AVAHO

Patients who undergo lung cancer surgery and who receive long-term opioids for pain relief have an elevated risk of all-cause mortality at 2 years, a new study suggests. That risk was 40% higher than among patients who did not receive opioids.

“This is the first study to identify the association of new long-term opioid use with poorer long-term survival outcomes after lung cancer surgery using real-world data based on a national registration database,” said the authors, led by In-Ae Song, MD, Seoul National University Bundang Hospital, Seongnam, South Korea.

“New long-term opioid use may be associated with poor long-term survival outcomes, especially in potent opioid users,” they concluded.

Long-term opioid use might promote protumor activity secondary to immunosuppression along with migration of tumor cells and angiogenesis, the authors suggested.

The study was published online in Regional Anesthesia and Pain.

The finding comes from a study that used the South Korean National Health Insurance database as a nationwide registration data source. “All patients undergoing lung cancer surgery between 2011 and 2018 were included,” the authors noted.

In total, 54,509 patients were included in the final analysis. Six months after undergoing the procedure, 3,325 patients (6.1%) had been prescribed opioids continuously and regularly. These patients constituted the new long-term opioid user group.

This finding fits in with those from past studies that have suggested that new long-term postoperative pain is reported in 4%-12% of patients who undergo lung cancer surgeries, the authors commented.

The new study found that all-cause mortality at 2 years was significantly higher in the new long-term opioid user group than it was in the non–opioid user group (17.3% vs. 9.3%; P < .001).

Moreover, the new long-term opioid user group were at 43% higher risk of 2-year lung cancer mortality and 29% higher risk of 2-year non–lung cancer mortality.

The investigators divided the patients who had received long-term opioids into two subgroups – those who received more potent opioids (1.6%), and those who received less potent opioids (4.5%).

There was a big difference in the results for all-cause mortality.

Compared with nonopioid users, long-term use of less potent opioids was associated with a 2-year mortality risk of only 22% (P < .001), whereas the patients who used potent opioids were at a 92% increased risk of all-cause mortality.

A number of risk factors were associated with an increased rate of new long-term opioid use. These included older age, being male, length of stay in hospital, and comorbidities.

In addition, patients who were more likely to receive long-term opioids included those who had received neoadjuvant and adjuvant chemotherapy and those who had experienced preoperative anxiety disorder or insomnia disorder.

In contrast, patients who underwent video-assisted thoracoscopic surgery were less likely to receive long-term opioids, the authors noted.

The authors disclosed no relevant financial relationships.

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

Patients who undergo lung cancer surgery and who receive long-term opioids for pain relief have an elevated risk of all-cause mortality at 2 years, a new study suggests. That risk was 40% higher than among patients who did not receive opioids.

“This is the first study to identify the association of new long-term opioid use with poorer long-term survival outcomes after lung cancer surgery using real-world data based on a national registration database,” said the authors, led by In-Ae Song, MD, Seoul National University Bundang Hospital, Seongnam, South Korea.

“New long-term opioid use may be associated with poor long-term survival outcomes, especially in potent opioid users,” they concluded.

Long-term opioid use might promote protumor activity secondary to immunosuppression along with migration of tumor cells and angiogenesis, the authors suggested.

The study was published online in Regional Anesthesia and Pain.

The finding comes from a study that used the South Korean National Health Insurance database as a nationwide registration data source. “All patients undergoing lung cancer surgery between 2011 and 2018 were included,” the authors noted.

In total, 54,509 patients were included in the final analysis. Six months after undergoing the procedure, 3,325 patients (6.1%) had been prescribed opioids continuously and regularly. These patients constituted the new long-term opioid user group.

This finding fits in with those from past studies that have suggested that new long-term postoperative pain is reported in 4%-12% of patients who undergo lung cancer surgeries, the authors commented.

The new study found that all-cause mortality at 2 years was significantly higher in the new long-term opioid user group than it was in the non–opioid user group (17.3% vs. 9.3%; P < .001).

Moreover, the new long-term opioid user group were at 43% higher risk of 2-year lung cancer mortality and 29% higher risk of 2-year non–lung cancer mortality.

The investigators divided the patients who had received long-term opioids into two subgroups – those who received more potent opioids (1.6%), and those who received less potent opioids (4.5%).

There was a big difference in the results for all-cause mortality.

Compared with nonopioid users, long-term use of less potent opioids was associated with a 2-year mortality risk of only 22% (P < .001), whereas the patients who used potent opioids were at a 92% increased risk of all-cause mortality.

A number of risk factors were associated with an increased rate of new long-term opioid use. These included older age, being male, length of stay in hospital, and comorbidities.

In addition, patients who were more likely to receive long-term opioids included those who had received neoadjuvant and adjuvant chemotherapy and those who had experienced preoperative anxiety disorder or insomnia disorder.

In contrast, patients who underwent video-assisted thoracoscopic surgery were less likely to receive long-term opioids, the authors noted.

The authors disclosed no relevant financial relationships.

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

Patients who undergo lung cancer surgery and who receive long-term opioids for pain relief have an elevated risk of all-cause mortality at 2 years, a new study suggests. That risk was 40% higher than among patients who did not receive opioids.

“This is the first study to identify the association of new long-term opioid use with poorer long-term survival outcomes after lung cancer surgery using real-world data based on a national registration database,” said the authors, led by In-Ae Song, MD, Seoul National University Bundang Hospital, Seongnam, South Korea.

“New long-term opioid use may be associated with poor long-term survival outcomes, especially in potent opioid users,” they concluded.

Long-term opioid use might promote protumor activity secondary to immunosuppression along with migration of tumor cells and angiogenesis, the authors suggested.

The study was published online in Regional Anesthesia and Pain.

The finding comes from a study that used the South Korean National Health Insurance database as a nationwide registration data source. “All patients undergoing lung cancer surgery between 2011 and 2018 were included,” the authors noted.

In total, 54,509 patients were included in the final analysis. Six months after undergoing the procedure, 3,325 patients (6.1%) had been prescribed opioids continuously and regularly. These patients constituted the new long-term opioid user group.

This finding fits in with those from past studies that have suggested that new long-term postoperative pain is reported in 4%-12% of patients who undergo lung cancer surgeries, the authors commented.

The new study found that all-cause mortality at 2 years was significantly higher in the new long-term opioid user group than it was in the non–opioid user group (17.3% vs. 9.3%; P < .001).

Moreover, the new long-term opioid user group were at 43% higher risk of 2-year lung cancer mortality and 29% higher risk of 2-year non–lung cancer mortality.

The investigators divided the patients who had received long-term opioids into two subgroups – those who received more potent opioids (1.6%), and those who received less potent opioids (4.5%).

