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The current and emerging immunotherapy paradigm in small-cell lung cancer

Nature Cancer volume 6, pages 954–966 (2025)Cite this article

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Abstract

Small-cell lung cancer (SCLC) is a highly aggressive malignancy with poor prognosis. For decades, etoposide–platinum-based chemotherapy had been the mainstay treatment for SCLC; however, despite initial high response rates, most patients developed resistance. In 2019, the US Food and Drug Administration approved the anti-PD-L1 antibody atezolizumab in combination with etoposide–platinum as the new first-line standard of care for extensive-stage SCLC, heralding a paradigm shift in SCLC therapy. This Review aims to provide an overview of the current landscape and emerging treatment strategies of immunotherapies in SCLC as well as highlight the importance of developing biomarkers to facilitate patient selection.

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Fig. 1: Different types of immunotherapies and their representative therapeutic agents for SCLC.

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Acknowledgements

The work of the authors is supported by a Barbanti Small Cell Lung Cancer Award, University of Texas MD Anderson Physician Scientist Award, University Cancer Foundation Sister Institution Network Fund, National Institutes of Health (NIH)/NCI U01-CA213273, NIH/NCI U01-CA256780-01, the LUNGevity Foundation, Rexanna’s Foundation for Fighting Lung Cancer, the Andrew Sabin Family Foundation, Cancer Prevention Research Institute of Texas, the University of Texas MD Anderson Lung Cancer Moon Shot Program, The University of Texas Lung SPORE Program, the University of Texas MD Anderson Lung Cancer Genomics Program, the University of Texas MD Anderson Lung Cancer Interception Program, and the generous support from the Andrea Mugnaini and Edward LC Smith Fund. We thank C. Hu, Z. H. Kwok and J. Li from Helius for their support during preparation of this Review.

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Author notes

  1. These authors contributed equally: Kang Qin, Carl M. Gay.

  2. These authors jointly supervised this work: Lauren A. Byers, Jianjun Zhang.

Authors and Affiliations

  1. Department of Thoracic/Head & Neck Medical Oncology, the University of Texas, MD Anderson Cancer Center, Houston, TX, USA

    Kang Qin, Carl M. Gay, Lauren A. Byers & Jianjun Zhang

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Contributions

J.Z. and L.B. jointly supervised the preparation of this manuscript. K.Q. and C.M.G. contributed their clinical and translational expertise on the topic.

Corresponding authors

Correspondence to Lauren A. Byers or Jianjun Zhang.

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Competing interests

C.M.G. serves on advisory committees for Abdera, AstraZeneca, BMS, Daiichi Sankyo, G1, Jazz, MonteRosa, Roche/Genentech and reports Speaking Engagement from AstraZeneca, BeiGene, MJH, OncLive, PeerView, Targeted Healthcare, and receives Paid Consulting from Catalyst, Kisoji, STCube. L.A.B. serves on advisory committees for AstraZeneca, AbbVie, Genetech, Amgen, Daiichi Sankyo, Novartis and has research support from AstraZeneca, Amgen. J.Z. reports grants from Merck and Helius, grants and personal fees from Johnson and Johnson and Novartis, personal fees from Bristol-Myers Squibb, AstraZeneca, GenePlus, Innovent, Varian, Catalyst and Hengrui outside the submitted work. K.G. declares no competing interests.

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Qin, K., Gay, C.M., Byers, L.A. et al. The current and emerging immunotherapy paradigm in small-cell lung cancer. Nat Cancer 6, 954–966 (2025). https://doi.org/10.1038/s43018-025-00992-5

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