.

She noted, however, that almost two-thirds of the immune-related AEs in CAMEL-sq were due to reactive cutaneous capillary endothelial proliferation, which doesn’t appear to have been previously reported with PD-1 or PD-L1 inhibitors. This is a side effect seen in studies of liver cancer and may be linked to PFS, Dr. Brahmer said.

CAMEL-sq is funded by Jiangsu Hengrui Medicine Co. Ltd. Dr. Zhou disclosed honoraria from multiple pharmaceutical companies, including the study sponsor. Two of Dr. Zhou’s coauthors are employees of the company. Dr. Brahmer disclosed relationships with Amgen, Bristol Myers Squibb, Eli Lily, GlaxoSmithKline, Merck, Sanofi, Easi, AstraZeneca, Genentech, Regeneron, and RAPT Therapeutics Inc.

Stereotactic body radiotherapy (SBRT) produced high disease control rates but serious toxicity in a retrospective study of patients with ultra-central lung tumors.

Of the 72 patients studied, 15 (21%) experienced grade 3 or higher toxicity and 10 (14%) died of bronchopulmonary hemorrhage.

This doesn’t completely write off the use of SBRT for ultra-central lung tumors, according to Joyce Lodeweges, MD, of University Medical Center (UMC) Utrecht in the Netherlands.

“We have to inform the patient very well that there are some high risks to this treatment,” she said at the European Lung Cancer Virtual Congress 2021 (Abstract 61M0).

Dr. Lodeweges noted that keeping the biologically effective dose of radiation to the main bronchus below a certain threshold (< 90 Gy) could reduce the risk of toxicity significantly, making SBRT a viable option for some patients. In addition, MRI-guided daily adaptation of the radiation treatment to organs at risk may make the treatment safer.
 

Varying definitions, regimens spur debate

SBRT is standard care in peripherally located, stage I non–small cell lung cancer that is inoperable or if the patient refuses surgery, noted study discussant Yolande Lievens, MD, PhD, of Ghent University Hospital in Belgium.

“[SBRT] has good local control rates with low toxicity even in patients with COPD or being elderly,” Dr. Lievens said.

“In more moderately central tumors, there is quite some evidence that risk-adapted fractionation schemes can be delivered in a safe way and lead to high local control rates,” she added. “For ultra-central legions, there’s still not a recommendation to treat with SBRT because we see a lot of increased toxicity.”

“For ultra-central tumors, SBRT is still under debate,” agreed Dr. Lodeweges. “This is because of the varying definitions in the literature and the varying fractionation schemes used.”

How the location of tumors is defined is important. Central tumors are those that are at least 2 cm away from the main bronchial tree, whereas ultra-central tumors are those that butt onto it or overlap it.

In Dr. Lodeweges’s study, ultra-central tumors were defined as those with a planning target volume (PTV) abutting or overlapping the main bronchi, trachea, and/or esophagus.
 

Study details

Between 2012 and 2020, there were 72 patients with ultra-central lung tumors treated at UMC Utrecht. Most patients (78%) had a PTV covering the main bronchus, with 21% each having PTVs overlapping the trachea or esophagus.

Patients received a protracted SBRT regimen of 60 Gy given in 12 fractions. The median follow-up was 19 months.

The local failure-free survival rate was 98% at 1 year and 85% at 2 years. Overall survival rates were 77% and 52%, respectively.

Receiving a biologically effective dose of more than 90 Gy to the main bronchus increased the risk of grade 3 or higher toxicity. On the other hand, patient age and tumor histology did not affect the risk of adverse events.

The use of antithrombotic therapy didn’t have any bearing on toxicity either, but it’s a possible risk factor to consider, Dr. Lodeweges said. Peri- or endobronchial tumor location is another consideration.
 

Findings in context

How do the results of the current study sit with other studies of SBRT in non–small cell lung cancer? Dr. Lievens pointed out that overall survival at 2 years was lower in the current trial (52%) than in patients with central tumors treated in the RTOG 0813 trial (68%-73%) or those with peripheral tumors in the CHISEL trial (77%).

There were, of course, different fractions and doses of radiotherapy used in these trials, with lower doses and more fractions in the UMC Utrecht study, and there was higher toxicity when ultra-central lesions were treated.

“Optimized radiotherapy dose fractionation regimens are investigated quite intensively to improve the clinical benefit. This is an important area of research,” Dr. Lievens said.