There was a big difference in the results for all-cause mortality.

Compared with nonopioid users, long-term use of less potent opioids was associated with a 2-year mortality risk of only 22% (P < .001), whereas the patients who used potent opioids were at a 92% increased risk of all-cause mortality.

A number of risk factors were associated with an increased rate of new long-term opioid use. These included older age, being male, length of stay in hospital, and comorbidities.

In addition, patients who were more likely to receive long-term opioids included those who had received neoadjuvant and adjuvant chemotherapy and those who had experienced preoperative anxiety disorder or insomnia disorder.

In contrast, patients who underwent video-assisted thoracoscopic surgery were less likely to receive long-term opioids, the authors noted.

The authors disclosed no relevant financial relationships.

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

Introduction

Hematologists and oncologists (HO) face mortality daily. “Death Cafe” (DC) is a safe space set aside for open dialogue about death and dying. Despite origins outside the healthcare setting, DC has been used as a framework to help health care students and workers process death and dying. We aim to assess if DC sessions are perceived to have value by HO trainees and faculty.

Methods

HO fellows from Baylor College of Medicine (BCM) and HO Faculty from BCM, mostly those at the Houston Michael E. DeBakey Veterans Affairs Hospital (VA), were offered the opportunity to participate in the DC sessions. Our VA Cancer Center Chaplain was present for all sessions and helped facilitate the conversation. HO fellows who were invited to a DC and attended were emailed a survey questionnaire after the activity via survey monkey. The sessions and the surveys were not compulsory. Their participation in the session and completion of surveys implied informed consent. After IRB approval, we reviewed responses for the study groups. Sessions were held in person pre-pandemic in 2019 and virtually during the COVID-19 pandemic in 2022.

Results

Five fellows responded to our survey in 2019 and 7 in 2022 for a total of 12 respondents. 100% of respondents had been emotionally affected by a patient’s death. 82% had been emotionally affected by a patient’s death during the preceding 3 months. 90% had previously discussed their emotions relating to patient death with others. 83% would participate in DC again and 92% would recommend DC to a colleague. One 2019 participant commented that they thought attendings needed the session more than fellows, 2 2022 participants commented that they believe the meeting would be better in person. One 2022 participant commented they thought DC “is a good platform to vent emotions, identify self-destructive thoughts and better coping mechanisms.”

Conclusions 

DC provides a framework for HC to share personal and professional experience with mortality from a human perspective and support each other. This approach may be useful for HO departments or fellowships to offer as an opportunity to process end-of-life matters experienced as providers and finite humans.

Introduction

Hematologists and oncologists (HO) face mortality daily. “Death Cafe” (DC) is a safe space set aside for open dialogue about death and dying. Despite origins outside the healthcare setting, DC has been used as a framework to help health care students and workers process death and dying. We aim to assess if DC sessions are perceived to have value by HO trainees and faculty.

Methods

HO fellows from Baylor College of Medicine (BCM) and HO Faculty from BCM, mostly those at the Houston Michael E. DeBakey Veterans Affairs Hospital (VA), were offered the opportunity to participate in the DC sessions. Our VA Cancer Center Chaplain was present for all sessions and helped facilitate the conversation. HO fellows who were invited to a DC and attended were emailed a survey questionnaire after the activity via survey monkey. The sessions and the surveys were not compulsory. Their participation in the session and completion of surveys implied informed consent. After IRB approval, we reviewed responses for the study groups. Sessions were held in person pre-pandemic in 2019 and virtually during the COVID-19 pandemic in 2022.

Results

Five fellows responded to our survey in 2019 and 7 in 2022 for a total of 12 respondents. 100% of respondents had been emotionally affected by a patient’s death. 82% had been emotionally affected by a patient’s death during the preceding 3 months. 90% had previously discussed their emotions relating to patient death with others. 83% would participate in DC again and 92% would recommend DC to a colleague. One 2019 participant commented that they thought attendings needed the session more than fellows, 2 2022 participants commented that they believe the meeting would be better in person. One 2022 participant commented they thought DC “is a good platform to vent emotions, identify self-destructive thoughts and better coping mechanisms.”

Conclusions 

DC provides a framework for HC to share personal and professional experience with mortality from a human perspective and support each other. This approach may be useful for HO departments or fellowships to offer as an opportunity to process end-of-life matters experienced as providers and finite humans.

Introduction

Hematologists and oncologists (HO) face mortality daily. “Death Cafe” (DC) is a safe space set aside for open dialogue about death and dying. Despite origins outside the healthcare setting, DC has been used as a framework to help health care students and workers process death and dying. We aim to assess if DC sessions are perceived to have value by HO trainees and faculty.

Methods

HO fellows from Baylor College of Medicine (BCM) and HO Faculty from BCM, mostly those at the Houston Michael E. DeBakey Veterans Affairs Hospital (VA), were offered the opportunity to participate in the DC sessions. Our VA Cancer Center Chaplain was present for all sessions and helped facilitate the conversation. HO fellows who were invited to a DC and attended were emailed a survey questionnaire after the activity via survey monkey. The sessions and the surveys were not compulsory. Their participation in the session and completion of surveys implied informed consent. After IRB approval, we reviewed responses for the study groups. Sessions were held in person pre-pandemic in 2019 and virtually during the COVID-19 pandemic in 2022.

Results

Five fellows responded to our survey in 2019 and 7 in 2022 for a total of 12 respondents. 100% of respondents had been emotionally affected by a patient’s death. 82% had been emotionally affected by a patient’s death during the preceding 3 months. 90% had previously discussed their emotions relating to patient death with others. 83% would participate in DC again and 92% would recommend DC to a colleague. One 2019 participant commented that they thought attendings needed the session more than fellows, 2 2022 participants commented that they believe the meeting would be better in person. One 2022 participant commented they thought DC “is a good platform to vent emotions, identify self-destructive thoughts and better coping mechanisms.”

Conclusions 

DC provides a framework for HC to share personal and professional experience with mortality from a human perspective and support each other. This approach may be useful for HO departments or fellowships to offer as an opportunity to process end-of-life matters experienced as providers and finite humans.

PARIS – Adding pembrolizumab (Keytruda) to chemoradiotherapy did not significantly improve event-free survival, compared with CRT plus placebo as first-line therapy for patients with locally advanced head and neck squamous cell cancers (HNSCC), reported investigators of the KEYNOTE-412 trial.

Among 804 patients with newly diagnosed, pathologically proven, unresected locally advanced head and neck squamous cell carcinomas who were followed for a median of 47.7 months, the event-free survival (EFS) rate with the pembrolizumab/CRT combination followed by maintenance pembrolizumab was 63.2%, compared with 56.2% for CRT plus placebo. This translated into a nonsignificant hazard ratio of 0.83, said Jean-Pascal Machiels, MD, PhD, at the annual meeting of the European Society for Medical Oncology.

