Study discussant Taofeek Kunie Owonikoko, MD, PhD, Professor and Vice Chair of Hematology/Oncology, Winship Cancer Institute at Emory University, Atlanta, had praise for the design of KEYNOTE-604. He noted the adoption of the combination of pembrolizumab plus etoposide/platinum for the treatment of extensive-stage small cell lung cancer (SCLC) would depend on regulatory approval.

KEYNOTE-604 and other clinical trials presented at the same session showed the addition of immune checkpoint inhibitor to chemotherapy for SCLC yielded “a reproducible pattern of efficacy improvement, including a 24% reduction in the risk of death and a 24% reduction in the risk of disease progression,” noted Dr. Owonikoko. “Additionally, the trials showed a modest impact on overall survival and a consistent improvement in overall survival pattern at 12 months of about 50% and about 22% at 24 months.” These results are far better than those reported in a Cochrane analysis of treatment outcomes prior to the introduction of immune checkpoint inhibitors for SCLC: 12-month overall survival of 29.37% and 24-month overall survival of 6.93%.¹

To date, studies suggest the concurrent use of immune checkpoint inhibitor and chemotherapy is “important,” but Dr. Owonikoko disagrees that immunotherapy should be reserved for maintenance therapy. “I would caution against this [ie, used as maintenance therapy alone], because these trials were not designed to answer that question,” he stated.

Impact on Clinical Practice

Turning to KEYNOTE-604, Dr. Owonikoko said pembrolizumab added to chemotherapy achieved a positive impact on progression-free survival and a trend toward improved overall survival. “However, the study did not meet the high-pressured predefined threshold for success in terms of the P value for overall survival,” he admitted.

Dr. Owonikoko continued: “The immediate impact of this trial on practice is limited at present, and the future impact is absent without any supportive regulatory decision. Nonetheless, pembrolizumab plus chemotherapy remains a viable platform for the development of novel treatment strategies for the future. The study highlights the value of an uncomplicated study design and an analytic plan to ensure accurate results.”

Moving Forward

According to Dr. Owonikoko, the future of immune checkpoint inhibitors in SCLC will be influenced by identifying biomarkers. Thus far, PD-L1 expression and tumor mutational burden have not paid off in that regard. New approaches are being explored, and “attempts to define biomarkers will be key going forward,” he added.

“The approved regimens for newly diagnosed extensive-stage SCLC include combinations of the immune checkpoint inhibitors durvalumab and atezolizumab, each with a platinum doublet. “The data on pembrolizumab … are compelling to make this regimen an acceptable platform for developing new treatment strategies,” concluded Dr. Owonikoko. 

DISCLOSURE: Dr. Owonikoko owns stock in Cambium Oncology; has served as a consultant or advisor to AbbVie, Amgen, Armo BioSciences, AstraZeneca, Bayer, BerGenBio, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eisai, EMD Serono, G1 Therapeutics, Lilly, MedImmune, Merck, Novartis, PharmaMar, Sandoz, Seattle Genetics, Takeda, and Xcovery; and has received institutional research funding from AbbVie Aeglea BioTherapeutics, Amgen, Astellas Pharma, AstraZeneca/MedImmune, Bayer, Bristol-Myers Squibb, Celgene, Corvus Pharmaceuticals, Fujifilm, G1 Therapeutics, Incyte, Loxo/Lilly, Merck, Novartis, Pfizer, Regeneron, Stem CentRx, and United Therapeutics.

REFERENCE

1. Amarasena IU, Chatterjee S, Walters JAE, et al: Platinum versus non-platinum chemotherapy regimens for small cell lung cancer. Cochrane Database Syst Rev (8):CD006849, 2015.