The high local control rates but serious risk of bronchopulmonary hemorrhage seen in the current study “calls for further investigation of dose/volume parameters in the context of the location of the tumor but also in the context of other treatment modalities,” she added. “Advanced technologies in radiotherapy, which allow better imaging and daily adaptation, such as the MR-Linac, can optimize clinical benefits.”

The study was supported by UMC Utrecht and received no commercial funding. Dr. Lodeweges and Dr. Lievens had no relevant conflicts of interest.

Stereotactic body radiotherapy (SBRT) produced high disease control rates but serious toxicity in a retrospective study of patients with ultra-central lung tumors.

Of the 72 patients studied, 15 (21%) experienced grade 3 or higher toxicity and 10 (14%) died of bronchopulmonary hemorrhage.

This doesn’t completely write off the use of SBRT for ultra-central lung tumors, according to Joyce Lodeweges, MD, of University Medical Center (UMC) Utrecht in the Netherlands.

“We have to inform the patient very well that there are some high risks to this treatment,” she said at the European Lung Cancer Virtual Congress 2021 (Abstract 61M0).

Dr. Lodeweges noted that keeping the biologically effective dose of radiation to the main bronchus below a certain threshold (< 90 Gy) could reduce the risk of toxicity significantly, making SBRT a viable option for some patients. In addition, MRI-guided daily adaptation of the radiation treatment to organs at risk may make the treatment safer.
 

Varying definitions, regimens spur debate

SBRT is standard care in peripherally located, stage I non–small cell lung cancer that is inoperable or if the patient refuses surgery, noted study discussant Yolande Lievens, MD, PhD, of Ghent University Hospital in Belgium.

“[SBRT] has good local control rates with low toxicity even in patients with COPD or being elderly,” Dr. Lievens said.

“In more moderately central tumors, there is quite some evidence that risk-adapted fractionation schemes can be delivered in a safe way and lead to high local control rates,” she added. “For ultra-central legions, there’s still not a recommendation to treat with SBRT because we see a lot of increased toxicity.”

“For ultra-central tumors, SBRT is still under debate,” agreed Dr. Lodeweges. “This is because of the varying definitions in the literature and the varying fractionation schemes used.”

How the location of tumors is defined is important. Central tumors are those that are at least 2 cm away from the main bronchial tree, whereas ultra-central tumors are those that butt onto it or overlap it.

In Dr. Lodeweges’s study, ultra-central tumors were defined as those with a planning target volume (PTV) abutting or overlapping the main bronchi, trachea, and/or esophagus.
 

Study details

Between 2012 and 2020, there were 72 patients with ultra-central lung tumors treated at UMC Utrecht. Most patients (78%) had a PTV covering the main bronchus, with 21% each having PTVs overlapping the trachea or esophagus.

Patients received a protracted SBRT regimen of 60 Gy given in 12 fractions. The median follow-up was 19 months.

The local failure-free survival rate was 98% at 1 year and 85% at 2 years. Overall survival rates were 77% and 52%, respectively.

Receiving a biologically effective dose of more than 90 Gy to the main bronchus increased the risk of grade 3 or higher toxicity. On the other hand, patient age and tumor histology did not affect the risk of adverse events.

The use of antithrombotic therapy didn’t have any bearing on toxicity either, but it’s a possible risk factor to consider, Dr. Lodeweges said. Peri- or endobronchial tumor location is another consideration.
 

Findings in context

How do the results of the current study sit with other studies of SBRT in non–small cell lung cancer? Dr. Lievens pointed out that overall survival at 2 years was lower in the current trial (52%) than in patients with central tumors treated in the RTOG 0813 trial (68%-73%) or those with peripheral tumors in the CHISEL trial (77%).

There were, of course, different fractions and doses of radiotherapy used in these trials, with lower doses and more fractions in the UMC Utrecht study, and there was higher toxicity when ultra-central lesions were treated.

“Optimized radiotherapy dose fractionation regimens are investigated quite intensively to improve the clinical benefit. This is an important area of research,” Dr. Lievens said.

The high local control rates but serious risk of bronchopulmonary hemorrhage seen in the current study “calls for further investigation of dose/volume parameters in the context of the location of the tumor but also in the context of other treatment modalities,” she added. “Advanced technologies in radiotherapy, which allow better imaging and daily adaptation, such as the MR-Linac, can optimize clinical benefits.”