Despite the trial failing to meet its primary endpoint, Dr. Machiels expressed optimism about the results.

“Pembrolizumab with chemoradiation was associated with a favorable trend toward improved event-free survival versus placebo plus chemoradiation in patients with locally advanced head and neck cancer,” he said.

He noted that the 2-year EFS rate was 63% with pembrolizumab, compared with 56% with placebo.

The data also support the hypothesis that programmed death–ligand 1 (PD-L1) expression as measured by a combined positive score (CPS) could be a predictive biomarker for identifying those patients most likely to respond to the immune checkpoint inhibitor, he added.

KEYNOTE-412 details

The rationale for combining the checkpoint inhibitors pembrolizumab with chemoradiotherapy comes from the KEYNOTE-048 trial results of which showed a survival improvement for the use of pembrolizumab plus a platinum-containing regimen as a first-line therapy for recurrent or metastatic HNSCC, as well as pembrolizumab monotherapy for patients with PD-L1 CPS of 1 or greater.

In the current study, Dr. Machiels and colleagues studied whether adding pembrolizumab to CRT could benefit patients with treatment-naive unresected, locally advanced HNSCC.

Eligible patients included those with stage T3 or T4, N0-N3 or any N2a-3 (T1-T4) cancers of the larynx, hypopharynx, or oral cavity, and either p16-negative oropharynx cancers or T4 or N3 p16-positive oropharynx cancer. Patients were required to be eligible for high-dose cisplatin-based CRT.

A total of 804 patients were randomized, 402 in each arm, to receive either pembrolizumab 200 mg intravenously every 3 weeks for 3 cycles plus CRT followed by maintenance pembrolizumab for 14 cycles, or to placebo plus CRT followed by placebo maintenance.

As noted before, there was no significant difference between the study arms for the primary endpoint of EFS. The 24-month EFS rate was 63.2% for the pembrolizumab group, compared with 56.2% for controls. The respective 6-month EFS rates were 57.4% versus 52.1%.­

In a post hoc analysis, both EFS and overall survival were numerically with pembrolizumab among patients with PD-L1 CPS of 20 or greater. The respective 2- and 3-year EFS rates were 71.2% versus 62.6%, and 66.7% versus 57.2%.

The 24-months overall survival rates were 83.3% with pembrolizumab and 79.9% with placebo, and 36-month rates were 79.1% and 73%, respectively.

Neither EFS rates nor OS rates among patients in this subgroup differed significantly; however, there were no new safety signals with the combination, Dr. Machiels said. The incidence of grade 3 or greater adverse events was 92.2% in the pembrolizumab arm versus 88.4% in the placebo arm. Four patients in the pembrolizumab arm and six in the control arm died from treatment-related causes.
 

Benefit still to be proven

In a media briefing held prior to his presentation, Dr. Machiels was asked how he could justify his conclusions about a benefit for adding pembrolizumab given that there was no difference between the treatment groups for the primary endpoint.

He said that when the investigators designed the trial 7 years ago, the CPS score for PD-L1 expression had not yet been developed, and that if it had been they might have designed the trial to explore the effect of the pembrolizumab chemoradiation combination according to CPS subgroups.

He also pointed to the numerically superior 2-year EFS and overall rates.

In the presidential symposium, James Larkin, MD, PhD, an invited discussant from the Royal Marsden Hospital, London, said that chemotherapy and anti–PD-1 therapies are known to offer benefit in advanced cancers despite the trial’s failure.

“There is a signal, particularly as we’ve seen in the high PD-L1 group,” he said, noting that the signal was consistent with that seen in the JAVELIN 100 study, which was also a negative trial. He cautioned against relying too heavily on the comparison, however, as JAVELIN 100 was conducted with avelumab, a PD-L1 inhibitor, whereas pembrolizumab is a PD-1 inhibitor.

“Could there be an issue here with treatment schedule? An example and a comparison might be the PACIFIC study in non–small cell lung cancer, which is a positive trial, where actually the checkpoint inhibit with durvalumab was given immediately after the chemoradiotherapy, leading to benefit, rather than being concurrent,” he said.

Dr. Larkin also questioned whether, as codiscussant Sherene Loi, MD, PhD, from the Peter MacCallum Cancer Center, Melbourne, suggested radiotherapy to lymph nodes might alter the immune response to checkpoint inhibitors.

“Clearly radiotherapy is the central component of treatment in this setting, so it would be quite difficult to scale too much on that, but the question is: ‘Could it be modified?’ For example, just to irradiate the primary tumor and involved lymph nodes and potentially spare noninvolved lymph nodes,” he said.

The KEYNOTE-412 study was funded by Merck Sharp & Dohme. Dr. Machiels reported uncompensated consulting to the company. Dr. Larkin reported consulting for and receiving honoraria from Merck and others. Dr. Loi reported uncompensated advisory board activity for Merck and others.

PARIS – Adding pembrolizumab (Keytruda) to chemoradiotherapy did not significantly improve event-free survival, compared with CRT plus placebo as first-line therapy for patients with locally advanced head and neck squamous cell cancers (HNSCC), reported investigators of the KEYNOTE-412 trial.

Among 804 patients with newly diagnosed, pathologically proven, unresected locally advanced head and neck squamous cell carcinomas who were followed for a median of 47.7 months, the event-free survival (EFS) rate with the pembrolizumab/CRT combination followed by maintenance pembrolizumab was 63.2%, compared with 56.2% for CRT plus placebo. This translated into a nonsignificant hazard ratio of 0.83, said Jean-Pascal Machiels, MD, PhD, at the annual meeting of the European Society for Medical Oncology.

Despite the trial failing to meet its primary endpoint, Dr. Machiels expressed optimism about the results.

“Pembrolizumab with chemoradiation was associated with a favorable trend toward improved event-free survival versus placebo plus chemoradiation in patients with locally advanced head and neck cancer,” he said.

He noted that the 2-year EFS rate was 63% with pembrolizumab, compared with 56% with placebo.

The data also support the hypothesis that programmed death–ligand 1 (PD-L1) expression as measured by a combined positive score (CPS) could be a predictive biomarker for identifying those patients most likely to respond to the immune checkpoint inhibitor, he added.

KEYNOTE-412 details

The rationale for combining the checkpoint inhibitors pembrolizumab with chemoradiotherapy comes from the KEYNOTE-048 trial results of which showed a survival improvement for the use of pembrolizumab plus a platinum-containing regimen as a first-line therapy for recurrent or metastatic HNSCC, as well as pembrolizumab monotherapy for patients with PD-L1 CPS of 1 or greater.

