General Thoracic

Progression free survival was significantly better in unresectable stage 3 non–small cell lung cancer when patients were treated with durvalumab in combination with other immunotherapies, instead of durvalumab alone, following chemoradiotherapy.

Both combinations – durvalumab plus either the anti-CD73 monoclonal antibody oleclumab or the anti-NKG2A mAb monalizumab – also numerically improved objective response rate. “Safety profiles were consistent across arms and no new safety signals were identified,” said Alexandre Martinez-Marti, MD, the lead investigator on the phase 2 trial, dubbed COAST, which he presented (abstract LBA42) at the 2021 European Society for Medical Oncology Congress on Sept. 17.

“These data support further evaluations of these combinations,” said Dr. Martinez-Marti, also a thoracic medical oncologist at the Vall d’Hebron Institute of Oncology in Barcelona.

Durvalumab is already established as a standard of care option for patients with unresectable stage 3 NSCLC who don’t progress after concurrent chemoradiation. There’s been preliminary data suggesting the benefits might be greater with oleclumab or monalizumab, so the study team looked into the issue.

They randomized 66 patients with unresectable stage 3 NSCLC and no progression after chemoradiotherapy to durvalumab 1,500 mg IV every 4 weeks; 59 others to durvalumab at the same dosage plus oleclumab 3,000 mg IV every 2 weeks for the first two cycles then every 4 weeks, and 61 were randomized to durvalumab plus monalizumab 750 mg IV every 2 weeks.

Patients were treated for up to 12 months, and they started treatment no later than 42 days after completing chemoradiation.

Over a median follow-up of 11.5 months, median progression-free survival (PFS) was 6.3 months in the durvalumab arm, but 15.1 months with the monalizumab combination (PFS hazard ratio versus durvalumab alone, 0.65; 95% CI, 0.49-0.85), and not reached in the oleclumab arm (PFS HR, 0.44; 95% CI, 0.26-0.75).

There were only a few complete responders across the study groups. Partial responses rates were 22.4% of the durvalumab alone arm, 36.7% in the oleclumab group, and 32.3% in the monalizumab arm.

The investigator assessed objective response rate was 25.4% with durvalumab alone, 38.3% in the oleclumab group, and 37.1% with the monalizumab combination. Curves started to separate from durvalumab monotherapy at around 2-4 months.

“Overall, the safety profiles of the two combinations were generally similar to the safety profile of durvalumab alone,” Dr. Martinez-Marti said. The rate of grade 3 or higher treatment-emergent events incidence was 39.4% with durvalumab, 40.7% the oleclumab combination, and 27.9% with monalizumab.

The most common grade 3/4 events were pneumonia (5.9%) and decreased lymphocyte count (3.2%); both were less common with the monalizumab combination.

Combined rates of pneumonitis and radiation pneumonitis of any grade were 21.2% with durvalumab, 28.8% in the oleclumab group, and 21.3% with monalizumab.

The groups were generally well balanced at baseline. The majority of subjects were men, White, and former smokers. Most subjects had stage 3A or 3B disease.

The work was funded by AstraZeneca. The investigators disclosed numerous ties to the company, including Dr. Martinez-Marti, who reported personal fees, travel expenses, and other connections.

This article was updated 9/24/21.

aotto@mdedge.com

Progression free survival was significantly better in unresectable stage 3 non–small cell lung cancer when patients were treated with durvalumab in combination with other immunotherapies, instead of durvalumab alone, following chemoradiotherapy.

Both combinations – durvalumab plus either the anti-CD73 monoclonal antibody oleclumab or the anti-NKG2A mAb monalizumab – also numerically improved objective response rate. “Safety profiles were consistent across arms and no new safety signals were identified,” said Alexandre Martinez-Marti, MD, the lead investigator on the phase 2 trial, dubbed COAST, which he presented (abstract LBA42) at the 2021 European Society for Medical Oncology Congress on Sept. 17.

“These data support further evaluations of these combinations,” said Dr. Martinez-Marti, also a thoracic medical oncologist at the Vall d’Hebron Institute of Oncology in Barcelona.

Durvalumab is already established as a standard of care option for patients with unresectable stage 3 NSCLC who don’t progress after concurrent chemoradiation. There’s been preliminary data suggesting the benefits might be greater with oleclumab or monalizumab, so the study team looked into the issue.

They randomized 66 patients with unresectable stage 3 NSCLC and no progression after chemoradiotherapy to durvalumab 1,500 mg IV every 4 weeks; 59 others to durvalumab at the same dosage plus oleclumab 3,000 mg IV every 2 weeks for the first two cycles then every 4 weeks, and 61 were randomized to durvalumab plus monalizumab 750 mg IV every 2 weeks.

Patients were treated for up to 12 months, and they started treatment no later than 42 days after completing chemoradiation.

Over a median follow-up of 11.5 months, median progression-free survival (PFS) was 6.3 months in the durvalumab arm, but 15.1 months with the monalizumab combination (PFS hazard ratio versus durvalumab alone, 0.65; 95% CI, 0.49-0.85), and not reached in the oleclumab arm (PFS HR, 0.44; 95% CI, 0.26-0.75).

There were only a few complete responders across the study groups. Partial responses rates were 22.4% of the durvalumab alone arm, 36.7% in the oleclumab group, and 32.3% in the monalizumab arm.

The investigator assessed objective response rate was 25.4% with durvalumab alone, 38.3% in the oleclumab group, and 37.1% with the monalizumab combination. Curves started to separate from durvalumab monotherapy at around 2-4 months.

“Overall, the safety profiles of the two combinations were generally similar to the safety profile of durvalumab alone,” Dr. Martinez-Marti said. The rate of grade 3 or higher treatment-emergent events incidence was 39.4% with durvalumab, 40.7% the oleclumab combination, and 27.9% with monalizumab.

The most common grade 3/4 events were pneumonia (5.9%) and decreased lymphocyte count (3.2%); both were less common with the monalizumab combination.

Combined rates of pneumonitis and radiation pneumonitis of any grade were 21.2% with durvalumab, 28.8% in the oleclumab group, and 21.3% with monalizumab.

The groups were generally well balanced at baseline. The majority of subjects were men, White, and former smokers. Most subjects had stage 3A or 3B disease.

The work was funded by AstraZeneca. The investigators disclosed numerous ties to the company, including Dr. Martinez-Marti, who reported personal fees, travel expenses, and other connections.

This article was updated 9/24/21.

aotto@mdedge.com

Progression free survival was significantly better in unresectable stage 3 non–small cell lung cancer when patients were treated with durvalumab in combination with other immunotherapies, instead of durvalumab alone, following chemoradiotherapy.

Both combinations – durvalumab plus either the anti-CD73 monoclonal antibody oleclumab or the anti-NKG2A mAb monalizumab – also numerically improved objective response rate. “Safety profiles were consistent across arms and no new safety signals were identified,” said Alexandre Martinez-Marti, MD, the lead investigator on the phase 2 trial, dubbed COAST, which he presented (abstract LBA42) at the 2021 European Society for Medical Oncology Congress on Sept. 17.

“These data support further evaluations of these combinations,” said Dr. Martinez-Marti, also a thoracic medical oncologist at the Vall d’Hebron Institute of Oncology in Barcelona.

Durvalumab is already established as a standard of care option for patients with unresectable stage 3 NSCLC who don’t progress after concurrent chemoradiation. There’s been preliminary data suggesting the benefits might be greater with oleclumab or monalizumab, so the study team looked into the issue.

They randomized 66 patients with unresectable stage 3 NSCLC and no progression after chemoradiotherapy to durvalumab 1,500 mg IV every 4 weeks; 59 others to durvalumab at the same dosage plus oleclumab 3,000 mg IV every 2 weeks for the first two cycles then every 4 weeks, and 61 were randomized to durvalumab plus monalizumab 750 mg IV every 2 weeks.

Patients were treated for up to 12 months, and they started treatment no later than 42 days after completing chemoradiation.

Over a median follow-up of 11.5 months, median progression-free survival (PFS) was 6.3 months in the durvalumab arm, but 15.1 months with the monalizumab combination (PFS hazard ratio versus durvalumab alone, 0.65; 95% CI, 0.49-0.85), and not reached in the oleclumab arm (PFS HR, 0.44; 95% CI, 0.26-0.75).

There were only a few complete responders across the study groups. Partial responses rates were 22.4% of the durvalumab alone arm, 36.7% in the oleclumab group, and 32.3% in the monalizumab arm.

The investigator assessed objective response rate was 25.4% with durvalumab alone, 38.3% in the oleclumab group, and 37.1% with the monalizumab combination. Curves started to separate from durvalumab monotherapy at around 2-4 months.

“Overall, the safety profiles of the two combinations were generally similar to the safety profile of durvalumab alone,” Dr. Martinez-Marti said. The rate of grade 3 or higher treatment-emergent events incidence was 39.4% with durvalumab, 40.7% the oleclumab combination, and 27.9% with monalizumab.

The most common grade 3/4 events were pneumonia (5.9%) and decreased lymphocyte count (3.2%); both were less common with the monalizumab combination.

Combined rates of pneumonitis and radiation pneumonitis of any grade were 21.2% with durvalumab, 28.8% in the oleclumab group, and 21.3% with monalizumab.

The groups were generally well balanced at baseline. The majority of subjects were men, White, and former smokers. Most subjects had stage 3A or 3B disease.

The work was funded by AstraZeneca. The investigators disclosed numerous ties to the company, including Dr. Martinez-Marti, who reported personal fees, travel expenses, and other connections.

This article was updated 9/24/21.

aotto@mdedge.com

While postoperative conformal radiotherapy (PORT) reduces the risk of mediastinal relapse in completely resected non–small cell lung cancer with mediastinal nodal metastases (N2), it does not have a significant impact on disease-free and overall survival, according to a report (abstract 1170O) recently presented at the 2021 European Society for Medical Oncology Congress on Sept. 17.

The report was an update on the LungART international clinical trial, which, at the 2020 ESMO meeting, was shown not to improve disease-free survival over the course of 3 years. The update showed that, in addition to the lack of disease-free survival benefit, there was also no difference in metastases, and patients randomized to PORT had higher rates of death and grade 3/4 cardiopulmonary toxicity. The investigators returned this year to expand on another finding from the trial, a 51% reduction in the risk of mediastinal relapse with postoperative radiotherapy. The new analysis suggests there might still be a role for PORT in select patients, perhaps those with heavy nodal involvement, said lead investigator and presenter Cecile Le Pechoux, MD, radiation oncologist at the Gustave Roussy cancer treatment center in Villejuif, France.

For now, “personalized prescription of PORT should be based on prognostic factors of relapse and joint assessment of toxicity and efficacy,” she said.

Study discussant Pilar Garrido, MD, PhD, head of thoracic tumors Ramon y Cajal University Hospital, Madrid, agreed that there might still be a benefit for people with multiple N2 nodal station involvement, but at present, she said, “for me PORT cannot be the standard of care ... given the toxicity and mortality among PORT patients in LungART.”

The trial randomized 501 patients with non–small cell lung cancer with mediastinal involvement to either PORT at 54 Gy over 5.5 weeks or no further treatment following complete resection. Neoadjuvant or adjuvant chemotherapy were allowed.

