Discussant of the POSEIDON trial, Julie Brahmer, MD, MSc, FASCO, Co-Director of the Upper Aerodigestive Department within the Bloomberg~Kimmel Institute for Cancer Immunotherapy at Johns Hopkins Medicine, applauded the numerous treatment choices now available to patients with metastatic non–small cell lung cancer (NSCLC) while encouraging the use of PD-L1 status to help determine which combination to administer.

Julie Brahmer, MD, MSc, FASCO

“In PD-L1–high disease across histologies, single-agent PD-1 or PD-L1 is still appropriate for use,” Dr. Brahmer explained. “I don’t think CTLA-4 plus PD-L1 plus chemotherapy gives any advantage, but I would like to see the tail of the curve to determine whether there’s any advantage in this patient population.”

For patients with PD-L1–negative disease, however, Dr. Brahmer reported that CTLA-4 antibodies “seem to provide a benefit.”

“In the CheckMate studies, in patients with squamous cell histology, the addition of CTLA-4 antibodies demonstrated an advantage over a single-agent immuno-oncology plus chemotherapy,” commented Dr. Brahmer. She noted that the POSEIDON study has not yet been analyzed by histology and PD-L1 status.

Key Questions Remain

According to Dr. Brahmer, although the results of the POSEIDON study showed that combining PD-L1 and CTLA-4 antibodies improves progression-free survival, key questions remain.

Dr. Brahmer asked: “What does CTLA-4 add to the PD-1 blockade? Is the slightly increased toxicity worth a slightly increased long-term duration of response, improved progression-free survival, and overall survival? We need to determine which patient populations truly need CTLA-4 immune checkpoint blockade by finding a biomarker for CTLA-4 benefit.” 

DISCLOSURE: Dr. Brahmer has received honoraria from Roche/Genentech; has served as a consultant or advisor to Amgen, Bristol Myers Squibb, Celgene, Genentech, Janssen Oncology, Lilly, Merck, and Syndax; has received research funding from Revolution; has received institutional research funding from AstraZeneca, Bristol Myers Squibb, Incyte, and Spectrum; has been reimbursed for travel, accommodations, or other expenses by Bristol Myers Squibb and Roche/Genentech; and has held other relationships with Bristol Myers Squibb, Janssen Oncology, and Merck.