In the current study, Dr. Machiels and colleagues studied whether adding pembrolizumab to CRT could benefit patients with treatment-naive unresected, locally advanced HNSCC.

Eligible patients included those with stage T3 or T4, N0-N3 or any N2a-3 (T1-T4) cancers of the larynx, hypopharynx, or oral cavity, and either p16-negative oropharynx cancers or T4 or N3 p16-positive oropharynx cancer. Patients were required to be eligible for high-dose cisplatin-based CRT.

A total of 804 patients were randomized, 402 in each arm, to receive either pembrolizumab 200 mg intravenously every 3 weeks for 3 cycles plus CRT followed by maintenance pembrolizumab for 14 cycles, or to placebo plus CRT followed by placebo maintenance.

As noted before, there was no significant difference between the study arms for the primary endpoint of EFS. The 24-month EFS rate was 63.2% for the pembrolizumab group, compared with 56.2% for controls. The respective 6-month EFS rates were 57.4% versus 52.1%.­

In a post hoc analysis, both EFS and overall survival were numerically with pembrolizumab among patients with PD-L1 CPS of 20 or greater. The respective 2- and 3-year EFS rates were 71.2% versus 62.6%, and 66.7% versus 57.2%.

The 24-months overall survival rates were 83.3% with pembrolizumab and 79.9% with placebo, and 36-month rates were 79.1% and 73%, respectively.

Neither EFS rates nor OS rates among patients in this subgroup differed significantly; however, there were no new safety signals with the combination, Dr. Machiels said. The incidence of grade 3 or greater adverse events was 92.2% in the pembrolizumab arm versus 88.4% in the placebo arm. Four patients in the pembrolizumab arm and six in the control arm died from treatment-related causes.
 

Benefit still to be proven

In a media briefing held prior to his presentation, Dr. Machiels was asked how he could justify his conclusions about a benefit for adding pembrolizumab given that there was no difference between the treatment groups for the primary endpoint.

He said that when the investigators designed the trial 7 years ago, the CPS score for PD-L1 expression had not yet been developed, and that if it had been they might have designed the trial to explore the effect of the pembrolizumab chemoradiation combination according to CPS subgroups.

He also pointed to the numerically superior 2-year EFS and overall rates.

In the presidential symposium, James Larkin, MD, PhD, an invited discussant from the Royal Marsden Hospital, London, said that chemotherapy and anti–PD-1 therapies are known to offer benefit in advanced cancers despite the trial’s failure.

“There is a signal, particularly as we’ve seen in the high PD-L1 group,” he said, noting that the signal was consistent with that seen in the JAVELIN 100 study, which was also a negative trial. He cautioned against relying too heavily on the comparison, however, as JAVELIN 100 was conducted with avelumab, a PD-L1 inhibitor, whereas pembrolizumab is a PD-1 inhibitor.

“Could there be an issue here with treatment schedule? An example and a comparison might be the PACIFIC study in non–small cell lung cancer, which is a positive trial, where actually the checkpoint inhibit with durvalumab was given immediately after the chemoradiotherapy, leading to benefit, rather than being concurrent,” he said.

Dr. Larkin also questioned whether, as codiscussant Sherene Loi, MD, PhD, from the Peter MacCallum Cancer Center, Melbourne, suggested radiotherapy to lymph nodes might alter the immune response to checkpoint inhibitors.

“Clearly radiotherapy is the central component of treatment in this setting, so it would be quite difficult to scale too much on that, but the question is: ‘Could it be modified?’ For example, just to irradiate the primary tumor and involved lymph nodes and potentially spare noninvolved lymph nodes,” he said.

The KEYNOTE-412 study was funded by Merck Sharp & Dohme. Dr. Machiels reported uncompensated consulting to the company. Dr. Larkin reported consulting for and receiving honoraria from Merck and others. Dr. Loi reported uncompensated advisory board activity for Merck and others.

PARIS – Adding pembrolizumab (Keytruda) to chemoradiotherapy did not significantly improve event-free survival, compared with CRT plus placebo as first-line therapy for patients with locally advanced head and neck squamous cell cancers (HNSCC), reported investigators of the KEYNOTE-412 trial.

Among 804 patients with newly diagnosed, pathologically proven, unresected locally advanced head and neck squamous cell carcinomas who were followed for a median of 47.7 months, the event-free survival (EFS) rate with the pembrolizumab/CRT combination followed by maintenance pembrolizumab was 63.2%, compared with 56.2% for CRT plus placebo. This translated into a nonsignificant hazard ratio of 0.83, said Jean-Pascal Machiels, MD, PhD, at the annual meeting of the European Society for Medical Oncology.

Despite the trial failing to meet its primary endpoint, Dr. Machiels expressed optimism about the results.

“Pembrolizumab with chemoradiation was associated with a favorable trend toward improved event-free survival versus placebo plus chemoradiation in patients with locally advanced head and neck cancer,” he said.

He noted that the 2-year EFS rate was 63% with pembrolizumab, compared with 56% with placebo.

The data also support the hypothesis that programmed death–ligand 1 (PD-L1) expression as measured by a combined positive score (CPS) could be a predictive biomarker for identifying those patients most likely to respond to the immune checkpoint inhibitor, he added.

KEYNOTE-412 details

The rationale for combining the checkpoint inhibitors pembrolizumab with chemoradiotherapy comes from the KEYNOTE-048 trial results of which showed a survival improvement for the use of pembrolizumab plus a platinum-containing regimen as a first-line therapy for recurrent or metastatic HNSCC, as well as pembrolizumab monotherapy for patients with PD-L1 CPS of 1 or greater.

In the current study, Dr. Machiels and colleagues studied whether adding pembrolizumab to CRT could benefit patients with treatment-naive unresected, locally advanced HNSCC.

Eligible patients included those with stage T3 or T4, N0-N3 or any N2a-3 (T1-T4) cancers of the larynx, hypopharynx, or oral cavity, and either p16-negative oropharynx cancers or T4 or N3 p16-positive oropharynx cancer. Patients were required to be eligible for high-dose cisplatin-based CRT.

A total of 804 patients were randomized, 402 in each arm, to receive either pembrolizumab 200 mg intravenously every 3 weeks for 3 cycles plus CRT followed by maintenance pembrolizumab for 14 cycles, or to placebo plus CRT followed by placebo maintenance.

As noted before, there was no significant difference between the study arms for the primary endpoint of EFS. The 24-month EFS rate was 63.2% for the pembrolizumab group, compared with 56.2% for controls. The respective 6-month EFS rates were 57.4% versus 52.1%.­

In a post hoc analysis, both EFS and overall survival were numerically with pembrolizumab among patients with PD-L1 CPS of 20 or greater. The respective 2- and 3-year EFS rates were 71.2% versus 62.6%, and 66.7% versus 57.2%.