The 3-year mediastinal relapse-free survival was 72.26% in the control arm but 86.06% with PORT (hazard ratio, 0.45; 95% confidence interval, 0.3-0.69).

“There is a significant difference” when it comes to mediastinal relapse, and “patients who have PORT do better. If we look at the location of mediastinal relapse, most [patients] relapse within the initially involved node. This is important information,” Dr. Le Pechoux said.

For left-sided tumors, the most frequent sites of mediastinal relapse were thoracic lymph node stations 7, 4L, and 4R. For right sided tumors, the most frequent stations were 4R, 2R and 7.

Prognostic factors for disease-free survival included quality of resection, extent of mediastinal involvement, and lymph node ratio (involved/explored). Nodal involvement was a significant prognostic factor for overall survival, but PORT was not (HR, 0.98; 95% CI, 0.7-1.4).

Mediastinal involvement with more than two node stations and less than an RO, or microscopically margin-negative resection, increased the risk of relapse.

The work was funded by the French National Cancer Institute, French Health Ministry, Institute Gustave Roussy, and Cancer Research UK. Dr. Pechoux and Dr. Garido disclosed ties to AstraZeneca, Roche, Amgen, and other companies.

This article was updated 9/24/21.

aotto@mdedge.com

While postoperative conformal radiotherapy (PORT) reduces the risk of mediastinal relapse in completely resected non–small cell lung cancer with mediastinal nodal metastases (N2), it does not have a significant impact on disease-free and overall survival, according to a report (abstract 1170O) recently presented at the 2021 European Society for Medical Oncology Congress on Sept. 17.

The report was an update on the LungART international clinical trial, which, at the 2020 ESMO meeting, was shown not to improve disease-free survival over the course of 3 years. The update showed that, in addition to the lack of disease-free survival benefit, there was also no difference in metastases, and patients randomized to PORT had higher rates of death and grade 3/4 cardiopulmonary toxicity. The investigators returned this year to expand on another finding from the trial, a 51% reduction in the risk of mediastinal relapse with postoperative radiotherapy. The new analysis suggests there might still be a role for PORT in select patients, perhaps those with heavy nodal involvement, said lead investigator and presenter Cecile Le Pechoux, MD, radiation oncologist at the Gustave Roussy cancer treatment center in Villejuif, France.

For now, “personalized prescription of PORT should be based on prognostic factors of relapse and joint assessment of toxicity and efficacy,” she said.

Study discussant Pilar Garrido, MD, PhD, head of thoracic tumors Ramon y Cajal University Hospital, Madrid, agreed that there might still be a benefit for people with multiple N2 nodal station involvement, but at present, she said, “for me PORT cannot be the standard of care ... given the toxicity and mortality among PORT patients in LungART.”

The trial randomized 501 patients with non–small cell lung cancer with mediastinal involvement to either PORT at 54 Gy over 5.5 weeks or no further treatment following complete resection. Neoadjuvant or adjuvant chemotherapy were allowed.

The 3-year mediastinal relapse-free survival was 72.26% in the control arm but 86.06% with PORT (hazard ratio, 0.45; 95% confidence interval, 0.3-0.69).

“There is a significant difference” when it comes to mediastinal relapse, and “patients who have PORT do better. If we look at the location of mediastinal relapse, most [patients] relapse within the initially involved node. This is important information,” Dr. Le Pechoux said.

For left-sided tumors, the most frequent sites of mediastinal relapse were thoracic lymph node stations 7, 4L, and 4R. For right sided tumors, the most frequent stations were 4R, 2R and 7.

Prognostic factors for disease-free survival included quality of resection, extent of mediastinal involvement, and lymph node ratio (involved/explored). Nodal involvement was a significant prognostic factor for overall survival, but PORT was not (HR, 0.98; 95% CI, 0.7-1.4).

Mediastinal involvement with more than two node stations and less than an RO, or microscopically margin-negative resection, increased the risk of relapse.

The work was funded by the French National Cancer Institute, French Health Ministry, Institute Gustave Roussy, and Cancer Research UK. Dr. Pechoux and Dr. Garido disclosed ties to AstraZeneca, Roche, Amgen, and other companies.

This article was updated 9/24/21.

aotto@mdedge.com

While postoperative conformal radiotherapy (PORT) reduces the risk of mediastinal relapse in completely resected non–small cell lung cancer with mediastinal nodal metastases (N2), it does not have a significant impact on disease-free and overall survival, according to a report (abstract 1170O) recently presented at the 2021 European Society for Medical Oncology Congress on Sept. 17.

The report was an update on the LungART international clinical trial, which, at the 2020 ESMO meeting, was shown not to improve disease-free survival over the course of 3 years. The update showed that, in addition to the lack of disease-free survival benefit, there was also no difference in metastases, and patients randomized to PORT had higher rates of death and grade 3/4 cardiopulmonary toxicity. The investigators returned this year to expand on another finding from the trial, a 51% reduction in the risk of mediastinal relapse with postoperative radiotherapy. The new analysis suggests there might still be a role for PORT in select patients, perhaps those with heavy nodal involvement, said lead investigator and presenter Cecile Le Pechoux, MD, radiation oncologist at the Gustave Roussy cancer treatment center in Villejuif, France.

For now, “personalized prescription of PORT should be based on prognostic factors of relapse and joint assessment of toxicity and efficacy,” she said.

Study discussant Pilar Garrido, MD, PhD, head of thoracic tumors Ramon y Cajal University Hospital, Madrid, agreed that there might still be a benefit for people with multiple N2 nodal station involvement, but at present, she said, “for me PORT cannot be the standard of care ... given the toxicity and mortality among PORT patients in LungART.”

The trial randomized 501 patients with non–small cell lung cancer with mediastinal involvement to either PORT at 54 Gy over 5.5 weeks or no further treatment following complete resection. Neoadjuvant or adjuvant chemotherapy were allowed.

The 3-year mediastinal relapse-free survival was 72.26% in the control arm but 86.06% with PORT (hazard ratio, 0.45; 95% confidence interval, 0.3-0.69).

“There is a significant difference” when it comes to mediastinal relapse, and “patients who have PORT do better. If we look at the location of mediastinal relapse, most [patients] relapse within the initially involved node. This is important information,” Dr. Le Pechoux said.

For left-sided tumors, the most frequent sites of mediastinal relapse were thoracic lymph node stations 7, 4L, and 4R. For right sided tumors, the most frequent stations were 4R, 2R and 7.

Prognostic factors for disease-free survival included quality of resection, extent of mediastinal involvement, and lymph node ratio (involved/explored). Nodal involvement was a significant prognostic factor for overall survival, but PORT was not (HR, 0.98; 95% CI, 0.7-1.4).

Mediastinal involvement with more than two node stations and less than an RO, or microscopically margin-negative resection, increased the risk of relapse.

The work was funded by the French National Cancer Institute, French Health Ministry, Institute Gustave Roussy, and Cancer Research UK. Dr. Pechoux and Dr. Garido disclosed ties to AstraZeneca, Roche, Amgen, and other companies.

This article was updated 9/24/21.

aotto@mdedge.com

TORONTO – The implanted phrenic-nerve stimulation device that received Food and Drug Administration marketing approval in October 2017 for treating central sleep apnea has now shown safety and efficacy out to 18 months of continuous use in 102 patients.

After 18 months of treatment with the Remede System, patients’ outcomes remained stable and patients continued to see the improvements they had experienced after 6 and 12 months of treatment. These improvements included significant average reductions from baseline in apnea-hypopnea index and central apnea index and significant increases in oxygenation and sleep quality, Andrew C. Kao, MD, said at the CHEST annual meeting.

Mitchel L. Zoler/Frontline Medical News

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

TORONTO – The implanted phrenic-nerve stimulation device that received Food and Drug Administration marketing approval in October 2017 for treating central sleep apnea has now shown safety and efficacy out to 18 months of continuous use in 102 patients.

After 18 months of treatment with the Remede System, patients’ outcomes remained stable and patients continued to see the improvements they had experienced after 6 and 12 months of treatment. These improvements included significant average reductions from baseline in apnea-hypopnea index and central apnea index and significant increases in oxygenation and sleep quality, Andrew C. Kao, MD, said at the CHEST annual meeting.

Mitchel L. Zoler/Frontline Medical News

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

TORONTO – The implanted phrenic-nerve stimulation device that received Food and Drug Administration marketing approval in October 2017 for treating central sleep apnea has now shown safety and efficacy out to 18 months of continuous use in 102 patients.

After 18 months of treatment with the Remede System, patients’ outcomes remained stable and patients continued to see the improvements they had experienced after 6 and 12 months of treatment. These improvements included significant average reductions from baseline in apnea-hypopnea index and central apnea index and significant increases in oxygenation and sleep quality, Andrew C. Kao, MD, said at the CHEST annual meeting.

Mitchel L. Zoler/Frontline Medical News

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

WASHINGTON – In patients with epilepsy, treatment of obstructive sleep apnea with continuous positive airway pressure may lead to substantial and sustained reductions in seizure activity, according to data presented at the annual meeting of the American Epilepsy Society.

The reduction in seizure activity with continuous positive airway pressure (cPAP) in patients with epilepsy contributes to other evidence that poor sleep quality is an important but preventable risk factor for seizures, according to Thapanee Somboon, MD, a research fellow at the Sleep Disorders Center at the Cleveland Clinic in Ohio.

Ted Bosworth/Frontline Medical News

Dr. Somboon reported no financial relationships relevant to the study.

WASHINGTON – In patients with epilepsy, treatment of obstructive sleep apnea with continuous positive airway pressure may lead to substantial and sustained reductions in seizure activity, according to data presented at the annual meeting of the American Epilepsy Society.

The reduction in seizure activity with continuous positive airway pressure (cPAP) in patients with epilepsy contributes to other evidence that poor sleep quality is an important but preventable risk factor for seizures, according to Thapanee Somboon, MD, a research fellow at the Sleep Disorders Center at the Cleveland Clinic in Ohio.

Ted Bosworth/Frontline Medical News

Dr. Somboon reported no financial relationships relevant to the study.

WASHINGTON – In patients with epilepsy, treatment of obstructive sleep apnea with continuous positive airway pressure may lead to substantial and sustained reductions in seizure activity, according to data presented at the annual meeting of the American Epilepsy Society.

The reduction in seizure activity with continuous positive airway pressure (cPAP) in patients with epilepsy contributes to other evidence that poor sleep quality is an important but preventable risk factor for seizures, according to Thapanee Somboon, MD, a research fellow at the Sleep Disorders Center at the Cleveland Clinic in Ohio.

Ted Bosworth/Frontline Medical News

Dr. Somboon reported no financial relationships relevant to the study.

NATIONAL HARBOR, MD. – Combination treatment with the first-in-class glutaminase inhibitor CB-839 and nivolumab is well-tolerated and shows clinical activity in patients with advanced melanoma, renal cell carcinoma, or non-small cell lung cancer, including anti-PD-1/PD-L1 refractory patients, according to initial results from a phase 1/2 study.

