Dr. Garon on the Current Landscape of PD-L1 and CTLA-4 Inhibitor Regimens in NSCLC

Edward B. Garon, MD, MS, professor of medicine, Department of Medicine, Division of Hematology/Oncology, David Geffen School of Medicine, the University of California, Los Angeles (UCLA), UCLA Health, discusses the use of PD-L1 inhibitor and CTLA-4 inhibitor combinations in non–small cell lung cancer (NSCLC).

There are currently 2 first-line PD-L1 and CTLA-4 inhibitor combinations approved by the FDA for use in NSCLC, Garon begins.

The combination of nivolumab (Opdivo) and ipilimumab (Yervoy) plus 2 cycles of platinum-based chemotherapy gained approval in May 2020 for patients with metastatic and recurrent NSCLC without EGFR or ALK alterations, Garon says. The combination of nivolumab and ipilimumab was first approved for patients with PD-L1 positivity based on findings from the phase 3 CheckMate-227 trial (NCT02477826). Shortly after, the triplet was approved for use in patients regardless of PD-L1 expression based on findings from the phase 3 CheckMate-9LA trial (NCT03215706).

Data from the phase 3 POSEIDON study (NCT03164616) led to the FDA approval of durvalumab (Imfinzi) and tremelimumab (Imjudo) plus chemotherapy in this same population on November 10, 2022, Garon continues. Patients in this trial were randomized to either 4 cycles of tremelimumab, durvalumab, and platinum-based chemotherapy followed by durvalumab and maintenance chemotherapy every 4 weeks and a fifth tremelimumab dose at week 16; 4 cycles of durvalumab plus chemotherapy followed by durvalumab and maintenance chemotherapy; or 6 cycles of chemotherapy followed by maintenance chemotherapy.

Patients in the POSEIDON trial received a greater number of chemotherapy cycles than patients in CheckMate-9LA, who received only 2 cycles in the experimental arm, Garon notes. However, patients in the CheckMate-227 and CheckMate-9LA trials continued ipilimumab treatment compared with patients in POSIDEON who received only 1 cycle of post-chemotherapy tremelimumab, Garon qualifies.

These variations in the treatment schedule for these regimens produce different toxicity profiles, Garon continues. For example, the CheckMate-9LA approach allows for earlier chemotherapy cessation, reducing chemotherapy-related toxicities, he explains. Conversely, the POSEIDON regimen incorporates an earlier cessation of tremelimumab, Garon says. As CTLA-4 inhibitors are known to produce significant immune-related toxicities, this approach could also reduce adverse effects, Garon concludes.

Editor’s Note: Dr. Garon has reported consulting or advisory roles with Abbvie, ABL-Bio, AstraZeneca, Boehringer-Ingelheim, Bristol Myers Squibb, Dracen Pharmaceuticals, EMD Serono, Eisai, Eli Lilly, Gilead, GlaxoSmithKline, Ipsen, Merck, Natera, Novartis, Personalis, Regeneron, Sanofi, Shionogi, and Xilio; and has received grant/research support from ABL-Bio, AstraZeneca, Bristol Myers Squibb, Dynavax Technologies, Eli Lilly, EMD Serono, Genentech, Iovance Biotherapeutics, Merck, Mirati Therapeutics, Neon Therapeutics, and Novartis.