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

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 EGFR or ALK 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 KRAS, TP53, or STK11 mutational status.

Despite this, the results showed that patients harboring STK11 mutations had worse prognosis compared with patients with STK11 wild-type NSCLC, which was in-line with expectations based on observations from past studies, Ramalingam explains.

Although the number of patients with KEAP1 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 KRAS, TP53, or STK11 mutation status, Ramalingam concludes.