Responses in melanoma patients who were progressing on nivolumab at study entry and who were refractory to multiple prior immunotherapy regimens are particularly notable, as they highlight the potential for CB-839, when added to nivolumab (Opdivo), to help overcome resistance to anti-PD-L1 therapy, Funda Meric‐Bernstam, MD, reported at the annual meeting of the Society for Immunotherapy of Cancer.

CB‐839 is highly selective and targets tumor glutamine metabolism, said Dr. Meric-Bernstam of the University of Texas MD Anderson Cancer Center, Houston.

Competition between tumor cells and immune cells for nutrients such as glutamine in the tumor microenvironment can create a metabolic checkpoint that induces local immune suppression. CB‐839 inhibits tumor glutamine consumption, thereby increasing glutamine availability to support T‐cell activity, she explained, noting that in preclinical models, CB‐839 increased intra‐tumoral glutamine and enhanced antitumor activity of PD‐1/PD‐L1 inhibitors.

In the phase 1 dose escalation study, she and her colleagues evaluated the safety and efficacy of CB-839 in combination with the PD‐1 inhibitor nivolumab in patients with melanoma, non-small cell lung cancer (NSCLC), or renal cell carcinoma (RCC). Phase 2 expansion cohorts include a melanoma rescue cohort of patients progressing on anti-PD-L1 therapy at study entry (22 patients), an NSCLC and RCC rescue cohort of patients who were progressing on anti-PD-L1 therapy at study entry or who had stable disease for 6 months or longer without a response (11 NSCLC and 11 RCC), an RCC cohort of patients with prior immunotherapy exposure and no response (10 patients), and an RCC cohort of patents who had no prior immunotherapy exposure (28 patients).

During dose escalation, patients received oral CB‐839 at 600 mg or 800 mg twice daily in combination with standard‐dose nivolumab. In the ongoing phase 2 expansion study, which continues to enroll, patients are receiving 800 mg of CB-839 twice daily with standard‐dose nivolumab, Dr. Meric-Bernstam said.

Patients in each of the cohorts were high risk and/or had intermediate or poor prognostic status at study entry. For example, 50% of patients in the melanoma rescue cohort had liver metastases, 77% had other visceral metastases, and 18% had brain metastases, and the majority of patients in the lung cancer/RCC cohort had visceral metastases. Most had progressive disease as their best response on their last line of immunotherapy.

Of 16 response-evaluable melanoma patients, 1 experienced a complete response, 2 had partial responses, and 4 had stable disease.

“So overall in this patient population that was progressing on a PD-1/PD-L1 inhibitor at enrollment, 19% had an objective response. The disease control rate in this group was 44%,” she said.

In evaluable patients in the lung cancer rescue cohort (6 patients), RCC rescue cohort (8 patients), and RCC prior exposure cohort (7 patients), disease control rates ranged from 57% to 75%, and in the immunotherapy-naive RCC cohort (19 patients), the partial response rate was 21%, and 53% had stable disease, so the overall disease control rate was 74%. Half of the patients in that group remain on study, she noted.

A closer look at the melanoma rescue cohort showed dramatic and rapid responses in two patients who each achieved a partial response in about 8 weeks with response durations of 3.7 months and 5.4 months, respectively. Additionally, pre-treatment biopsies in this cohort showed an elevated T-cell inflamed signature associated with clinical benefit from the addition of CB-839, and in one patient who had both a pretreatment and on-treatment biopsy that was evaluable, the latter showed an increase in T-cell inflamed signature and T-cell effector genes.

In all cohorts, the combination therapy was generally well tolerated. A maximum tolerated dose was not reached. Dose-limiting toxicity – a grade 3 alanine aminotransferase (ALT) increase – occurred in one patient on the 800-mg dose. The most common grade 3 or greater adverse events were fatigue, nausea, photophobia, rash, and elevated ALT, she said, noting that two patients discontinued for treatment-related adverse events (one for a grade 3 rash and one for grade 2 pneumonitis).

“Overall there appeared to be no apparent increase in immune-related adverse events, either in rate or severity, compared with [nivolumab] monotherapy,” she said.

The combination of CB-839 and nivolumab was well tolerated, and in some patients – as seen in the melanoma cohort – adding CB-839 to checkpoint blockade can overcome checkpoint blockade resistance, Dr. Meric-Bernstam concluded, noting that the disease control rates seen in the majority of lung cancer and RCC patients who were progressing on checkpoint blockade is encouraging, as is the objective response rate seen thus far in the RCC therapy-naive patients, and the stable and deep responses seen in the melanoma rescue cohort.

“Based on our encouraging signal in the melanoma rescue cohort, this [cohort] has been expanded,” she said.

Calithera Biosciences sponsored the study. Bristol-Myers Squibb provided nivolumab for the study. Dr. Meric-Bernstam has received grant or research support from Calithera Biosciences and many other companies. She also reported being a paid consultant for several companies and serving on an advisory committee or review panel, or as a board member for multiple companies.

sworcester@frontlinemedcom.com

NATIONAL HARBOR, MD. – Combination treatment with the first-in-class glutaminase inhibitor CB-839 and nivolumab is well-tolerated and shows clinical activity in patients with advanced melanoma, renal cell carcinoma, or non-small cell lung cancer, including anti-PD-1/PD-L1 refractory patients, according to initial results from a phase 1/2 study.

Responses in melanoma patients who were progressing on nivolumab at study entry and who were refractory to multiple prior immunotherapy regimens are particularly notable, as they highlight the potential for CB-839, when added to nivolumab (Opdivo), to help overcome resistance to anti-PD-L1 therapy, Funda Meric‐Bernstam, MD, reported at the annual meeting of the Society for Immunotherapy of Cancer.

CB‐839 is highly selective and targets tumor glutamine metabolism, said Dr. Meric-Bernstam of the University of Texas MD Anderson Cancer Center, Houston.

Competition between tumor cells and immune cells for nutrients such as glutamine in the tumor microenvironment can create a metabolic checkpoint that induces local immune suppression. CB‐839 inhibits tumor glutamine consumption, thereby increasing glutamine availability to support T‐cell activity, she explained, noting that in preclinical models, CB‐839 increased intra‐tumoral glutamine and enhanced antitumor activity of PD‐1/PD‐L1 inhibitors.

In the phase 1 dose escalation study, she and her colleagues evaluated the safety and efficacy of CB-839 in combination with the PD‐1 inhibitor nivolumab in patients with melanoma, non-small cell lung cancer (NSCLC), or renal cell carcinoma (RCC). Phase 2 expansion cohorts include a melanoma rescue cohort of patients progressing on anti-PD-L1 therapy at study entry (22 patients), an NSCLC and RCC rescue cohort of patients who were progressing on anti-PD-L1 therapy at study entry or who had stable disease for 6 months or longer without a response (11 NSCLC and 11 RCC), an RCC cohort of patients with prior immunotherapy exposure and no response (10 patients), and an RCC cohort of patents who had no prior immunotherapy exposure (28 patients).

During dose escalation, patients received oral CB‐839 at 600 mg or 800 mg twice daily in combination with standard‐dose nivolumab. In the ongoing phase 2 expansion study, which continues to enroll, patients are receiving 800 mg of CB-839 twice daily with standard‐dose nivolumab, Dr. Meric-Bernstam said.

Patients in each of the cohorts were high risk and/or had intermediate or poor prognostic status at study entry. For example, 50% of patients in the melanoma rescue cohort had liver metastases, 77% had other visceral metastases, and 18% had brain metastases, and the majority of patients in the lung cancer/RCC cohort had visceral metastases. Most had progressive disease as their best response on their last line of immunotherapy.

Of 16 response-evaluable melanoma patients, 1 experienced a complete response, 2 had partial responses, and 4 had stable disease.

“So overall in this patient population that was progressing on a PD-1/PD-L1 inhibitor at enrollment, 19% had an objective response. The disease control rate in this group was 44%,” she said.

In evaluable patients in the lung cancer rescue cohort (6 patients), RCC rescue cohort (8 patients), and RCC prior exposure cohort (7 patients), disease control rates ranged from 57% to 75%, and in the immunotherapy-naive RCC cohort (19 patients), the partial response rate was 21%, and 53% had stable disease, so the overall disease control rate was 74%. Half of the patients in that group remain on study, she noted.

A closer look at the melanoma rescue cohort showed dramatic and rapid responses in two patients who each achieved a partial response in about 8 weeks with response durations of 3.7 months and 5.4 months, respectively. Additionally, pre-treatment biopsies in this cohort showed an elevated T-cell inflamed signature associated with clinical benefit from the addition of CB-839, and in one patient who had both a pretreatment and on-treatment biopsy that was evaluable, the latter showed an increase in T-cell inflamed signature and T-cell effector genes.

In all cohorts, the combination therapy was generally well tolerated. A maximum tolerated dose was not reached. Dose-limiting toxicity – a grade 3 alanine aminotransferase (ALT) increase – occurred in one patient on the 800-mg dose. The most common grade 3 or greater adverse events were fatigue, nausea, photophobia, rash, and elevated ALT, she said, noting that two patients discontinued for treatment-related adverse events (one for a grade 3 rash and one for grade 2 pneumonitis).

“Overall there appeared to be no apparent increase in immune-related adverse events, either in rate or severity, compared with [nivolumab] monotherapy,” she said.

The combination of CB-839 and nivolumab was well tolerated, and in some patients – as seen in the melanoma cohort – adding CB-839 to checkpoint blockade can overcome checkpoint blockade resistance, Dr. Meric-Bernstam concluded, noting that the disease control rates seen in the majority of lung cancer and RCC patients who were progressing on checkpoint blockade is encouraging, as is the objective response rate seen thus far in the RCC therapy-naive patients, and the stable and deep responses seen in the melanoma rescue cohort.

“Based on our encouraging signal in the melanoma rescue cohort, this [cohort] has been expanded,” she said.

Calithera Biosciences sponsored the study. Bristol-Myers Squibb provided nivolumab for the study. Dr. Meric-Bernstam has received grant or research support from Calithera Biosciences and many other companies. She also reported being a paid consultant for several companies and serving on an advisory committee or review panel, or as a board member for multiple companies.

sworcester@frontlinemedcom.com

NATIONAL HARBOR, MD. – Combination treatment with the first-in-class glutaminase inhibitor CB-839 and nivolumab is well-tolerated and shows clinical activity in patients with advanced melanoma, renal cell carcinoma, or non-small cell lung cancer, including anti-PD-1/PD-L1 refractory patients, according to initial results from a phase 1/2 study.

Responses in melanoma patients who were progressing on nivolumab at study entry and who were refractory to multiple prior immunotherapy regimens are particularly notable, as they highlight the potential for CB-839, when added to nivolumab (Opdivo), to help overcome resistance to anti-PD-L1 therapy, Funda Meric‐Bernstam, MD, reported at the annual meeting of the Society for Immunotherapy of Cancer.

CB‐839 is highly selective and targets tumor glutamine metabolism, said Dr. Meric-Bernstam of the University of Texas MD Anderson Cancer Center, Houston.

Competition between tumor cells and immune cells for nutrients such as glutamine in the tumor microenvironment can create a metabolic checkpoint that induces local immune suppression. CB‐839 inhibits tumor glutamine consumption, thereby increasing glutamine availability to support T‐cell activity, she explained, noting that in preclinical models, CB‐839 increased intra‐tumoral glutamine and enhanced antitumor activity of PD‐1/PD‐L1 inhibitors.