The study was supported by UMC Utrecht and received no commercial funding. Dr. Lodeweges and Dr. Lievens had no relevant conflicts of interest.

Stereotactic body radiotherapy (SBRT) produced high disease control rates but serious toxicity in a retrospective study of patients with ultra-central lung tumors.

Of the 72 patients studied, 15 (21%) experienced grade 3 or higher toxicity and 10 (14%) died of bronchopulmonary hemorrhage.

This doesn’t completely write off the use of SBRT for ultra-central lung tumors, according to Joyce Lodeweges, MD, of University Medical Center (UMC) Utrecht in the Netherlands.

“We have to inform the patient very well that there are some high risks to this treatment,” she said at the European Lung Cancer Virtual Congress 2021 (Abstract 61M0).

Dr. Lodeweges noted that keeping the biologically effective dose of radiation to the main bronchus below a certain threshold (< 90 Gy) could reduce the risk of toxicity significantly, making SBRT a viable option for some patients. In addition, MRI-guided daily adaptation of the radiation treatment to organs at risk may make the treatment safer.
 

Varying definitions, regimens spur debate

SBRT is standard care in peripherally located, stage I non–small cell lung cancer that is inoperable or if the patient refuses surgery, noted study discussant Yolande Lievens, MD, PhD, of Ghent University Hospital in Belgium.

“[SBRT] has good local control rates with low toxicity even in patients with COPD or being elderly,” Dr. Lievens said.

“In more moderately central tumors, there is quite some evidence that risk-adapted fractionation schemes can be delivered in a safe way and lead to high local control rates,” she added. “For ultra-central legions, there’s still not a recommendation to treat with SBRT because we see a lot of increased toxicity.”

“For ultra-central tumors, SBRT is still under debate,” agreed Dr. Lodeweges. “This is because of the varying definitions in the literature and the varying fractionation schemes used.”

How the location of tumors is defined is important. Central tumors are those that are at least 2 cm away from the main bronchial tree, whereas ultra-central tumors are those that butt onto it or overlap it.

In Dr. Lodeweges’s study, ultra-central tumors were defined as those with a planning target volume (PTV) abutting or overlapping the main bronchi, trachea, and/or esophagus.
 

Study details

Between 2012 and 2020, there were 72 patients with ultra-central lung tumors treated at UMC Utrecht. Most patients (78%) had a PTV covering the main bronchus, with 21% each having PTVs overlapping the trachea or esophagus.

Patients received a protracted SBRT regimen of 60 Gy given in 12 fractions. The median follow-up was 19 months.

The local failure-free survival rate was 98% at 1 year and 85% at 2 years. Overall survival rates were 77% and 52%, respectively.

Receiving a biologically effective dose of more than 90 Gy to the main bronchus increased the risk of grade 3 or higher toxicity. On the other hand, patient age and tumor histology did not affect the risk of adverse events.

The use of antithrombotic therapy didn’t have any bearing on toxicity either, but it’s a possible risk factor to consider, Dr. Lodeweges said. Peri- or endobronchial tumor location is another consideration.
 

Findings in context

How do the results of the current study sit with other studies of SBRT in non–small cell lung cancer? Dr. Lievens pointed out that overall survival at 2 years was lower in the current trial (52%) than in patients with central tumors treated in the RTOG 0813 trial (68%-73%) or those with peripheral tumors in the CHISEL trial (77%).

There were, of course, different fractions and doses of radiotherapy used in these trials, with lower doses and more fractions in the UMC Utrecht study, and there was higher toxicity when ultra-central lesions were treated.

“Optimized radiotherapy dose fractionation regimens are investigated quite intensively to improve the clinical benefit. This is an important area of research,” Dr. Lievens said.

The high local control rates but serious risk of bronchopulmonary hemorrhage seen in the current study “calls for further investigation of dose/volume parameters in the context of the location of the tumor but also in the context of other treatment modalities,” she added. “Advanced technologies in radiotherapy, which allow better imaging and daily adaptation, such as the MR-Linac, can optimize clinical benefits.”

The study was supported by UMC Utrecht and received no commercial funding. Dr. Lodeweges and Dr. Lievens had no relevant conflicts of interest.

The KRAS inhibitor adagrasib produced a high disease control rate in patients with advanced or metastatic non–small cell lung cancer (NSCLC), according to data from the KRYSTAL-1 study.

