Formal discussant of the CheckMate 816 trial, Jhanelle E. Gray, MD, of Moffitt Cancer Center, Tampa, said that both neoadjuvant and adjuvant therapies have been shown to improve overall survival and relapse-free survival in non–small cell lung cancer (NSCLC).

“Overall, neoadjuvant outcomes compare with adjuvant outcomes. The aim is to eliminate micrometastatic disease. The question is how to choose among these options. In the real world, adjuvant chemotherapy is more commonly used for patients with stage II and III NSCLC,” she told listeners.

“The study met its primary endpoint in an intent-to-treat analysis, with a pathologic complete response rate of 24% in the nivolumab arm vs 2.2% in the chemotherapy arm,” stated Dr. Gray. However, she questioned the validity of pathologic complete response as a surrogate endpoint for survival in patients treated with immunotherapy.

“There is a clear association with pathologic complete response and survival with neoadjuvant chemotherapy, but more study is needed to validate these findings in immunotherapy,” Dr. Gray said.

Jhanelle E. Gray, MD

Moving Forward

“The event-free survival and overall survival results of CheckMate 816 will be important and are pending longer follow-up. For trials with major pathologic response as a primary endpoint, we must consider many factors that include trial design and training of pathologists,” she noted.

Various ongoing studies are looking at the combination of immunotherapy and chemotherapy as neoadjuvant treatment and as adjuvant treatment in NSCLC. “We will want to see the full result of these trials,” Dr. Gray said.

Depending on the results of ongoing trials, “in the future, treatment algorithms for neoadjuvant chemotherapy may not only apply to stage IV NSCLC, but also to earlier-stage lung cancer,” she added.

DISCLOSURE: Dr. Gray has served as a consultant or advisor to AstraZeneca, Axiom Healthcare Strategies, Blueprint Medicines, Bristol Myers Squibb, EMD Serono, Inivata, Janssen Scientific Affairs, Lilly, Merck Sharp & Dohme, Novartis, and Sanofi; has received institutional research funding from Array BioPharma, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, G1 Therapeutics, Genentech/Roche, Ludwig Institute for Cancer Research, Merck, Novartis, and Pfizer; and has been reimbursed for travel, accommodations, or other expenses by Bristol Myers Squibb, EMD Serono, Inivata, Merck, Merck Sharp & Dohme, and Novartis.