In the phase 1 dose escalation study, she and her colleagues evaluated the safety and efficacy of CB-839 in combination with the PD‐1 inhibitor nivolumab in patients with melanoma, non-small cell lung cancer (NSCLC), or renal cell carcinoma (RCC). Phase 2 expansion cohorts include a melanoma rescue cohort of patients progressing on anti-PD-L1 therapy at study entry (22 patients), an NSCLC and RCC rescue cohort of patients who were progressing on anti-PD-L1 therapy at study entry or who had stable disease for 6 months or longer without a response (11 NSCLC and 11 RCC), an RCC cohort of patients with prior immunotherapy exposure and no response (10 patients), and an RCC cohort of patents who had no prior immunotherapy exposure (28 patients).

During dose escalation, patients received oral CB‐839 at 600 mg or 800 mg twice daily in combination with standard‐dose nivolumab. In the ongoing phase 2 expansion study, which continues to enroll, patients are receiving 800 mg of CB-839 twice daily with standard‐dose nivolumab, Dr. Meric-Bernstam said.

Patients in each of the cohorts were high risk and/or had intermediate or poor prognostic status at study entry. For example, 50% of patients in the melanoma rescue cohort had liver metastases, 77% had other visceral metastases, and 18% had brain metastases, and the majority of patients in the lung cancer/RCC cohort had visceral metastases. Most had progressive disease as their best response on their last line of immunotherapy.

Of 16 response-evaluable melanoma patients, 1 experienced a complete response, 2 had partial responses, and 4 had stable disease.

“So overall in this patient population that was progressing on a PD-1/PD-L1 inhibitor at enrollment, 19% had an objective response. The disease control rate in this group was 44%,” she said.

In evaluable patients in the lung cancer rescue cohort (6 patients), RCC rescue cohort (8 patients), and RCC prior exposure cohort (7 patients), disease control rates ranged from 57% to 75%, and in the immunotherapy-naive RCC cohort (19 patients), the partial response rate was 21%, and 53% had stable disease, so the overall disease control rate was 74%. Half of the patients in that group remain on study, she noted.

A closer look at the melanoma rescue cohort showed dramatic and rapid responses in two patients who each achieved a partial response in about 8 weeks with response durations of 3.7 months and 5.4 months, respectively. Additionally, pre-treatment biopsies in this cohort showed an elevated T-cell inflamed signature associated with clinical benefit from the addition of CB-839, and in one patient who had both a pretreatment and on-treatment biopsy that was evaluable, the latter showed an increase in T-cell inflamed signature and T-cell effector genes.

In all cohorts, the combination therapy was generally well tolerated. A maximum tolerated dose was not reached. Dose-limiting toxicity – a grade 3 alanine aminotransferase (ALT) increase – occurred in one patient on the 800-mg dose. The most common grade 3 or greater adverse events were fatigue, nausea, photophobia, rash, and elevated ALT, she said, noting that two patients discontinued for treatment-related adverse events (one for a grade 3 rash and one for grade 2 pneumonitis).

“Overall there appeared to be no apparent increase in immune-related adverse events, either in rate or severity, compared with [nivolumab] monotherapy,” she said.

The combination of CB-839 and nivolumab was well tolerated, and in some patients – as seen in the melanoma cohort – adding CB-839 to checkpoint blockade can overcome checkpoint blockade resistance, Dr. Meric-Bernstam concluded, noting that the disease control rates seen in the majority of lung cancer and RCC patients who were progressing on checkpoint blockade is encouraging, as is the objective response rate seen thus far in the RCC therapy-naive patients, and the stable and deep responses seen in the melanoma rescue cohort.

“Based on our encouraging signal in the melanoma rescue cohort, this [cohort] has been expanded,” she said.

Calithera Biosciences sponsored the study. Bristol-Myers Squibb provided nivolumab for the study. Dr. Meric-Bernstam has received grant or research support from Calithera Biosciences and many other companies. She also reported being a paid consultant for several companies and serving on an advisory committee or review panel, or as a board member for multiple companies.

sworcester@frontlinemedcom.com

NATIONAL HARBOR, MD. – The oral, class I selective histone deacetylase (HDAC) inhibitor entinostat given in combination with pembrolizumab demonstrated antitumor activity and acceptable safety in patients with non–small cell lung cancer in the phase 1b/2 ENCORE 601 study.

Entinostat, which has been shown in preclinical models to enhance suppressor cells in the tumor microenvironment, was evaluated in ENCORE 601 as a treatment for non–small cell lung cancer (NSCLC), melanoma, and colorectal cancer. Previously reported phase 1 results showed that an oral dose of 5 mg weekly plus 200 mg of pembrolizumab given intravenously every 3 weeks deserved further exploration for these indications, according to Leena Gandhi, MD, who reported phase 2, stage 1 results from the lung cancer arm of the Simon two-stage study at the annual meeting of the Society for Immunotherapy of Cancer.

Treatment at that dose was studied in both anti-PD-L1–naive patients with advanced NSCLC, and in NSCLC patients who progressed on anti-PD-L1 treatment, said Dr. Gandhi of New York University Langone Medical Center.

The primary objective of stage 1 was objective response rate, and criteria for advancement were 4 or more responses out of 17 evaluable anti-PD-L1–naive patients (cohort 1), and at least 3 responses out of 31 patients who progressed on anti-PD-L1 therapy (cohort 2).

Both cohorts met the endpoint, with 4 of 17 evaluable cohort 1 patients (24%) achieving a partial response, and 3 of 31 evaluable cohort 2 patients (10%) achieving a partial response.

In cohort 1, two responses were confirmed and two were unconfirmed. One of the unconfirmed patients had malignant pericardial effusion, but remains on study with continued clinical benefit, Dr. Gandhi said, noting that three patients remain on study in all.

“The other notable thing I’d like to point out here … is that the majority of these were patients who did not have high levels of expression of PD-L1,” she said.

In cohort 2 patients, two responses were confirmed and one was unconfirmed. Three patients remain on study.

“In both of these cohorts there are a couple of patients who’ve had quite durable responses,” she said.

The best response to prior anti-PD-1therapy in the cohort 2 patients who had a response was stable disease (two patients). The response to prior therapy was unknown in one patient, she noted.

“All of them had clear regressions, after that initial PD-1 therapy, with this combination,” she said, noting that two had “essentially negative PD-L1 expression, and none had high levels of expression.”

Treatment was associated with grade 3/4 adverse events deemed drug related in 31% of patients; the most common of these events, occurring in at least 10% of patients in cohort 1, were hypophosphatemia and neutropenia, and in cohort 2 were fatigue, anemia, anorexia, and pneumonitis; 13% of patients discontinued treatment due to an adverse event, Dr. Gandhi said.

Of note, there were reductions in circulating myeloid derived suppressor cells in both cohorts following treatment.

Based on the responses seen in this first stage of the study, cohort 2 has advanced to stage 2 and has completed enrollment. Additional patients have not been enrolled in cohort 1, but that is still under consideration, she said.

Dr. Gandhi reported having no disclosures.

sworcester@frontlinemedcom.com

NATIONAL HARBOR, MD. – The oral, class I selective histone deacetylase (HDAC) inhibitor entinostat given in combination with pembrolizumab demonstrated antitumor activity and acceptable safety in patients with non–small cell lung cancer in the phase 1b/2 ENCORE 601 study.

Entinostat, which has been shown in preclinical models to enhance suppressor cells in the tumor microenvironment, was evaluated in ENCORE 601 as a treatment for non–small cell lung cancer (NSCLC), melanoma, and colorectal cancer. Previously reported phase 1 results showed that an oral dose of 5 mg weekly plus 200 mg of pembrolizumab given intravenously every 3 weeks deserved further exploration for these indications, according to Leena Gandhi, MD, who reported phase 2, stage 1 results from the lung cancer arm of the Simon two-stage study at the annual meeting of the Society for Immunotherapy of Cancer.

Treatment at that dose was studied in both anti-PD-L1–naive patients with advanced NSCLC, and in NSCLC patients who progressed on anti-PD-L1 treatment, said Dr. Gandhi of New York University Langone Medical Center.

The primary objective of stage 1 was objective response rate, and criteria for advancement were 4 or more responses out of 17 evaluable anti-PD-L1–naive patients (cohort 1), and at least 3 responses out of 31 patients who progressed on anti-PD-L1 therapy (cohort 2).

Both cohorts met the endpoint, with 4 of 17 evaluable cohort 1 patients (24%) achieving a partial response, and 3 of 31 evaluable cohort 2 patients (10%) achieving a partial response.

In cohort 1, two responses were confirmed and two were unconfirmed. One of the unconfirmed patients had malignant pericardial effusion, but remains on study with continued clinical benefit, Dr. Gandhi said, noting that three patients remain on study in all.

“The other notable thing I’d like to point out here … is that the majority of these were patients who did not have high levels of expression of PD-L1,” she said.

In cohort 2 patients, two responses were confirmed and one was unconfirmed. Three patients remain on study.

“In both of these cohorts there are a couple of patients who’ve had quite durable responses,” she said.

The best response to prior anti-PD-1therapy in the cohort 2 patients who had a response was stable disease (two patients). The response to prior therapy was unknown in one patient, she noted.

“All of them had clear regressions, after that initial PD-1 therapy, with this combination,” she said, noting that two had “essentially negative PD-L1 expression, and none had high levels of expression.”

Treatment was associated with grade 3/4 adverse events deemed drug related in 31% of patients; the most common of these events, occurring in at least 10% of patients in cohort 1, were hypophosphatemia and neutropenia, and in cohort 2 were fatigue, anemia, anorexia, and pneumonitis; 13% of patients discontinued treatment due to an adverse event, Dr. Gandhi said.

Of note, there were reductions in circulating myeloid derived suppressor cells in both cohorts following treatment.

Based on the responses seen in this first stage of the study, cohort 2 has advanced to stage 2 and has completed enrollment. Additional patients have not been enrolled in cohort 1, but that is still under consideration, she said.

Dr. Gandhi reported having no disclosures.

sworcester@frontlinemedcom.com

NATIONAL HARBOR, MD. – The oral, class I selective histone deacetylase (HDAC) inhibitor entinostat given in combination with pembrolizumab demonstrated antitumor activity and acceptable safety in patients with non–small cell lung cancer in the phase 1b/2 ENCORE 601 study.

Entinostat, which has been shown in preclinical models to enhance suppressor cells in the tumor microenvironment, was evaluated in ENCORE 601 as a treatment for non–small cell lung cancer (NSCLC), melanoma, and colorectal cancer. Previously reported phase 1 results showed that an oral dose of 5 mg weekly plus 200 mg of pembrolizumab given intravenously every 3 weeks deserved further exploration for these indications, according to Leena Gandhi, MD, who reported phase 2, stage 1 results from the lung cancer arm of the Simon two-stage study at the annual meeting of the Society for Immunotherapy of Cancer.

Treatment at that dose was studied in both anti-PD-L1–naive patients with advanced NSCLC, and in NSCLC patients who progressed on anti-PD-L1 treatment, said Dr. Gandhi of New York University Langone Medical Center.