The 24-months overall survival rates were 83.3% with pembrolizumab and 79.9% with placebo, and 36-month rates were 79.1% and 73%, respectively.

Neither EFS rates nor OS rates among patients in this subgroup differed significantly; however, there were no new safety signals with the combination, Dr. Machiels said. The incidence of grade 3 or greater adverse events was 92.2% in the pembrolizumab arm versus 88.4% in the placebo arm. Four patients in the pembrolizumab arm and six in the control arm died from treatment-related causes.
 

Benefit still to be proven

In a media briefing held prior to his presentation, Dr. Machiels was asked how he could justify his conclusions about a benefit for adding pembrolizumab given that there was no difference between the treatment groups for the primary endpoint.

He said that when the investigators designed the trial 7 years ago, the CPS score for PD-L1 expression had not yet been developed, and that if it had been they might have designed the trial to explore the effect of the pembrolizumab chemoradiation combination according to CPS subgroups.

He also pointed to the numerically superior 2-year EFS and overall rates.

In the presidential symposium, James Larkin, MD, PhD, an invited discussant from the Royal Marsden Hospital, London, said that chemotherapy and anti–PD-1 therapies are known to offer benefit in advanced cancers despite the trial’s failure.

“There is a signal, particularly as we’ve seen in the high PD-L1 group,” he said, noting that the signal was consistent with that seen in the JAVELIN 100 study, which was also a negative trial. He cautioned against relying too heavily on the comparison, however, as JAVELIN 100 was conducted with avelumab, a PD-L1 inhibitor, whereas pembrolizumab is a PD-1 inhibitor.

“Could there be an issue here with treatment schedule? An example and a comparison might be the PACIFIC study in non–small cell lung cancer, which is a positive trial, where actually the checkpoint inhibit with durvalumab was given immediately after the chemoradiotherapy, leading to benefit, rather than being concurrent,” he said.

Dr. Larkin also questioned whether, as codiscussant Sherene Loi, MD, PhD, from the Peter MacCallum Cancer Center, Melbourne, suggested radiotherapy to lymph nodes might alter the immune response to checkpoint inhibitors.

“Clearly radiotherapy is the central component of treatment in this setting, so it would be quite difficult to scale too much on that, but the question is: ‘Could it be modified?’ For example, just to irradiate the primary tumor and involved lymph nodes and potentially spare noninvolved lymph nodes,” he said.

The KEYNOTE-412 study was funded by Merck Sharp & Dohme. Dr. Machiels reported uncompensated consulting to the company. Dr. Larkin reported consulting for and receiving honoraria from Merck and others. Dr. Loi reported uncompensated advisory board activity for Merck and others.

In non–small cell lung cancer (NSCLC), mutations to the epidermal growth factor receptor (EGFR) gene are generally associated with a poor response to immune checkpoint inhibitor (ICI) therapies. However, there is a range of different EGFR mutations, and different mutation combinations can lead to different tumor characteristics that might in turn affect response to therapy.

A new real-world analysis of 159 NSCLC patients found that a combination of a mutation of the TP53 tumor suppressor gene and the EGFR Ex20 mutation is associated with worse disease outcomes, compared to patients with the EGFR Ex20 mutation alone. But the news wasn’t all bad. The same group of patients also responded better to ICB (immune checkpoint blockade) therapy than did the broader population of EGFR Ex20 patients.

The EGFR Ex20 mutation occurs in about 4% of NSCLC cases, while TP53 is quite common: The new study found a frequency of 43.9%. “We first have to mention that the findings regarding TP53 do not reach statistical significance; however, the trend is very strong, and results might be hampered due to small sample sizes. We think it is [appropriate] to exhaust more treatment options for these patients, especially targeted approaches with newer drugs that specifically target exon 20 insertions, as these drugs were not applied in our cohort,” Anna Kron, Dr. rer. medic., said in an email exchange. Dr. Kron presented the results at a poster session in Paris at the ESMO Congress. She is a researcher at University Hospital of Cologne, Germany.

The ImmunoTarget study, published in 2019, examined over 500 NSCLC patients with a range of driver mutations including EGFR and found that they responded poorly to ICIs in comparison to KRAS mutations.

But Dr. Kron’s group was not convinced. “Ex20 mutations differ clinically from other tyrosine kinase mutations in EGFR. We set out this study to rechallenge the paradigm of impaired benefit from ICI in EGFR-mutated patients, as we consider these mutations not interchangeable with other EGFR mutations,” Dr. Kron said.

“We would postulate that in EGFR Exon 20 mutations, ICI and specific inhibitors should be part of the therapeutic course. In patients with co-occurring TP53 mutations, treatment escalation could be considered,” Dr. Kron said.

The study included 159 patients with advanced NSCLC with the EGFR exon 20 insertion, who were treated between 2014 and 2020 at German hospitals. Among the patients, 37.7% were female; mean age at diagnosis was 65.87 years; 50.3% had a smoking history and 38.4% did not (data were unavailable for the rest); and 9.4% of tumors were stage I, 4.4% stage II, 8.2% stage IIIA, 3.8% stage IIIB, and 74.2% stage IV.

Over a follow-up of 4.1 years, there was a trend toward longer survival among patients with TP53 wild type (OS, 20 versus 12 months; P = .092). Sixty-six patients who received ICI therapy had better OS compared with those who did not (22 versus 10 months; P = .018). Among patients with co-occurring TP53 mutations, receipt of ICI therapy was associated with longer OS (16 versus 8 months; P = .048). There was a trend toward patients with TP53 wild type treated with ICI faring better than those who didn’t receive ICI (27.0 months versus 11.0 months; P = .109).

The researchers are continuing to study patients with EGFR Ex20 to better understand the role of TP53 and ICI therapy in these patients.

The study received no funding. Dr. Kron has no relevant financial disclosures.

In non–small cell lung cancer (NSCLC), mutations to the epidermal growth factor receptor (EGFR) gene are generally associated with a poor response to immune checkpoint inhibitor (ICI) therapies. However, there is a range of different EGFR mutations, and different mutation combinations can lead to different tumor characteristics that might in turn affect response to therapy.

A new real-world analysis of 159 NSCLC patients found that a combination of a mutation of the TP53 tumor suppressor gene and the EGFR Ex20 mutation is associated with worse disease outcomes, compared to patients with the EGFR Ex20 mutation alone. But the news wasn’t all bad. The same group of patients also responded better to ICB (immune checkpoint blockade) therapy than did the broader population of EGFR Ex20 patients.