An objective response rate was seen in 45% of patients, with a further 51% achieving stable disease, for a disease control rate of 96%.

“The vast majority of patients had significant tumor shrinkage,” said study investigator Gregory J. Riely, MD, PhD, when presenting the results at the European Lung Cancer Virtual Congress 2021 (Abstract 990_PR).

Dr. Riely, vice chair of clinical research in the department of medicine at Memorial Sloan Kettering Cancer Center in New York, noted that just 6 of the 70 patients in this phase 1/2 trial showed evidence of measurable tumor growth.

“This new way of targeting an oncogene may very well represent an evolutionary step forward in the management of lung cancer patients, akin to when we first had EGFR inhibitors,” Alastair Greystoke, MBChB, PhD, said in his discussion of the trial.

Dr. Greystoke, a clinical senior lecturer and honorary consultant in medical oncology at Newcastle (England) University, observed that the availability of KRAS-targeting agents could have a large potential impact on clinical practice. They could add another 14% of patients with NSCLC to the list of those who are eligible for molecularly-targeted therapy.

“It may be that soon, almost half our patients with lung adenocarcinoma will have a potential targetable abnormality,” Dr. Greystoke said.
 

Data confirm KRAS as a therapeutic target

Adagrasib is now the second drug to show promise as an inhibitor of KRAS G12C. In a phase 2 trial, the KRAS inhibitor sotorasib produced a response rate of 37%, a median response duration of 10 months, and a median progression-free survival of 6.8 months in patients with NSCLC.

Data on response duration and progression-free survival are not yet available for adagrasib. However, the duration of response extended past 11 months in four of the six patients who achieved a partial response to adagrasib in the phase 1/1b portion of the KRYSTAL-1 trial.

“What we’ve seen from this data, and data with other agents, is that responses are very heterogeneous,” Dr. Greystoke observed. “A small number of patients do not respond at all. In some patients, responses are short-lived, whilst in other patients, responses are long and still ongoing.”
 

KRYSTAL-1 study design and safety

KRYSTAL-1 is an ongoing phase 1/2 study designed to assess the safety and clinical activity of adagrasib in patients with advanced solid tumors that have a KRAS G12C mutation, including NSCLC.

Dr. Riely reported data on 79 patients with advanced or metastatic NSCLC who had progressed despite being treated with chemotherapy and immunotherapy. Of these, 18 patients had participated in the phase 1/1b dose-escalation and dose-expansion phase of the study, and 61 had participated in the phase 2 portion. Adagrasib was given at a twice-daily dose of 600 mg.

The patients’ median age was 65 years, 85% were White, and 57% were women. Almost all (95%) were current or former smokers, which is unsurprising since the KRAS G12C mutation is rarely seen in never-smokers. Almost all patients had nonsquamous histology (96%) and had received PD-1 or PD-L1 inhibitors (92%).

Treatment-related adverse events of any grade occurred in 85% of patients, and 30% of patients had grade 3-4 events. The most frequent treatment-related grade 3-4 adverse events were fatigue (6%), increased ALT or AST (each 5%), QT prolongation (3%), anemia (2%), nausea (2%), and vomiting (2%).

Two grade 5 adverse events were recorded – a case of pneumonitis in a patient with recurrent pneumonitis and one case of cardiac failure. Adverse events led to discontinuation in 4.5% of patients.
 

Greater effect seen with co-mutation

KRAS is commonly co-mutated, so the investigators performed an exploratory analysis to see if the presence of other mutations – STK11, KEAP1, and TP53 – might affect the results of adagrasib.

A greater objective response rate was seen in patients with the STK11 mutation than in those without it (64% and 33%, respectively). STK11 is associated with poorer responses to immune checkpoint inhibitors.

“We hypothesized that adagrasib treatment recruits T cells into the tumor and that T-cell infiltration may reverse STK11-mediated immune suppression,” Dr. Riely said. This theory seemed to be borne out with further analyses, though Dr. Greystoke raised doubts. There was no sign of STK11 mutations having any effect on response rates with adagrasib in preclinical studies.

Patients with KEAP1 as a co-mutation had a lower response rate than that of those without it (36% and 48%, respectively), which is in keeping with what might be expected. KEAP1 is known to be associated to a poor response to chemotherapy and immunotherapy.

“I think this data is very provocative but needs to be confirmed in larger cohorts,” Dr. Greystoke said. It could mean that adagrasib has the potential to turn a “cold tumor, hot,” enabling the use of immunotherapies.

