Small cell lung cancer: a slightly less orphan disease after immunotherapy.

Small cell lung cancer (SCLC) is an aggressive malignancy accounting for 15% of all diagnosed cases of lung cancer. After >15 years without any clinically relevant therapeutic advances, extensive-disease SCLC has become the second thoracic malignancy for which immune checkpoint inhibitors (ICIs) have shifted the treatment paradigm to improve overall survival. Today, atezolizumab or durvalumab in combination with platinum-etoposide chemotherapy is considered the new standard of care in the first-line setting in SCLC. However, the magnitude of benefit with this immune-chemotherapy strategy in SCLC is more modest than that observed in metastatic non-small-cell lung cancer patients. The immunosuppressive phenotype of SCLC plays an important role in hampering ICI efficacy and may explain the differences in outcomes between these two types of lung cancer. In this review, we provide a summary of recent therapeutic advances in SCLC in light of ICIs, as well as current challenges of this strategy in patients who are elderly, have poor performance status or brain metastases. We also address future perspectives of immunotherapeutic strategies currently in clinical development for these patients.
Competing Interests: Disclosure RM reports personal fees and other from MSD and OSE Immunotherapeutics, other from Boehringer Ingelheim, Pfizer, BMS, AstraZeneca and Roche, outside the submitted work. BB reports grants from AbbVie, Amgen, AstraZeneca, Biogen, Blueprint Medicines, BMS, Celgene, Eli Lilly, GSK, Ignyta, IPSEN, Merck KGaA, MSD, Nektar, Onxeo, Pfizer, PharmaMar, Sanofi, Spectrum Pharmaceuticals, Takeda, Tiziana Pharma, outside the submitted work; DP reports personal fees from AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly, Merck, Novartis, Pfizer, Prime Oncology, Peer CME, Roche, Samsung, outside the submitted work; and clinical trials research (as principal investigator or co-investigator): AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, Merck, Novartis, Pfizer, Roche, Medimmune, Sanofi-Aventis, Taiho Pharma, Novocure, Daiichi Sankyo. MR reports personal fees from Amgen, AstraZeneca, Boehringer Ingelheim, BMS, Lilly, Merck, MSD, MIRATI, MSD, Pfizer, Roche, Samsung, outside the submitted work. J-CS reports personal fees from AstraZeneca, GSK, Astex, Clovis, Genmab, Lilly, MSD, Servier, Mission Therapeutics, MERUS, Pfizer, PharmaMar, Roche, Pierre Fabre, Sanofi, Symphogen, Takeda, outside the submitted work; and has been a full-time employee of AstraZeneca between September 2017 and January 2020. He is a shareholder of AstraZeneca and Gritstone. All other authors have declared no conflicts of interest.
(Copyright © 2021 European Society for Medical Oncology. Published by Elsevier Ltd. All rights reserved.)