The primary objective of stage 1 was objective response rate, and criteria for advancement were 4 or more responses out of 17 evaluable anti-PD-L1–naive patients (cohort 1), and at least 3 responses out of 31 patients who progressed on anti-PD-L1 therapy (cohort 2).

Both cohorts met the endpoint, with 4 of 17 evaluable cohort 1 patients (24%) achieving a partial response, and 3 of 31 evaluable cohort 2 patients (10%) achieving a partial response.

In cohort 1, two responses were confirmed and two were unconfirmed. One of the unconfirmed patients had malignant pericardial effusion, but remains on study with continued clinical benefit, Dr. Gandhi said, noting that three patients remain on study in all.

“The other notable thing I’d like to point out here … is that the majority of these were patients who did not have high levels of expression of PD-L1,” she said.

In cohort 2 patients, two responses were confirmed and one was unconfirmed. Three patients remain on study.

“In both of these cohorts there are a couple of patients who’ve had quite durable responses,” she said.

The best response to prior anti-PD-1therapy in the cohort 2 patients who had a response was stable disease (two patients). The response to prior therapy was unknown in one patient, she noted.

“All of them had clear regressions, after that initial PD-1 therapy, with this combination,” she said, noting that two had “essentially negative PD-L1 expression, and none had high levels of expression.”

Treatment was associated with grade 3/4 adverse events deemed drug related in 31% of patients; the most common of these events, occurring in at least 10% of patients in cohort 1, were hypophosphatemia and neutropenia, and in cohort 2 were fatigue, anemia, anorexia, and pneumonitis; 13% of patients discontinued treatment due to an adverse event, Dr. Gandhi said.

Of note, there were reductions in circulating myeloid derived suppressor cells in both cohorts following treatment.

Based on the responses seen in this first stage of the study, cohort 2 has advanced to stage 2 and has completed enrollment. Additional patients have not been enrolled in cohort 1, but that is still under consideration, she said.

Dr. Gandhi reported having no disclosures.

sworcester@frontlinemedcom.com

Implementing quality initiatives and creating reporting mechanisms for lung cancer patients can lead to better outcomes, including overall survival. While barriers exist – namely the conflicting perspectives of providers, payers, hospitals, and patients – thoracic oncologic surgeons should seize the opportunity to establish robust quality and value metrics for lung cancer programs, said Whitney S. Brandt, MD, and her coauthors in an expert opinion in the Journal of Thoracic and Cardiovascular Surgery (2017;154:1397-403).

Dr. Brandt, a surgeon at Memorial Sloan Kettering Cancer Center in New York, and her coauthors examined the key elements of quality and value initiatives, categorizing them into preoperative, intraoperative, and postoperative components and primarily focusing on early stage lung cancer. The National Institutes of Health/National Cancer Center provided a grant for the authors’ work.

The preoperative evaluation should at least include CT imaging of the tumor and, for smokers, smoking cessation, said Dr. Brandt and her coauthors. All candidates for pulmonary lung resection should have spirometry and diffusion capacity tests; furthermore, both predicted postoperative forced expiratory volume in 1 second and diffusing capacity of the lungs for CO should be calculated. “Patients with a predicted postoperative value less than 40% for either measurement should be considered high risk for lobectomy and should be offered either sublobar resection or nonsurgical therapy,” they recommended.

Dr. Brandt and her colleagues also clarified preoperative management of patients with cardiac disease. Only patients with significant cardiac disease risk factors need to undergo cardiac testing before lung surgery, and patients with stable cardiac disease do not require revascularization beforehand.

For preoperative staging, the most comprehensive clinical guidelines come from the National Comprehensive Cancer Network, they stated. The guidelines recommend that all patients with a small cell lung cancer or stage II to IV non–small cell lung cancer (NSCLC) receive a brain MRI or – if that’s not available – a head CT with contrast to assess for brain metastasis.

Intraoperative quality measures take into account the surgical approach, including cost, resection and margins, and lymph node evaluation. With regard to surgical approach, trials have shown traditional video-assisted surgery (VATS) lobectomy results in shorter hospital stays and thereby lower costs, as well as fewer complications and deaths, than thoracotomy, said Dr. Brandt and her coauthors. But that cost advantage has not yet carried over to robotic-assisted VATS. That said, “robotic-assisted VATS remains a relatively new technology, and with time and increased robotic platform competition, costs will likely decrease.”

Dr. Brandt and her coauthors also noted that clinical trials support resection margins of 2 cm in patients having surgery for NSCLC and that adequate lymph node evaluation is a critical component of a lung cancer quality initiative. “Regardless of whether lymph nodes are sampled or dissected, we believe that systematic acquisition of mediastinal nodal tissue based on nodal station(s) is a useful quality metric, and, therefore, we recommend each program adopt a preferred approach and track adherence,” they said.

As for postoperative quality metrics, the most obvious are morbidity and mortality. “A quality program should track 30-day or in-hospital mortality, as well as 90-day mortality, following lung cancer resection.” Such metrics can serve as “starting points” for quality improvement initiatives. Length of stay has also emerged as an important metric because it is a surrogate of other metrics, such as patient comorbidities, age, and socioeconomic status. “Length-of-stay metrics likely need to be risk-stratified on the basis of these and other variables to be meaningful to a practicing surgeon,” Dr. Brandt and her coauthors said, adding that: “Studying the effectiveness of enhanced recovery after surgery programs in thoracic surgical oncology poses an opportunity for a well-designed trial.”

Two other key quality metrics for lung cancer programs that need further development were pointed out in the paper: hospital readmissions and tracking of adjuvant therapies. “Programmatic oncologic quality metrics to track appropriate and inappropriate referrals for adjuvant therapy and the number of patients who complete such therapy are important,” they said.

Another step programs should take: Participating in a national or regional database, as recommended by the Society of Thoracic Surgeons, and taking advantage of the “clear benefits to benchmarking your program to others.”

Dr. Brandt and her coauthors reported having no financial disclosures. The National Institutes of Health/National Cancer Center provided grant support.
 

Implementing quality initiatives and creating reporting mechanisms for lung cancer patients can lead to better outcomes, including overall survival. While barriers exist – namely the conflicting perspectives of providers, payers, hospitals, and patients – thoracic oncologic surgeons should seize the opportunity to establish robust quality and value metrics for lung cancer programs, said Whitney S. Brandt, MD, and her coauthors in an expert opinion in the Journal of Thoracic and Cardiovascular Surgery (2017;154:1397-403).

Dr. Brandt, a surgeon at Memorial Sloan Kettering Cancer Center in New York, and her coauthors examined the key elements of quality and value initiatives, categorizing them into preoperative, intraoperative, and postoperative components and primarily focusing on early stage lung cancer. The National Institutes of Health/National Cancer Center provided a grant for the authors’ work.

The preoperative evaluation should at least include CT imaging of the tumor and, for smokers, smoking cessation, said Dr. Brandt and her coauthors. All candidates for pulmonary lung resection should have spirometry and diffusion capacity tests; furthermore, both predicted postoperative forced expiratory volume in 1 second and diffusing capacity of the lungs for CO should be calculated. “Patients with a predicted postoperative value less than 40% for either measurement should be considered high risk for lobectomy and should be offered either sublobar resection or nonsurgical therapy,” they recommended.

Dr. Brandt and her colleagues also clarified preoperative management of patients with cardiac disease. Only patients with significant cardiac disease risk factors need to undergo cardiac testing before lung surgery, and patients with stable cardiac disease do not require revascularization beforehand.

For preoperative staging, the most comprehensive clinical guidelines come from the National Comprehensive Cancer Network, they stated. The guidelines recommend that all patients with a small cell lung cancer or stage II to IV non–small cell lung cancer (NSCLC) receive a brain MRI or – if that’s not available – a head CT with contrast to assess for brain metastasis.

Intraoperative quality measures take into account the surgical approach, including cost, resection and margins, and lymph node evaluation. With regard to surgical approach, trials have shown traditional video-assisted surgery (VATS) lobectomy results in shorter hospital stays and thereby lower costs, as well as fewer complications and deaths, than thoracotomy, said Dr. Brandt and her coauthors. But that cost advantage has not yet carried over to robotic-assisted VATS. That said, “robotic-assisted VATS remains a relatively new technology, and with time and increased robotic platform competition, costs will likely decrease.”

Dr. Brandt and her coauthors also noted that clinical trials support resection margins of 2 cm in patients having surgery for NSCLC and that adequate lymph node evaluation is a critical component of a lung cancer quality initiative. “Regardless of whether lymph nodes are sampled or dissected, we believe that systematic acquisition of mediastinal nodal tissue based on nodal station(s) is a useful quality metric, and, therefore, we recommend each program adopt a preferred approach and track adherence,” they said.

As for postoperative quality metrics, the most obvious are morbidity and mortality. “A quality program should track 30-day or in-hospital mortality, as well as 90-day mortality, following lung cancer resection.” Such metrics can serve as “starting points” for quality improvement initiatives. Length of stay has also emerged as an important metric because it is a surrogate of other metrics, such as patient comorbidities, age, and socioeconomic status. “Length-of-stay metrics likely need to be risk-stratified on the basis of these and other variables to be meaningful to a practicing surgeon,” Dr. Brandt and her coauthors said, adding that: “Studying the effectiveness of enhanced recovery after surgery programs in thoracic surgical oncology poses an opportunity for a well-designed trial.”

Two other key quality metrics for lung cancer programs that need further development were pointed out in the paper: hospital readmissions and tracking of adjuvant therapies. “Programmatic oncologic quality metrics to track appropriate and inappropriate referrals for adjuvant therapy and the number of patients who complete such therapy are important,” they said.

Another step programs should take: Participating in a national or regional database, as recommended by the Society of Thoracic Surgeons, and taking advantage of the “clear benefits to benchmarking your program to others.”

Dr. Brandt and her coauthors reported having no financial disclosures. The National Institutes of Health/National Cancer Center provided grant support.
 

Implementing quality initiatives and creating reporting mechanisms for lung cancer patients can lead to better outcomes, including overall survival. While barriers exist – namely the conflicting perspectives of providers, payers, hospitals, and patients – thoracic oncologic surgeons should seize the opportunity to establish robust quality and value metrics for lung cancer programs, said Whitney S. Brandt, MD, and her coauthors in an expert opinion in the Journal of Thoracic and Cardiovascular Surgery (2017;154:1397-403).

Dr. Brandt, a surgeon at Memorial Sloan Kettering Cancer Center in New York, and her coauthors examined the key elements of quality and value initiatives, categorizing them into preoperative, intraoperative, and postoperative components and primarily focusing on early stage lung cancer. The National Institutes of Health/National Cancer Center provided a grant for the authors’ work.

The preoperative evaluation should at least include CT imaging of the tumor and, for smokers, smoking cessation, said Dr. Brandt and her coauthors. All candidates for pulmonary lung resection should have spirometry and diffusion capacity tests; furthermore, both predicted postoperative forced expiratory volume in 1 second and diffusing capacity of the lungs for CO should be calculated. “Patients with a predicted postoperative value less than 40% for either measurement should be considered high risk for lobectomy and should be offered either sublobar resection or nonsurgical therapy,” they recommended.