A new cohort has been included in the KRYSTAL-1 study to further evaluate how having both the KRAS G12C and STK11 mutations may affect treatment with adagrasib.

Data could support drug combination

The adagrasib data lend support to the combination of KRAS G12C inhibitors with other molecularly-targeted treatments for NSCLC, Dr. Greystoke said, such as with tyrosine kinase inhibitors or immunotherapies. He noted that high steady-state levels of adagrasib were detected in the blood, and these levels were well above those needed for potential efficacy.

“This gives us confidence that if we do need to drop the dose below the recommended phase 2 dose to allow potential combinations with a small-molecule inhibitor due to overlapping toxicity or overlapping pharmacokinetics, that it is safe to do and shouldn’t [have an] impact on efficacy,” Dr. Greystoke said. “Overall, all this information will help us drive forward the next round of clinical trials of probably a combination of treatments.”

The KRYSTAL-1 study is supported by Mirati Therapeutics, Inc. Dr. Riely disclosed relationships with Mirati Therapeutics, Merck, Novartis, Pfizer, Takeda, and Roche. Dr. Greystoke was not involved in the study but disclosed relationships with Amgen, AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Merck, Novartis, Pfizer, Lilly, Takeda, and Roche.

The KRAS inhibitor adagrasib produced a high disease control rate in patients with advanced or metastatic non–small cell lung cancer (NSCLC), according to data from the KRYSTAL-1 study.

An objective response rate was seen in 45% of patients, with a further 51% achieving stable disease, for a disease control rate of 96%.

“The vast majority of patients had significant tumor shrinkage,” said study investigator Gregory J. Riely, MD, PhD, when presenting the results at the European Lung Cancer Virtual Congress 2021 (Abstract 990_PR).

Dr. Riely, vice chair of clinical research in the department of medicine at Memorial Sloan Kettering Cancer Center in New York, noted that just 6 of the 70 patients in this phase 1/2 trial showed evidence of measurable tumor growth.

“This new way of targeting an oncogene may very well represent an evolutionary step forward in the management of lung cancer patients, akin to when we first had EGFR inhibitors,” Alastair Greystoke, MBChB, PhD, said in his discussion of the trial.

Dr. Greystoke, a clinical senior lecturer and honorary consultant in medical oncology at Newcastle (England) University, observed that the availability of KRAS-targeting agents could have a large potential impact on clinical practice. They could add another 14% of patients with NSCLC to the list of those who are eligible for molecularly-targeted therapy.

“It may be that soon, almost half our patients with lung adenocarcinoma will have a potential targetable abnormality,” Dr. Greystoke said.
 

Data confirm KRAS as a therapeutic target

Adagrasib is now the second drug to show promise as an inhibitor of KRAS G12C. In a phase 2 trial, the KRAS inhibitor sotorasib produced a response rate of 37%, a median response duration of 10 months, and a median progression-free survival of 6.8 months in patients with NSCLC.

Data on response duration and progression-free survival are not yet available for adagrasib. However, the duration of response extended past 11 months in four of the six patients who achieved a partial response to adagrasib in the phase 1/1b portion of the KRYSTAL-1 trial.

“What we’ve seen from this data, and data with other agents, is that responses are very heterogeneous,” Dr. Greystoke observed. “A small number of patients do not respond at all. In some patients, responses are short-lived, whilst in other patients, responses are long and still ongoing.”
 

KRYSTAL-1 study design and safety

KRYSTAL-1 is an ongoing phase 1/2 study designed to assess the safety and clinical activity of adagrasib in patients with advanced solid tumors that have a KRAS G12C mutation, including NSCLC.

Dr. Riely reported data on 79 patients with advanced or metastatic NSCLC who had progressed despite being treated with chemotherapy and immunotherapy. Of these, 18 patients had participated in the phase 1/1b dose-escalation and dose-expansion phase of the study, and 61 had participated in the phase 2 portion. Adagrasib was given at a twice-daily dose of 600 mg.

The patients’ median age was 65 years, 85% were White, and 57% were women. Almost all (95%) were current or former smokers, which is unsurprising since the KRAS G12C mutation is rarely seen in never-smokers. Almost all patients had nonsquamous histology (96%) and had received PD-1 or PD-L1 inhibitors (92%).