The EGFR Ex20 mutation occurs in about 4% of NSCLC cases, while TP53 is quite common: The new study found a frequency of 43.9%. “We first have to mention that the findings regarding TP53 do not reach statistical significance; however, the trend is very strong, and results might be hampered due to small sample sizes. We think it is [appropriate] to exhaust more treatment options for these patients, especially targeted approaches with newer drugs that specifically target exon 20 insertions, as these drugs were not applied in our cohort,” Anna Kron, Dr. rer. medic., said in an email exchange. Dr. Kron presented the results at a poster session in Paris at the ESMO Congress. She is a researcher at University Hospital of Cologne, Germany.

The ImmunoTarget study, published in 2019, examined over 500 NSCLC patients with a range of driver mutations including EGFR and found that they responded poorly to ICIs in comparison to KRAS mutations.

But Dr. Kron’s group was not convinced. “Ex20 mutations differ clinically from other tyrosine kinase mutations in EGFR. We set out this study to rechallenge the paradigm of impaired benefit from ICI in EGFR-mutated patients, as we consider these mutations not interchangeable with other EGFR mutations,” Dr. Kron said.

“We would postulate that in EGFR Exon 20 mutations, ICI and specific inhibitors should be part of the therapeutic course. In patients with co-occurring TP53 mutations, treatment escalation could be considered,” Dr. Kron said.

The study included 159 patients with advanced NSCLC with the EGFR exon 20 insertion, who were treated between 2014 and 2020 at German hospitals. Among the patients, 37.7% were female; mean age at diagnosis was 65.87 years; 50.3% had a smoking history and 38.4% did not (data were unavailable for the rest); and 9.4% of tumors were stage I, 4.4% stage II, 8.2% stage IIIA, 3.8% stage IIIB, and 74.2% stage IV.

Over a follow-up of 4.1 years, there was a trend toward longer survival among patients with TP53 wild type (OS, 20 versus 12 months; P = .092). Sixty-six patients who received ICI therapy had better OS compared with those who did not (22 versus 10 months; P = .018). Among patients with co-occurring TP53 mutations, receipt of ICI therapy was associated with longer OS (16 versus 8 months; P = .048). There was a trend toward patients with TP53 wild type treated with ICI faring better than those who didn’t receive ICI (27.0 months versus 11.0 months; P = .109).

The researchers are continuing to study patients with EGFR Ex20 to better understand the role of TP53 and ICI therapy in these patients.

The study received no funding. Dr. Kron has no relevant financial disclosures.

In non–small cell lung cancer (NSCLC), mutations to the epidermal growth factor receptor (EGFR) gene are generally associated with a poor response to immune checkpoint inhibitor (ICI) therapies. However, there is a range of different EGFR mutations, and different mutation combinations can lead to different tumor characteristics that might in turn affect response to therapy.

A new real-world analysis of 159 NSCLC patients found that a combination of a mutation of the TP53 tumor suppressor gene and the EGFR Ex20 mutation is associated with worse disease outcomes, compared to patients with the EGFR Ex20 mutation alone. But the news wasn’t all bad. The same group of patients also responded better to ICB (immune checkpoint blockade) therapy than did the broader population of EGFR Ex20 patients.

The EGFR Ex20 mutation occurs in about 4% of NSCLC cases, while TP53 is quite common: The new study found a frequency of 43.9%. “We first have to mention that the findings regarding TP53 do not reach statistical significance; however, the trend is very strong, and results might be hampered due to small sample sizes. We think it is [appropriate] to exhaust more treatment options for these patients, especially targeted approaches with newer drugs that specifically target exon 20 insertions, as these drugs were not applied in our cohort,” Anna Kron, Dr. rer. medic., said in an email exchange. Dr. Kron presented the results at a poster session in Paris at the ESMO Congress. She is a researcher at University Hospital of Cologne, Germany.

The ImmunoTarget study, published in 2019, examined over 500 NSCLC patients with a range of driver mutations including EGFR and found that they responded poorly to ICIs in comparison to KRAS mutations.

But Dr. Kron’s group was not convinced. “Ex20 mutations differ clinically from other tyrosine kinase mutations in EGFR. We set out this study to rechallenge the paradigm of impaired benefit from ICI in EGFR-mutated patients, as we consider these mutations not interchangeable with other EGFR mutations,” Dr. Kron said.

“We would postulate that in EGFR Exon 20 mutations, ICI and specific inhibitors should be part of the therapeutic course. In patients with co-occurring TP53 mutations, treatment escalation could be considered,” Dr. Kron said.

The study included 159 patients with advanced NSCLC with the EGFR exon 20 insertion, who were treated between 2014 and 2020 at German hospitals. Among the patients, 37.7% were female; mean age at diagnosis was 65.87 years; 50.3% had a smoking history and 38.4% did not (data were unavailable for the rest); and 9.4% of tumors were stage I, 4.4% stage II, 8.2% stage IIIA, 3.8% stage IIIB, and 74.2% stage IV.

Over a follow-up of 4.1 years, there was a trend toward longer survival among patients with TP53 wild type (OS, 20 versus 12 months; P = .092). Sixty-six patients who received ICI therapy had better OS compared with those who did not (22 versus 10 months; P = .018). Among patients with co-occurring TP53 mutations, receipt of ICI therapy was associated with longer OS (16 versus 8 months; P = .048). There was a trend toward patients with TP53 wild type treated with ICI faring better than those who didn’t receive ICI (27.0 months versus 11.0 months; P = .109).

The researchers are continuing to study patients with EGFR Ex20 to better understand the role of TP53 and ICI therapy in these patients.

The study received no funding. Dr. Kron has no relevant financial disclosures.

Cardiometabolic and respiratory comorbidities are associated with worse survival in patients with non–small cell lung cancer (NSCLC), and new research suggests a potential mechanism.

Prior studies had shown mixed results when it came to these comorbidities and survival, according to study coauthor author Geoffrey Liu, MD, who is an epidemiology researcher at the University of Toronto Princess Margaret Cancer Centre. The new work represents data from multiple continents, from various ethnicities and cultures.

“We found that comorbidities had much greater impact on earlier than later stages of lung cancer, consistent with this previous study,” said Dr. Liu in an email. The study was presented by Miguel Garcia-Pardo, who is a researcher at University of Toronto Princess Margaret Cancer Centre, during a poster session at the annual meeting of the European Society for Medical Oncology.

“Deaths from [cardiometabolic] comorbidities were mainly from non–lung cancer competing causes, whereas the deaths from respiratory comorbidities were primarily driven by lung cancer specific survival, i.e., deaths from lung cancer itself. We conclude that it is critical to understand how these patients with different comorbidities died, as it would impact decisions on treatment planning and mitigation strategies,” Dr. Liu said.

