Suresh S. Ramalingam, MD, FACP, FASCO, professor, Department of Hematology and Medical Oncology, Roberto C. Goizueta Distinguished Chair for Cancer Research, Emory University School of Medicine, executive director, Winship Cancer Institute of Emory University, associate vice president for cancer, Woodruff Health Sciences Center, discusses the results of an exploratory analysis of the ongoing phase 3 CheckMate 227 trial (NCT02477826) in advanced non–small cell lung cancer (NSCLC).

In part 1 of the CheckMate 227 trial, patients with PD-L1–positive stage IV or recurrent NSCLC derived durable and long-term clinical benefit with nivolumab (Opdivo) plus ipilimumab (Yervoy) compared with chemotherapy. Based on these results, in May 2020, the FDA approved the combination for the first-line treatment of patients with metastatic NSCLC not harboring an 

 genomic tumor aberration and PD-L1 expression of 1% or greater. 

During the 2021 ESMO Immuno-Oncology Congress, findings from an exploratory analysis of the CheckMate 227 study were presented. The results showed that patients derived benefit with frontline nivolumab/ipilimumab vs chemotherapy irrespective of 

Despite this, the results showed that patients harboring 

 mutations had worse prognosis compared with patients with 

 wild-type NSCLC, which was in-line with expectations based on observations from past studies, Ramalingam explains. 

 mutations was limited, the 4-year overall survival (OS) rate was 44% with nivolumab/ipilimumab compared with 0% with chemotherapy, but definitive conclusions cannot yet be drawn, Ramalingam says. 

Progression-free survival was consistent with the OS findings, suggesting that the analysis supports nivolumab/ipilimumab vs chemotherapy for patients with advanced NSCLC regardless of 

Videos

Suresh S. Ramalingam, MD, FACP, FASCO, discusses the results of an exploratory analysis of the ongoing phase 3 CheckMate 227 trial in advanced non–small cell lung cancer. 



Dr. Ramalingam on the Results of an Exploratory Analysis of the CheckMate 227 Trial in NSCLC 

Suresh S. Ramalingam, MD, FASCO, deputy director, ​director, Lung Cancer Program, Winship Cancer Institute of Emory University, Roberto C. Goizueta Distinguished Chair for Cancer Research, professor, assistant dean for cancer research, director, Division of Medical Oncology, Department of Hematology and Medical Oncology, Emory University School of Medicine, discusses limitations with immunotherapy in non–small cell lung cancer (NSCLC).

Over the past few years, significant progress has been made with immunotherapy and targeted therapy in NSCLC, Ramalingam says. As a result, patients are now experiencing prolonged survival and improved quality of life.

However, only a small subset of patients will respond to immunotherapy, ​explains Ramalingam. As such, ​utilizing PD-L1 as a biomarker can help to predict which patients will benefit from immunotherapy. 

Ultimately, improv​ing the percentage of patients that benefit from checkpoint inhibitors remains an unmet need in NSCLC, ​says Ramalingam.

Additionally, developing novel therapies for patients who become resistant to checkpoint inhibitors should be a focus of future research efforts, Ramalingam concludes.

Suresh S. Ramalingam, MD, FASCO, discusses limitations with immunotherapy in non–small cell lung cancer. 

Dr. Ramalingam on Limitations With Immunotherapy in NSCLC

Suresh S. Ramalingam, MD, FASCO, deputy director, ​director, Lung Cancer Program, Winship Cancer Institute of Emory University, Roberto C. Goizueta Distinguished Chair for Cancer Research, professor, assistant dean for cancer research, director, Division of Medical Oncology, Department of Hematology and Medical Oncology, Emory University School of Medicine, discusses the utility of nivolumab (Opdivo) plus ipilimumab (Yervoy) in metastatic or recurrent non–small cell lung cancer (NSCLC).

In May 2020, the FDA approved the combination of nivolumab (Opdivo) plus ipilimumab (Yervoy) for the frontline treatment of patients with PD-L1–positive metastatic NSCLC based on findings from the phase 3 CheckMate-227 trial. This provides patients with a chemotherapy-free option that has the ability to prolong survival, says Ramalingam.

The next step is to evaluate the combination in other settings of NSCLC, such as in the stage III setting wherein patients receive concurrent chemoradiation followed by consolidative immunotherapy, explains Ramalingam.

Additionally, this ​regimen may serve as a backbone for other novel agents to build upon, Ramalingam concludes.

Suresh S. Ramalingam, MD, FASCO, discusses the utility of nivolumab plus ipilimumab in metastatic or recurrent non–small cell lung cancer.

Dr. Ramalingam on Next Steps With Nivolumab/Ipilimumab in NSCLC

Suresh A. Ramalingam, MD, deputy director of Winship Cancer Institute of Emory University, discusses data with pembrolizumab (Keytruda) and chemotherapy in patients with non—small cell lung cancer (NSCLC).

Cohort G of the KEYNOTE-21 trial, which was a randomized phase II study, showed that adding pembrolizumab to chemotherapy in patients with nonsquamous disease was associated with an improved progression-free survival, high response rates, and a trend toward improved survival. That appears to be confirmed by the KEYNOTE-189 study, explains Ramalingam.

This brings the combination approach of chemotherapy plus immunotherapy to the forefront. Physicians no longer look at all patients with nonsquamous lung cancer as one group in the context of immunotherapy. Ramalingam believes it is important to think about patients who have a high PD-L1 expression of 50%.

Positive data with patients with PD-L1 expression greater than 50% has suggested that pembrolizumab monotherapy is superior to chemotherapy alone, as it has demonstrated a median overall survival of approximately 30 months. Whether chemotherapy plus pembrolizumab is going to be better than pembrolizumab alone is still unknown, says Ramalingam.

Suresh A. Ramalingam, MD, deputy director of Winship Cancer Institute of Emory University, discusses data with pembrolizumab (Keytruda) and chemotherapy in patients with non–small cell lung cancer (NSCLC).

Suresh A. Ramalingam, MD

Articles

Dr. Ramalingam on the Results of an Exploratory Analysis of the CheckMate 227 Trial in NSCLC

Dr. Ramalingam on Limitations With Immunotherapy in NSCLC

Dr. Ramalingam on Next Steps With Nivolumab/Ipilimumab in NSCLC

Dr. Ramalingam on Pembrolizumab and Chemotherapy in NSCLC