Treatment-related adverse events of any grade occurred in 85% of patients, and 30% of patients had grade 3-4 events. The most frequent treatment-related grade 3-4 adverse events were fatigue (6%), increased ALT or AST (each 5%), QT prolongation (3%), anemia (2%), nausea (2%), and vomiting (2%).

Two grade 5 adverse events were recorded – a case of pneumonitis in a patient with recurrent pneumonitis and one case of cardiac failure. Adverse events led to discontinuation in 4.5% of patients.
 

Greater effect seen with co-mutation

KRAS is commonly co-mutated, so the investigators performed an exploratory analysis to see if the presence of other mutations – STK11, KEAP1, and TP53 – might affect the results of adagrasib.

A greater objective response rate was seen in patients with the STK11 mutation than in those without it (64% and 33%, respectively). STK11 is associated with poorer responses to immune checkpoint inhibitors.

“We hypothesized that adagrasib treatment recruits T cells into the tumor and that T-cell infiltration may reverse STK11-mediated immune suppression,” Dr. Riely said. This theory seemed to be borne out with further analyses, though Dr. Greystoke raised doubts. There was no sign of STK11 mutations having any effect on response rates with adagrasib in preclinical studies.

Patients with KEAP1 as a co-mutation had a lower response rate than that of those without it (36% and 48%, respectively), which is in keeping with what might be expected. KEAP1 is known to be associated to a poor response to chemotherapy and immunotherapy.

“I think this data is very provocative but needs to be confirmed in larger cohorts,” Dr. Greystoke said. It could mean that adagrasib has the potential to turn a “cold tumor, hot,” enabling the use of immunotherapies.

A new cohort has been included in the KRYSTAL-1 study to further evaluate how having both the KRAS G12C and STK11 mutations may affect treatment with adagrasib.

Data could support drug combination

The adagrasib data lend support to the combination of KRAS G12C inhibitors with other molecularly-targeted treatments for NSCLC, Dr. Greystoke said, such as with tyrosine kinase inhibitors or immunotherapies. He noted that high steady-state levels of adagrasib were detected in the blood, and these levels were well above those needed for potential efficacy.

“This gives us confidence that if we do need to drop the dose below the recommended phase 2 dose to allow potential combinations with a small-molecule inhibitor due to overlapping toxicity or overlapping pharmacokinetics, that it is safe to do and shouldn’t [have an] impact on efficacy,” Dr. Greystoke said. “Overall, all this information will help us drive forward the next round of clinical trials of probably a combination of treatments.”

The KRYSTAL-1 study is supported by Mirati Therapeutics, Inc. Dr. Riely disclosed relationships with Mirati Therapeutics, Merck, Novartis, Pfizer, Takeda, and Roche. Dr. Greystoke was not involved in the study but disclosed relationships with Amgen, AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Merck, Novartis, Pfizer, Lilly, Takeda, and Roche.

The KRAS inhibitor adagrasib produced a high disease control rate in patients with advanced or metastatic non–small cell lung cancer (NSCLC), according to data from the KRYSTAL-1 study.

An objective response rate was seen in 45% of patients, with a further 51% achieving stable disease, for a disease control rate of 96%.

“The vast majority of patients had significant tumor shrinkage,” said study investigator Gregory J. Riely, MD, PhD, when presenting the results at the European Lung Cancer Virtual Congress 2021 (Abstract 990_PR).

Dr. Riely, vice chair of clinical research in the department of medicine at Memorial Sloan Kettering Cancer Center in New York, noted that just 6 of the 70 patients in this phase 1/2 trial showed evidence of measurable tumor growth.

“This new way of targeting an oncogene may very well represent an evolutionary step forward in the management of lung cancer patients, akin to when we first had EGFR inhibitors,” Alastair Greystoke, MBChB, PhD, said in his discussion of the trial.

Dr. Greystoke, a clinical senior lecturer and honorary consultant in medical oncology at Newcastle (England) University, observed that the availability of KRAS-targeting agents could have a large potential impact on clinical practice. They could add another 14% of patients with NSCLC to the list of those who are eligible for molecularly-targeted therapy.

“It may be that soon, almost half our patients with lung adenocarcinoma will have a potential targetable abnormality,” Dr. Greystoke said.
 