Dr. Liu noted that controlling cardiometabolic risk factors like diabetes and hypertension is typically de-emphasized after diagnosis with early-stage lung cancer. The rationale is often that the lung cancer is a more acute concern than longer-term cardiometabolic risks. “The data from our analyses suggest a rethinking of this strategy. We need to pay more attention to controlling cardiovascular risk factors in early-stage lung cancer,” Dr. Liu said.

The findings also suggest that respiratory comorbidities should be managed more aggressively. That would allow more patients to undergo treatments like surgery and stereotactic radiation.

The Clinical Outcome Studies of the International Lung Cancer Consortium drew from two dozen studies conducted across five continents. It examined clinical, epidemiologic, genetic, and genomic factors and their potential influence on NSCLC outcomes. Cardiometabolic comorbidities included coronary artery disease, diabetes, vascular related diseases, and other heart diseases. Respiratory comorbidities included chronic obstructive pulmonary disease and asthma.

The analysis included 16,354 patients. Among patients with stage I NSCLC, there was an association between reduced overall survival (OS) and cardiometabolic comorbidity (adjusted hazard ratio, 1.17; P = .01) and respiratory comorbidity (aHR, 1.36; P < .001). For stage II/III patients, there was no significant association between OS and cardiometabolic comorbidities, but respiratory comorbidity was associated with worse OS (aHR, 1.15; P < .001). In stage 4, worse OS was associated with both cardiometabolic health comorbidity (aHR, 1.11; P = .03), but not respiratory comorbidity.

Among patients with stage IV NSCLC, there were no associations between overall survival or lung cancer–specific survival (LCSS) and respiratory or cardiometabolic risk factors. However, an examination of cause of death found a different pattern in patients with stage IB-IIIA disease: LCSS was worse among patients with respiratory comorbidities (aHR, 1.21; 95% CI, 1.09-1.34). Among those with cardiovascular comorbidities, the risk of non-NSCLC mortality was higher (aHR, 1.36; 95% CI, 1.15-1.63). The presence of respiratory comorbidity was associated with a reduced probability of undergoing surgical resection for both stage I (adjusted odds ratio, 0.45; 95% CI, 0.35-0.59) and stage II/III patients (aOR, 0.66; 95% CI, 0.53-0.80).

There was an association between non-NSCLC mortality and cardiometabolic comorbidities in stage IA (aHR, 1.37; 95% CI, 1.06-1.77) and in stages IB-IIIA (aHR, 1.32; 95% CI, 1.03-1.71) NSCLC. There were also associations between NSCLC mortality and respiratory comorbidity among stage IA (aHR, 1.51; 95% CI, 1.17-1.95) and stages IB-IIIA (aHR, 1.20; 95% CI, 1.06-1.36) NSCLC. There were no associations between respiratory comorbidity and non-NSCLC mortality.

Respiratory comorbidity was associated with a lower chance of undergoing surgical resection in stage IA (aHR, 0.54; 95% CI, 0.35-0.83) and stage IB-IIIA (aHR, 0.57; 95% CI, 0.46-0.70) cancers. Cardiometabolic comorbidity was associated with a lower rate of surgical resection only in stage 1B-3A patients (aHR, 0.73; 95% CI, 0.56-0.96). Among those who underwent resection, stage IA patients were less likely to die of lung cancer (aHR, 0.38; 95% CI, 0.28-0.52) but more likely to die of other causes (aHR, 1.73; 95% CI, 1.07-1.78). Stage IB-IIIA patients who underwent resection were less likely to die of lung cancer (aHR, 0.37; 95%, 0.32-0.42), but there was no significant association with non–lung cancer mortality.

The study was funded by the Lusi Wong Family Fund and the Alan Brown Chair. Dr. Liu has no relevant financial disclosures.

Cardiometabolic and respiratory comorbidities are associated with worse survival in patients with non–small cell lung cancer (NSCLC), and new research suggests a potential mechanism.

Prior studies had shown mixed results when it came to these comorbidities and survival, according to study coauthor author Geoffrey Liu, MD, who is an epidemiology researcher at the University of Toronto Princess Margaret Cancer Centre. The new work represents data from multiple continents, from various ethnicities and cultures.

“We found that comorbidities had much greater impact on earlier than later stages of lung cancer, consistent with this previous study,” said Dr. Liu in an email. The study was presented by Miguel Garcia-Pardo, who is a researcher at University of Toronto Princess Margaret Cancer Centre, during a poster session at the annual meeting of the European Society for Medical Oncology.

“Deaths from [cardiometabolic] comorbidities were mainly from non–lung cancer competing causes, whereas the deaths from respiratory comorbidities were primarily driven by lung cancer specific survival, i.e., deaths from lung cancer itself. We conclude that it is critical to understand how these patients with different comorbidities died, as it would impact decisions on treatment planning and mitigation strategies,” Dr. Liu said.

Dr. Liu noted that controlling cardiometabolic risk factors like diabetes and hypertension is typically de-emphasized after diagnosis with early-stage lung cancer. The rationale is often that the lung cancer is a more acute concern than longer-term cardiometabolic risks. “The data from our analyses suggest a rethinking of this strategy. We need to pay more attention to controlling cardiovascular risk factors in early-stage lung cancer,” Dr. Liu said.

The findings also suggest that respiratory comorbidities should be managed more aggressively. That would allow more patients to undergo treatments like surgery and stereotactic radiation.

The Clinical Outcome Studies of the International Lung Cancer Consortium drew from two dozen studies conducted across five continents. It examined clinical, epidemiologic, genetic, and genomic factors and their potential influence on NSCLC outcomes. Cardiometabolic comorbidities included coronary artery disease, diabetes, vascular related diseases, and other heart diseases. Respiratory comorbidities included chronic obstructive pulmonary disease and asthma.

The analysis included 16,354 patients. Among patients with stage I NSCLC, there was an association between reduced overall survival (OS) and cardiometabolic comorbidity (adjusted hazard ratio, 1.17; P = .01) and respiratory comorbidity (aHR, 1.36; P < .001). For stage II/III patients, there was no significant association between OS and cardiometabolic comorbidities, but respiratory comorbidity was associated with worse OS (aHR, 1.15; P < .001). In stage 4, worse OS was associated with both cardiometabolic health comorbidity (aHR, 1.11; P = .03), but not respiratory comorbidity.

Among patients with stage IV NSCLC, there were no associations between overall survival or lung cancer–specific survival (LCSS) and respiratory or cardiometabolic risk factors. However, an examination of cause of death found a different pattern in patients with stage IB-IIIA disease: LCSS was worse among patients with respiratory comorbidities (aHR, 1.21; 95% CI, 1.09-1.34). Among those with cardiovascular comorbidities, the risk of non-NSCLC mortality was higher (aHR, 1.36; 95% CI, 1.15-1.63). The presence of respiratory comorbidity was associated with a reduced probability of undergoing surgical resection for both stage I (adjusted odds ratio, 0.45; 95% CI, 0.35-0.59) and stage II/III patients (aOR, 0.66; 95% CI, 0.53-0.80).