Dr. Brandt and her colleagues also clarified preoperative management of patients with cardiac disease. Only patients with significant cardiac disease risk factors need to undergo cardiac testing before lung surgery, and patients with stable cardiac disease do not require revascularization beforehand.

For preoperative staging, the most comprehensive clinical guidelines come from the National Comprehensive Cancer Network, they stated. The guidelines recommend that all patients with a small cell lung cancer or stage II to IV non–small cell lung cancer (NSCLC) receive a brain MRI or – if that’s not available – a head CT with contrast to assess for brain metastasis.

Intraoperative quality measures take into account the surgical approach, including cost, resection and margins, and lymph node evaluation. With regard to surgical approach, trials have shown traditional video-assisted surgery (VATS) lobectomy results in shorter hospital stays and thereby lower costs, as well as fewer complications and deaths, than thoracotomy, said Dr. Brandt and her coauthors. But that cost advantage has not yet carried over to robotic-assisted VATS. That said, “robotic-assisted VATS remains a relatively new technology, and with time and increased robotic platform competition, costs will likely decrease.”

Dr. Brandt and her coauthors also noted that clinical trials support resection margins of 2 cm in patients having surgery for NSCLC and that adequate lymph node evaluation is a critical component of a lung cancer quality initiative. “Regardless of whether lymph nodes are sampled or dissected, we believe that systematic acquisition of mediastinal nodal tissue based on nodal station(s) is a useful quality metric, and, therefore, we recommend each program adopt a preferred approach and track adherence,” they said.

As for postoperative quality metrics, the most obvious are morbidity and mortality. “A quality program should track 30-day or in-hospital mortality, as well as 90-day mortality, following lung cancer resection.” Such metrics can serve as “starting points” for quality improvement initiatives. Length of stay has also emerged as an important metric because it is a surrogate of other metrics, such as patient comorbidities, age, and socioeconomic status. “Length-of-stay metrics likely need to be risk-stratified on the basis of these and other variables to be meaningful to a practicing surgeon,” Dr. Brandt and her coauthors said, adding that: “Studying the effectiveness of enhanced recovery after surgery programs in thoracic surgical oncology poses an opportunity for a well-designed trial.”

Two other key quality metrics for lung cancer programs that need further development were pointed out in the paper: hospital readmissions and tracking of adjuvant therapies. “Programmatic oncologic quality metrics to track appropriate and inappropriate referrals for adjuvant therapy and the number of patients who complete such therapy are important,” they said.

Another step programs should take: Participating in a national or regional database, as recommended by the Society of Thoracic Surgeons, and taking advantage of the “clear benefits to benchmarking your program to others.”

Dr. Brandt and her coauthors reported having no financial disclosures. The National Institutes of Health/National Cancer Center provided grant support.
 

SCOTTSDALE, ARIZ. – In a small, single-center study of patients with subdiaphragmatic hemorrhage, resuscitative endovascular balloon occlusion of the aorta (REBOA) improved hemodynamic status and 30-day survival rates, compared with resuscitative thoracotomy (RT).

Although the technique was first developed during the Korean War, REBOA never really caught on, possibly because of limitations in endovascular technology. But recent advances in surgical technique have revitalized interest.

The funding source was not disclosed. Dr. Smith is on the speakers bureau for Prytime Medical and is a consultant for Boehringer Laboratory LLC.

SCOTTSDALE, ARIZ. – In a small, single-center study of patients with subdiaphragmatic hemorrhage, resuscitative endovascular balloon occlusion of the aorta (REBOA) improved hemodynamic status and 30-day survival rates, compared with resuscitative thoracotomy (RT).

Although the technique was first developed during the Korean War, REBOA never really caught on, possibly because of limitations in endovascular technology. But recent advances in surgical technique have revitalized interest.

The funding source was not disclosed. Dr. Smith is on the speakers bureau for Prytime Medical and is a consultant for Boehringer Laboratory LLC.

SCOTTSDALE, ARIZ. – In a small, single-center study of patients with subdiaphragmatic hemorrhage, resuscitative endovascular balloon occlusion of the aorta (REBOA) improved hemodynamic status and 30-day survival rates, compared with resuscitative thoracotomy (RT).

Although the technique was first developed during the Korean War, REBOA never really caught on, possibly because of limitations in endovascular technology. But recent advances in surgical technique have revitalized interest.

The funding source was not disclosed. Dr. Smith is on the speakers bureau for Prytime Medical and is a consultant for Boehringer Laboratory LLC.

The gut microbome may influence responses to immune checkpoint inhibitors, based on results from two studies, and one of the investigators is now gearing up for the next step - evaluating in a clinical trial whether altering the microflora will actually improve responses.

In the first study, investigators carried out a series of experiments using fecal microbiome samples from patients with metastatic melanoma embarking on therapy with a PD-1 (programmed cell death protein 1) inhibitor.

“In melanoma patients, there were differential signals in the gut microbiome of responders versus nonresponders, and I think the clincher was when we transplanted fecal samples from responders to nonresponders in germ-free mice, essentially reconstituting the microbiome and showing that it equally affected the systemic immunity and antitumor immunity when we implanted tumors, as well as response to checkpoint blockade,” lead author Jennifer A. Wargo, MD, MMSc, of the University of Texas MD Anderson Cancer Center in Houston, said in an interview.

Dr. Wargo and her colleagues first collected buccal and fecal microbiome samples from 112 patients with metastatic melanoma before they began therapy with a PD-1 inhibitor. After performing taxonomic profiling on all samples, they found that there was a clustering effect by response status in the gut microbiome, but not the oral microbiome, and because changes in the oral microbiome did not appear to be related to treatment response, they focused on the gut.

When Dr. Wargo and her colleagues studied the posttherapy microbiomes of 43 patients (30 responders and 13 nonresponders) according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1), they found that the responders had a significantly higher degree of alpha diversity, a measure of species diversity within a specific environment, compared with nonresponders (P less than .01). In addition, responders had a relative abundance of Ruminococcaceae, commonly occurring gut microbes that break down complex carbohydrates, the investigators reported (Science. 2017 Nov. 2. doi: 10.1126/science.aan4236).

They found that patients whose microbiomes were diverse in general, and in particular were enriched with Faecalibacterium and Clostridiales species, were more likely to respond to immunotherapy with a PD-1 inhibitor and have a longer duration of progression-free survival. In contrast, patients whose microbiomes were more enriched with Bacteroidales species were more likely to be nonresponders.

To get a better understanding of the mechanisms whereby gut bacteria may influence response to PD-1 inhibitors, they performed metagenomic analysis on samples from 14 responders and 11 nonresponders, and found that responders had micro-organisms predominantly associated with anabolic functions that may support host immunity, whereas nonresponders had microbiomes where catabolic functions were more common.

The investigators next performed immune profiling, and found that both systemic immunity and local immunity in the tumor microenvironment in responders were associated with the aforementioned favorable gut microbiome.

The researchers then transplanted feces from the human donors into germ-free mice and then injected tumor cells into the mice, and found that tumor growth was significantly reduced, and response to PD-1 inhibition was significantly enhanced, in mice who received feces from responders.

“An obvious next step is to run a clinical trial to test the hypothesis that by modulating the microbiome, you can actually enhance responses to therapy,” Dr. Wargo said. Details of the clinical trial are still being worked out, but will likely involve fecal transfers and other mechanisms for modulating the microbiome in hopes of improving responses to PD-1 inhibitors.

“It’s going to be a very biomarker-heavy trial,” she said. “We’re going to look, certainly, for changes in the microbiome, and will also do a lot of profiling in the blood, the tumor, and in the microbiome to see if there are changes that occur by modulating that microbiome. Then of course we’ll look for differences in response rates in patients as well.”
 

Bacteria also affect epithelial cancers

In a separate study, also published in Science, investigators led by Bertrand Routy, MD, of the Gustave Roussy Cancer Institute in Villejuif, France, reported that patients with non–small cell lung cancer and urothelial carcinoma who had previously used systemic antibiotics had reduced survival when treated with a PD-1 inhibitor, compared with patients who had never taken antibiotics (Science. 2017 Nov. 2 doi: 10.1126/science.aan3706).

Analysis of the gut microbiome in these patients showed that higher levels of Akkermansia muciniphila were associated with the best clinical outcomes, with the species detectable in the microbiome of 69% of patients who had partial responses to anti–PD-1 therapy, and in 58% of those with stable disease. In contrast, the bacterium was detectable in only 34% of patients who experienced disease progression.

As in the experiments by Dr. Wargo and her associates, when the French investigators first treated mice with antibiotics and then gave them oral supplements containing the bacteria, the supplements restored response to PD-1 blockade,

“We conclude from the study that the gut microbiome markedly influences the outcome of PD-1 blockade in mice and patients,” Dr. Routy and his associates wrote.

They acknowledged that the mechanism whereby a common organism such as Akkermansia muciniphila might have an immunomodulatory effect is still unknown,

“Irrespective of these remaining questions, our findings suggest that the microbiome governs the cancer-immune set point of cancer-bearing individuals and offer[s] novel avenues for manipulating the gut ecosystem to circumvent primary resistance to [immune checkpoint inhibitors],” they wrote.

The study by Dr. Wargo and her colleagues was supported by contributions to the University of Texas MD Anderson Melanoma Moon Shots program. Dr. Wargo is supported by the Binational Science Foundation, Melanoma Research Alliance, Stand Up to Cancer, and the MDACC Melanoma Moon Shots Program. The work by Dr. Routy and his associates was supported by the Goustave Roussy Cancer Institute and McGill University. Coauthors were supported by the National Cancer Institute of France and other agencies and philanthropies.

The gut microbome may influence responses to immune checkpoint inhibitors, based on results from two studies, and one of the investigators is now gearing up for the next step - evaluating in a clinical trial whether altering the microflora will actually improve responses.

In the first study, investigators carried out a series of experiments using fecal microbiome samples from patients with metastatic melanoma embarking on therapy with a PD-1 (programmed cell death protein 1) inhibitor.

“In melanoma patients, there were differential signals in the gut microbiome of responders versus nonresponders, and I think the clincher was when we transplanted fecal samples from responders to nonresponders in germ-free mice, essentially reconstituting the microbiome and showing that it equally affected the systemic immunity and antitumor immunity when we implanted tumors, as well as response to checkpoint blockade,” lead author Jennifer A. Wargo, MD, MMSc, of the University of Texas MD Anderson Cancer Center in Houston, said in an interview.

Dr. Wargo and her colleagues first collected buccal and fecal microbiome samples from 112 patients with metastatic melanoma before they began therapy with a PD-1 inhibitor. After performing taxonomic profiling on all samples, they found that there was a clustering effect by response status in the gut microbiome, but not the oral microbiome, and because changes in the oral microbiome did not appear to be related to treatment response, they focused on the gut.

When Dr. Wargo and her colleagues studied the posttherapy microbiomes of 43 patients (30 responders and 13 nonresponders) according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1), they found that the responders had a significantly higher degree of alpha diversity, a measure of species diversity within a specific environment, compared with nonresponders (P less than .01). In addition, responders had a relative abundance of Ruminococcaceae, commonly occurring gut microbes that break down complex carbohydrates, the investigators reported (Science. 2017 Nov. 2. doi: 10.1126/science.aan4236).