Data confirm KRAS as a therapeutic target

Adagrasib is now the second drug to show promise as an inhibitor of KRAS G12C. In a phase 2 trial, the KRAS inhibitor sotorasib produced a response rate of 37%, a median response duration of 10 months, and a median progression-free survival of 6.8 months in patients with NSCLC.

Data on response duration and progression-free survival are not yet available for adagrasib. However, the duration of response extended past 11 months in four of the six patients who achieved a partial response to adagrasib in the phase 1/1b portion of the KRYSTAL-1 trial.

“What we’ve seen from this data, and data with other agents, is that responses are very heterogeneous,” Dr. Greystoke observed. “A small number of patients do not respond at all. In some patients, responses are short-lived, whilst in other patients, responses are long and still ongoing.”
 

KRYSTAL-1 study design and safety

KRYSTAL-1 is an ongoing phase 1/2 study designed to assess the safety and clinical activity of adagrasib in patients with advanced solid tumors that have a KRAS G12C mutation, including NSCLC.

Dr. Riely reported data on 79 patients with advanced or metastatic NSCLC who had progressed despite being treated with chemotherapy and immunotherapy. Of these, 18 patients had participated in the phase 1/1b dose-escalation and dose-expansion phase of the study, and 61 had participated in the phase 2 portion. Adagrasib was given at a twice-daily dose of 600 mg.

The patients’ median age was 65 years, 85% were White, and 57% were women. Almost all (95%) were current or former smokers, which is unsurprising since the KRAS G12C mutation is rarely seen in never-smokers. Almost all patients had nonsquamous histology (96%) and had received PD-1 or PD-L1 inhibitors (92%).

Treatment-related adverse events of any grade occurred in 85% of patients, and 30% of patients had grade 3-4 events. The most frequent treatment-related grade 3-4 adverse events were fatigue (6%), increased ALT or AST (each 5%), QT prolongation (3%), anemia (2%), nausea (2%), and vomiting (2%).

Two grade 5 adverse events were recorded – a case of pneumonitis in a patient with recurrent pneumonitis and one case of cardiac failure. Adverse events led to discontinuation in 4.5% of patients.
 

Greater effect seen with co-mutation

KRAS is commonly co-mutated, so the investigators performed an exploratory analysis to see if the presence of other mutations – STK11, KEAP1, and TP53 – might affect the results of adagrasib.

A greater objective response rate was seen in patients with the STK11 mutation than in those without it (64% and 33%, respectively). STK11 is associated with poorer responses to immune checkpoint inhibitors.

“We hypothesized that adagrasib treatment recruits T cells into the tumor and that T-cell infiltration may reverse STK11-mediated immune suppression,” Dr. Riely said. This theory seemed to be borne out with further analyses, though Dr. Greystoke raised doubts. There was no sign of STK11 mutations having any effect on response rates with adagrasib in preclinical studies.

Patients with KEAP1 as a co-mutation had a lower response rate than that of those without it (36% and 48%, respectively), which is in keeping with what might be expected. KEAP1 is known to be associated to a poor response to chemotherapy and immunotherapy.

“I think this data is very provocative but needs to be confirmed in larger cohorts,” Dr. Greystoke said. It could mean that adagrasib has the potential to turn a “cold tumor, hot,” enabling the use of immunotherapies.

A new cohort has been included in the KRYSTAL-1 study to further evaluate how having both the KRAS G12C and STK11 mutations may affect treatment with adagrasib.

Data could support drug combination

The adagrasib data lend support to the combination of KRAS G12C inhibitors with other molecularly-targeted treatments for NSCLC, Dr. Greystoke said, such as with tyrosine kinase inhibitors or immunotherapies. He noted that high steady-state levels of adagrasib were detected in the blood, and these levels were well above those needed for potential efficacy.

“This gives us confidence that if we do need to drop the dose below the recommended phase 2 dose to allow potential combinations with a small-molecule inhibitor due to overlapping toxicity or overlapping pharmacokinetics, that it is safe to do and shouldn’t [have an] impact on efficacy,” Dr. Greystoke said. “Overall, all this information will help us drive forward the next round of clinical trials of probably a combination of treatments.”

The KRYSTAL-1 study is supported by Mirati Therapeutics, Inc. Dr. Riely disclosed relationships with Mirati Therapeutics, Merck, Novartis, Pfizer, Takeda, and Roche. Dr. Greystoke was not involved in the study but disclosed relationships with Amgen, AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Merck, Novartis, Pfizer, Lilly, Takeda, and Roche.