There was an association between non-NSCLC mortality and cardiometabolic comorbidities in stage IA (aHR, 1.37; 95% CI, 1.06-1.77) and in stages IB-IIIA (aHR, 1.32; 95% CI, 1.03-1.71) NSCLC. There were also associations between NSCLC mortality and respiratory comorbidity among stage IA (aHR, 1.51; 95% CI, 1.17-1.95) and stages IB-IIIA (aHR, 1.20; 95% CI, 1.06-1.36) NSCLC. There were no associations between respiratory comorbidity and non-NSCLC mortality.

Respiratory comorbidity was associated with a lower chance of undergoing surgical resection in stage IA (aHR, 0.54; 95% CI, 0.35-0.83) and stage IB-IIIA (aHR, 0.57; 95% CI, 0.46-0.70) cancers. Cardiometabolic comorbidity was associated with a lower rate of surgical resection only in stage 1B-3A patients (aHR, 0.73; 95% CI, 0.56-0.96). Among those who underwent resection, stage IA patients were less likely to die of lung cancer (aHR, 0.38; 95% CI, 0.28-0.52) but more likely to die of other causes (aHR, 1.73; 95% CI, 1.07-1.78). Stage IB-IIIA patients who underwent resection were less likely to die of lung cancer (aHR, 0.37; 95%, 0.32-0.42), but there was no significant association with non–lung cancer mortality.

The study was funded by the Lusi Wong Family Fund and the Alan Brown Chair. Dr. Liu has no relevant financial disclosures.

Cardiometabolic and respiratory comorbidities are associated with worse survival in patients with non–small cell lung cancer (NSCLC), and new research suggests a potential mechanism.

Prior studies had shown mixed results when it came to these comorbidities and survival, according to study coauthor author Geoffrey Liu, MD, who is an epidemiology researcher at the University of Toronto Princess Margaret Cancer Centre. The new work represents data from multiple continents, from various ethnicities and cultures.

“We found that comorbidities had much greater impact on earlier than later stages of lung cancer, consistent with this previous study,” said Dr. Liu in an email. The study was presented by Miguel Garcia-Pardo, who is a researcher at University of Toronto Princess Margaret Cancer Centre, during a poster session at the annual meeting of the European Society for Medical Oncology.

“Deaths from [cardiometabolic] comorbidities were mainly from non–lung cancer competing causes, whereas the deaths from respiratory comorbidities were primarily driven by lung cancer specific survival, i.e., deaths from lung cancer itself. We conclude that it is critical to understand how these patients with different comorbidities died, as it would impact decisions on treatment planning and mitigation strategies,” Dr. Liu said.

Dr. Liu noted that controlling cardiometabolic risk factors like diabetes and hypertension is typically de-emphasized after diagnosis with early-stage lung cancer. The rationale is often that the lung cancer is a more acute concern than longer-term cardiometabolic risks. “The data from our analyses suggest a rethinking of this strategy. We need to pay more attention to controlling cardiovascular risk factors in early-stage lung cancer,” Dr. Liu said.

The findings also suggest that respiratory comorbidities should be managed more aggressively. That would allow more patients to undergo treatments like surgery and stereotactic radiation.

The Clinical Outcome Studies of the International Lung Cancer Consortium drew from two dozen studies conducted across five continents. It examined clinical, epidemiologic, genetic, and genomic factors and their potential influence on NSCLC outcomes. Cardiometabolic comorbidities included coronary artery disease, diabetes, vascular related diseases, and other heart diseases. Respiratory comorbidities included chronic obstructive pulmonary disease and asthma.

The analysis included 16,354 patients. Among patients with stage I NSCLC, there was an association between reduced overall survival (OS) and cardiometabolic comorbidity (adjusted hazard ratio, 1.17; P = .01) and respiratory comorbidity (aHR, 1.36; P < .001). For stage II/III patients, there was no significant association between OS and cardiometabolic comorbidities, but respiratory comorbidity was associated with worse OS (aHR, 1.15; P < .001). In stage 4, worse OS was associated with both cardiometabolic health comorbidity (aHR, 1.11; P = .03), but not respiratory comorbidity.

Among patients with stage IV NSCLC, there were no associations between overall survival or lung cancer–specific survival (LCSS) and respiratory or cardiometabolic risk factors. However, an examination of cause of death found a different pattern in patients with stage IB-IIIA disease: LCSS was worse among patients with respiratory comorbidities (aHR, 1.21; 95% CI, 1.09-1.34). Among those with cardiovascular comorbidities, the risk of non-NSCLC mortality was higher (aHR, 1.36; 95% CI, 1.15-1.63). The presence of respiratory comorbidity was associated with a reduced probability of undergoing surgical resection for both stage I (adjusted odds ratio, 0.45; 95% CI, 0.35-0.59) and stage II/III patients (aOR, 0.66; 95% CI, 0.53-0.80).

There was an association between non-NSCLC mortality and cardiometabolic comorbidities in stage IA (aHR, 1.37; 95% CI, 1.06-1.77) and in stages IB-IIIA (aHR, 1.32; 95% CI, 1.03-1.71) NSCLC. There were also associations between NSCLC mortality and respiratory comorbidity among stage IA (aHR, 1.51; 95% CI, 1.17-1.95) and stages IB-IIIA (aHR, 1.20; 95% CI, 1.06-1.36) NSCLC. There were no associations between respiratory comorbidity and non-NSCLC mortality.

Respiratory comorbidity was associated with a lower chance of undergoing surgical resection in stage IA (aHR, 0.54; 95% CI, 0.35-0.83) and stage IB-IIIA (aHR, 0.57; 95% CI, 0.46-0.70) cancers. Cardiometabolic comorbidity was associated with a lower rate of surgical resection only in stage 1B-3A patients (aHR, 0.73; 95% CI, 0.56-0.96). Among those who underwent resection, stage IA patients were less likely to die of lung cancer (aHR, 0.38; 95% CI, 0.28-0.52) but more likely to die of other causes (aHR, 1.73; 95% CI, 1.07-1.78). Stage IB-IIIA patients who underwent resection were less likely to die of lung cancer (aHR, 0.37; 95%, 0.32-0.42), but there was no significant association with non–lung cancer mortality.

The study was funded by the Lusi Wong Family Fund and the Alan Brown Chair. Dr. Liu has no relevant financial disclosures.