They found that patients whose microbiomes were diverse in general, and in particular were enriched with Faecalibacterium and Clostridiales species, were more likely to respond to immunotherapy with a PD-1 inhibitor and have a longer duration of progression-free survival. In contrast, patients whose microbiomes were more enriched with Bacteroidales species were more likely to be nonresponders.

To get a better understanding of the mechanisms whereby gut bacteria may influence response to PD-1 inhibitors, they performed metagenomic analysis on samples from 14 responders and 11 nonresponders, and found that responders had micro-organisms predominantly associated with anabolic functions that may support host immunity, whereas nonresponders had microbiomes where catabolic functions were more common.

The investigators next performed immune profiling, and found that both systemic immunity and local immunity in the tumor microenvironment in responders were associated with the aforementioned favorable gut microbiome.

The researchers then transplanted feces from the human donors into germ-free mice and then injected tumor cells into the mice, and found that tumor growth was significantly reduced, and response to PD-1 inhibition was significantly enhanced, in mice who received feces from responders.

“An obvious next step is to run a clinical trial to test the hypothesis that by modulating the microbiome, you can actually enhance responses to therapy,” Dr. Wargo said. Details of the clinical trial are still being worked out, but will likely involve fecal transfers and other mechanisms for modulating the microbiome in hopes of improving responses to PD-1 inhibitors.

“It’s going to be a very biomarker-heavy trial,” she said. “We’re going to look, certainly, for changes in the microbiome, and will also do a lot of profiling in the blood, the tumor, and in the microbiome to see if there are changes that occur by modulating that microbiome. Then of course we’ll look for differences in response rates in patients as well.”
 

Bacteria also affect epithelial cancers

In a separate study, also published in Science, investigators led by Bertrand Routy, MD, of the Gustave Roussy Cancer Institute in Villejuif, France, reported that patients with non–small cell lung cancer and urothelial carcinoma who had previously used systemic antibiotics had reduced survival when treated with a PD-1 inhibitor, compared with patients who had never taken antibiotics (Science. 2017 Nov. 2 doi: 10.1126/science.aan3706).

Analysis of the gut microbiome in these patients showed that higher levels of Akkermansia muciniphila were associated with the best clinical outcomes, with the species detectable in the microbiome of 69% of patients who had partial responses to anti–PD-1 therapy, and in 58% of those with stable disease. In contrast, the bacterium was detectable in only 34% of patients who experienced disease progression.

As in the experiments by Dr. Wargo and her associates, when the French investigators first treated mice with antibiotics and then gave them oral supplements containing the bacteria, the supplements restored response to PD-1 blockade,

“We conclude from the study that the gut microbiome markedly influences the outcome of PD-1 blockade in mice and patients,” Dr. Routy and his associates wrote.

They acknowledged that the mechanism whereby a common organism such as Akkermansia muciniphila might have an immunomodulatory effect is still unknown,

“Irrespective of these remaining questions, our findings suggest that the microbiome governs the cancer-immune set point of cancer-bearing individuals and offer[s] novel avenues for manipulating the gut ecosystem to circumvent primary resistance to [immune checkpoint inhibitors],” they wrote.

The study by Dr. Wargo and her colleagues was supported by contributions to the University of Texas MD Anderson Melanoma Moon Shots program. Dr. Wargo is supported by the Binational Science Foundation, Melanoma Research Alliance, Stand Up to Cancer, and the MDACC Melanoma Moon Shots Program. The work by Dr. Routy and his associates was supported by the Goustave Roussy Cancer Institute and McGill University. Coauthors were supported by the National Cancer Institute of France and other agencies and philanthropies.

The gut microbome may influence responses to immune checkpoint inhibitors, based on results from two studies, and one of the investigators is now gearing up for the next step - evaluating in a clinical trial whether altering the microflora will actually improve responses.

In the first study, investigators carried out a series of experiments using fecal microbiome samples from patients with metastatic melanoma embarking on therapy with a PD-1 (programmed cell death protein 1) inhibitor.

“In melanoma patients, there were differential signals in the gut microbiome of responders versus nonresponders, and I think the clincher was when we transplanted fecal samples from responders to nonresponders in germ-free mice, essentially reconstituting the microbiome and showing that it equally affected the systemic immunity and antitumor immunity when we implanted tumors, as well as response to checkpoint blockade,” lead author Jennifer A. Wargo, MD, MMSc, of the University of Texas MD Anderson Cancer Center in Houston, said in an interview.

Dr. Wargo and her colleagues first collected buccal and fecal microbiome samples from 112 patients with metastatic melanoma before they began therapy with a PD-1 inhibitor. After performing taxonomic profiling on all samples, they found that there was a clustering effect by response status in the gut microbiome, but not the oral microbiome, and because changes in the oral microbiome did not appear to be related to treatment response, they focused on the gut.

When Dr. Wargo and her colleagues studied the posttherapy microbiomes of 43 patients (30 responders and 13 nonresponders) according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1), they found that the responders had a significantly higher degree of alpha diversity, a measure of species diversity within a specific environment, compared with nonresponders (P less than .01). In addition, responders had a relative abundance of Ruminococcaceae, commonly occurring gut microbes that break down complex carbohydrates, the investigators reported (Science. 2017 Nov. 2. doi: 10.1126/science.aan4236).

They found that patients whose microbiomes were diverse in general, and in particular were enriched with Faecalibacterium and Clostridiales species, were more likely to respond to immunotherapy with a PD-1 inhibitor and have a longer duration of progression-free survival. In contrast, patients whose microbiomes were more enriched with Bacteroidales species were more likely to be nonresponders.

To get a better understanding of the mechanisms whereby gut bacteria may influence response to PD-1 inhibitors, they performed metagenomic analysis on samples from 14 responders and 11 nonresponders, and found that responders had micro-organisms predominantly associated with anabolic functions that may support host immunity, whereas nonresponders had microbiomes where catabolic functions were more common.

The investigators next performed immune profiling, and found that both systemic immunity and local immunity in the tumor microenvironment in responders were associated with the aforementioned favorable gut microbiome.

The researchers then transplanted feces from the human donors into germ-free mice and then injected tumor cells into the mice, and found that tumor growth was significantly reduced, and response to PD-1 inhibition was significantly enhanced, in mice who received feces from responders.

“An obvious next step is to run a clinical trial to test the hypothesis that by modulating the microbiome, you can actually enhance responses to therapy,” Dr. Wargo said. Details of the clinical trial are still being worked out, but will likely involve fecal transfers and other mechanisms for modulating the microbiome in hopes of improving responses to PD-1 inhibitors.

“It’s going to be a very biomarker-heavy trial,” she said. “We’re going to look, certainly, for changes in the microbiome, and will also do a lot of profiling in the blood, the tumor, and in the microbiome to see if there are changes that occur by modulating that microbiome. Then of course we’ll look for differences in response rates in patients as well.”
 

Bacteria also affect epithelial cancers

In a separate study, also published in Science, investigators led by Bertrand Routy, MD, of the Gustave Roussy Cancer Institute in Villejuif, France, reported that patients with non–small cell lung cancer and urothelial carcinoma who had previously used systemic antibiotics had reduced survival when treated with a PD-1 inhibitor, compared with patients who had never taken antibiotics (Science. 2017 Nov. 2 doi: 10.1126/science.aan3706).

Analysis of the gut microbiome in these patients showed that higher levels of Akkermansia muciniphila were associated with the best clinical outcomes, with the species detectable in the microbiome of 69% of patients who had partial responses to anti–PD-1 therapy, and in 58% of those with stable disease. In contrast, the bacterium was detectable in only 34% of patients who experienced disease progression.

As in the experiments by Dr. Wargo and her associates, when the French investigators first treated mice with antibiotics and then gave them oral supplements containing the bacteria, the supplements restored response to PD-1 blockade,

“We conclude from the study that the gut microbiome markedly influences the outcome of PD-1 blockade in mice and patients,” Dr. Routy and his associates wrote.

They acknowledged that the mechanism whereby a common organism such as Akkermansia muciniphila might have an immunomodulatory effect is still unknown,

“Irrespective of these remaining questions, our findings suggest that the microbiome governs the cancer-immune set point of cancer-bearing individuals and offer[s] novel avenues for manipulating the gut ecosystem to circumvent primary resistance to [immune checkpoint inhibitors],” they wrote.

The study by Dr. Wargo and her colleagues was supported by contributions to the University of Texas MD Anderson Melanoma Moon Shots program. Dr. Wargo is supported by the Binational Science Foundation, Melanoma Research Alliance, Stand Up to Cancer, and the MDACC Melanoma Moon Shots Program. The work by Dr. Routy and his associates was supported by the Goustave Roussy Cancer Institute and McGill University. Coauthors were supported by the National Cancer Institute of France and other agencies and philanthropies.

TORONTO – A proposed change to CHEST’s lung cancer screening guideline calls for raising the upper age for screening recent cigarette smokers to 77 years of age from 74 years of age.

This proposal is part of draft guideline that was unveiled during the CHEST annual meeting but is still subject to tweaking by peer review until formal release in early 2018. The draft also offers expanded guidance on how to implement screening, containing three times as many recommendations as the current lung cancer screening guidelines (Chest. 2013 May; 143[5 Suppl]:e78S-e92S).

“We want screening to expand in a safe and effective way,” said Peter J. Mazzone, MD, chair of the expert panel that is preparing the revision for CHEST and a pulmonologist at the Cleveland Clinic. “We are less restrictive with these guidelines” than in the 2013 version.

Dr. Mazzone cited two major changes that will produce modest broadening of the criteria that determine which patients can appropriately get screening. The clearest change was the age range, which expanded from 55-74 years of age set in 2013 to reflect the age criterion for enrollment in the National Lung Screening Trial (New Engl J Med. 2011 Aug 4; 365[5]:395-409). The panel raised the upper age limit to 77 years of age to coincide with what Medicare covers, Dr. Mazzone explained, though it remains short of the 80-year old ceiling recommended by the U.S. Preventive Services Task Force.

The second, subtler change eased back on the outright ban that the 2013 guidelines placed on screening anyone who falls outside the target age range and smoking history (at least 30 pack years and either being a current smoker or having recently quit within the past 15 years) and who is without severe comorbidities.

The guidelines from 2013 said that screening people who fell outside these limits “should not be performed.” In contrast, the new draft guideline simply said that people who fall outside of the age and smoking-history criteria but who are still considered high risk for lung cancer based on a risk-prediction calculator should not “routinely” undergo screening. Additionally, exceptions could be made for certain patients whose high risk appears to warrant screening, Dr. Mazzone and others from the expert panel noted.

The revision specified that a high-risk person outside of the core criteria might still be a reasonable candidate for screening if this person tallies at least a 1.51% risk of developing lung cancer during the next 6 years according to the PLCO_M2012 risk calculator (New Engl J Med. 2013 Feb 21; 368[8]:728-36).

“Some of the evidence allowed us to be a little more flexible,” though not to the point of “opening screening widely” to people who fall outside the core target population; rather, clinicians get to have a little more discretion, said Dr. Mazzone, who directs the Cleveland Clinic’s Lung Cancer Program. “We hope this will lead to more patients being screened in a high quality way,” he said in an interview. The panel strove to “look beyond the National Lung Screening Trial and find other groups of patients who could benefit” from screening. “We say that other high-risk people should not, on the whole, be screened” but that clinicians could consider individuals as appropriate for screening on a case-by-case basis.

The revision “fills in the outline” for screening that was established in the 2013 guidelines, said Gerard A. Silvestri, MD, a member of the revision panel, in a video interview. The updated guideline better detailed who benefits the most from screening and who benefits less, as well as the potential complications screening may cause, said Dr. Silvestri, a professor of medicine and lung cancer pulmonologist at the Medical University of South Carolina in Charleston.

“The sweet spot for screening is patients with a medium lung cancer risk without many comorbidities. We are trying to come up with individualized risk profiling,” explained Dr. Silvestri during the CHEST session. He noted that, in the screening program he runs in Charleston, every person who contacts the program and is interested in screening undergoes risk profiling. Are there people with a risk profile that justifies screening but fall outside the proposed criteria? “Absolutely,” Dr. Silvestri said.

People considering screening also need to recognize its potential harms, noted Renda Soylemez Wiener, MD, another member of the expert panel who spoke at the meeting. She cited five potential harms: death or complications from a biopsy of a screen-detected nodule, surgery for a screen-detected lesion that turns out to be benign, the psychosocial impact of finding a lung nodule, over diagnosis, and the cumulative radiation exposure from serial low-dose chest CT scans. “All of these dangers are real and may be magnified or mitigated as low-dose CT screening is implemented in real world practice,” said Dr. Wiener, a pulmonologist at Boston University.

In addition to four evidence-based recommendations that help define who is and isn’t an appropriate screening candidate, the revised guideline also included 11 mostly consensus-based “suggestions” about how screening programs should ideally operate. These covered issues such as identifying symptomatic patients who require diagnosis rather than screening, having strategies to encourage compliance with annual screening, including smoking cessation treatments in screening programs, and having strategies that minimize overtreatment of potentially indolent cancers.

The goal of these suggestions is to help in the design of high-quality screening programs, said Dr. Mazzone. “It’s not just who you screen but also how you screen.”

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

TORONTO – A proposed change to CHEST’s lung cancer screening guideline calls for raising the upper age for screening recent cigarette smokers to 77 years of age from 74 years of age.

This proposal is part of draft guideline that was unveiled during the CHEST annual meeting but is still subject to tweaking by peer review until formal release in early 2018. The draft also offers expanded guidance on how to implement screening, containing three times as many recommendations as the current lung cancer screening guidelines (Chest. 2013 May; 143[5 Suppl]:e78S-e92S).

“We want screening to expand in a safe and effective way,” said Peter J. Mazzone, MD, chair of the expert panel that is preparing the revision for CHEST and a pulmonologist at the Cleveland Clinic. “We are less restrictive with these guidelines” than in the 2013 version.

Dr. Mazzone cited two major changes that will produce modest broadening of the criteria that determine which patients can appropriately get screening. The clearest change was the age range, which expanded from 55-74 years of age set in 2013 to reflect the age criterion for enrollment in the National Lung Screening Trial (New Engl J Med. 2011 Aug 4; 365[5]:395-409). The panel raised the upper age limit to 77 years of age to coincide with what Medicare covers, Dr. Mazzone explained, though it remains short of the 80-year old ceiling recommended by the U.S. Preventive Services Task Force.

The second, subtler change eased back on the outright ban that the 2013 guidelines placed on screening anyone who falls outside the target age range and smoking history (at least 30 pack years and either being a current smoker or having recently quit within the past 15 years) and who is without severe comorbidities.

The guidelines from 2013 said that screening people who fell outside these limits “should not be performed.” In contrast, the new draft guideline simply said that people who fall outside of the age and smoking-history criteria but who are still considered high risk for lung cancer based on a risk-prediction calculator should not “routinely” undergo screening. Additionally, exceptions could be made for certain patients whose high risk appears to warrant screening, Dr. Mazzone and others from the expert panel noted.

The revision specified that a high-risk person outside of the core criteria might still be a reasonable candidate for screening if this person tallies at least a 1.51% risk of developing lung cancer during the next 6 years according to the PLCO_M2012 risk calculator (New Engl J Med. 2013 Feb 21; 368[8]:728-36).

“Some of the evidence allowed us to be a little more flexible,” though not to the point of “opening screening widely” to people who fall outside the core target population; rather, clinicians get to have a little more discretion, said Dr. Mazzone, who directs the Cleveland Clinic’s Lung Cancer Program. “We hope this will lead to more patients being screened in a high quality way,” he said in an interview. The panel strove to “look beyond the National Lung Screening Trial and find other groups of patients who could benefit” from screening. “We say that other high-risk people should not, on the whole, be screened” but that clinicians could consider individuals as appropriate for screening on a case-by-case basis.

The revision “fills in the outline” for screening that was established in the 2013 guidelines, said Gerard A. Silvestri, MD, a member of the revision panel, in a video interview. The updated guideline better detailed who benefits the most from screening and who benefits less, as well as the potential complications screening may cause, said Dr. Silvestri, a professor of medicine and lung cancer pulmonologist at the Medical University of South Carolina in Charleston.

“The sweet spot for screening is patients with a medium lung cancer risk without many comorbidities. We are trying to come up with individualized risk profiling,” explained Dr. Silvestri during the CHEST session. He noted that, in the screening program he runs in Charleston, every person who contacts the program and is interested in screening undergoes risk profiling. Are there people with a risk profile that justifies screening but fall outside the proposed criteria? “Absolutely,” Dr. Silvestri said.

People considering screening also need to recognize its potential harms, noted Renda Soylemez Wiener, MD, another member of the expert panel who spoke at the meeting. She cited five potential harms: death or complications from a biopsy of a screen-detected nodule, surgery for a screen-detected lesion that turns out to be benign, the psychosocial impact of finding a lung nodule, over diagnosis, and the cumulative radiation exposure from serial low-dose chest CT scans. “All of these dangers are real and may be magnified or mitigated as low-dose CT screening is implemented in real world practice,” said Dr. Wiener, a pulmonologist at Boston University.

In addition to four evidence-based recommendations that help define who is and isn’t an appropriate screening candidate, the revised guideline also included 11 mostly consensus-based “suggestions” about how screening programs should ideally operate. These covered issues such as identifying symptomatic patients who require diagnosis rather than screening, having strategies to encourage compliance with annual screening, including smoking cessation treatments in screening programs, and having strategies that minimize overtreatment of potentially indolent cancers.

The goal of these suggestions is to help in the design of high-quality screening programs, said Dr. Mazzone. “It’s not just who you screen but also how you screen.”

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

TORONTO – A proposed change to CHEST’s lung cancer screening guideline calls for raising the upper age for screening recent cigarette smokers to 77 years of age from 74 years of age.

This proposal is part of draft guideline that was unveiled during the CHEST annual meeting but is still subject to tweaking by peer review until formal release in early 2018. The draft also offers expanded guidance on how to implement screening, containing three times as many recommendations as the current lung cancer screening guidelines (Chest. 2013 May; 143[5 Suppl]:e78S-e92S).

“We want screening to expand in a safe and effective way,” said Peter J. Mazzone, MD, chair of the expert panel that is preparing the revision for CHEST and a pulmonologist at the Cleveland Clinic. “We are less restrictive with these guidelines” than in the 2013 version.

Dr. Mazzone cited two major changes that will produce modest broadening of the criteria that determine which patients can appropriately get screening. The clearest change was the age range, which expanded from 55-74 years of age set in 2013 to reflect the age criterion for enrollment in the National Lung Screening Trial (New Engl J Med. 2011 Aug 4; 365[5]:395-409). The panel raised the upper age limit to 77 years of age to coincide with what Medicare covers, Dr. Mazzone explained, though it remains short of the 80-year old ceiling recommended by the U.S. Preventive Services Task Force.

The second, subtler change eased back on the outright ban that the 2013 guidelines placed on screening anyone who falls outside the target age range and smoking history (at least 30 pack years and either being a current smoker or having recently quit within the past 15 years) and who is without severe comorbidities.

The guidelines from 2013 said that screening people who fell outside these limits “should not be performed.” In contrast, the new draft guideline simply said that people who fall outside of the age and smoking-history criteria but who are still considered high risk for lung cancer based on a risk-prediction calculator should not “routinely” undergo screening. Additionally, exceptions could be made for certain patients whose high risk appears to warrant screening, Dr. Mazzone and others from the expert panel noted.

The revision specified that a high-risk person outside of the core criteria might still be a reasonable candidate for screening if this person tallies at least a 1.51% risk of developing lung cancer during the next 6 years according to the PLCO_M2012 risk calculator (New Engl J Med. 2013 Feb 21; 368[8]:728-36).

“Some of the evidence allowed us to be a little more flexible,” though not to the point of “opening screening widely” to people who fall outside the core target population; rather, clinicians get to have a little more discretion, said Dr. Mazzone, who directs the Cleveland Clinic’s Lung Cancer Program. “We hope this will lead to more patients being screened in a high quality way,” he said in an interview. The panel strove to “look beyond the National Lung Screening Trial and find other groups of patients who could benefit” from screening. “We say that other high-risk people should not, on the whole, be screened” but that clinicians could consider individuals as appropriate for screening on a case-by-case basis.

The revision “fills in the outline” for screening that was established in the 2013 guidelines, said Gerard A. Silvestri, MD, a member of the revision panel, in a video interview. The updated guideline better detailed who benefits the most from screening and who benefits less, as well as the potential complications screening may cause, said Dr. Silvestri, a professor of medicine and lung cancer pulmonologist at the Medical University of South Carolina in Charleston.

“The sweet spot for screening is patients with a medium lung cancer risk without many comorbidities. We are trying to come up with individualized risk profiling,” explained Dr. Silvestri during the CHEST session. He noted that, in the screening program he runs in Charleston, every person who contacts the program and is interested in screening undergoes risk profiling. Are there people with a risk profile that justifies screening but fall outside the proposed criteria? “Absolutely,” Dr. Silvestri said.

People considering screening also need to recognize its potential harms, noted Renda Soylemez Wiener, MD, another member of the expert panel who spoke at the meeting. She cited five potential harms: death or complications from a biopsy of a screen-detected nodule, surgery for a screen-detected lesion that turns out to be benign, the psychosocial impact of finding a lung nodule, over diagnosis, and the cumulative radiation exposure from serial low-dose chest CT scans. “All of these dangers are real and may be magnified or mitigated as low-dose CT screening is implemented in real world practice,” said Dr. Wiener, a pulmonologist at Boston University.

In addition to four evidence-based recommendations that help define who is and isn’t an appropriate screening candidate, the revised guideline also included 11 mostly consensus-based “suggestions” about how screening programs should ideally operate. These covered issues such as identifying symptomatic patients who require diagnosis rather than screening, having strategies to encourage compliance with annual screening, including smoking cessation treatments in screening programs, and having strategies that minimize overtreatment of potentially indolent cancers.

The goal of these suggestions is to help in the design of high-quality screening programs, said Dr. Mazzone. “It’s not just who you screen but also how you screen.”

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler