REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
This article is part of the Research TopicCommunity Series in Unveiling the Next Generation of Cancer Immunity & Immunotherapy in Lung Cancer: Volume IIView all 9 articles
Expanding the Immunotherapy Universe in Extensive-Stage Small Cell Lung Cancer: From Chemoimmunotherapy Backbone to Next-Wave Combinations
Provisionally accepted
- 1Affiliated Hospital to Changchun University of Chinese Medicine, Changchun, China
- 2Tong Hua City Hospital of Chinese Medicine, Tonghua, China
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Small-cell lung cancer (SCLC) is a highly malignant neuroendocrine tumor characterized by rapid proliferation and dismal prognosis. Platinum-based chemotherapy combined with immune checkpoint inhibitors (ICIs) is now the first-line treatment for extensive-stage disease (ES-SCLC), extending the overall survival (OS) period of these patients by 2-5 months, yet durable remissions remain the privilege of fewer than 20 % of patients. Despite intensive investigation, this incremental benefit appears to have plateaued, prompting exploration of alternative combination strategies to unleash deeper and more durable antitumor synergy. Recent phase II/III trials integrating anti-angiogenic agents into the chemo-immunotherapy have reported unprecedented OS gains of up to 7 months, redefining therapeutic expectations. Concurrently, chemoradiation with ICIs triplet regimens have demonstrated encouraging antitumor activity in ES-SCLC, while rational combinations of small-molecule targeted drugs (DLL3 inhibitors, PARP inhibitors) combined with ICIs or epigenetic modifiers with ICIs are yielding early signals of efficacy. Nevertheless, primary resistance, absence of robust predictive biomarkers, and cumulative toxicity continue to curtail clinical impact. This Review provides a comprehensive, evidence-based map of the evolving ES-SCLC immunotherapy combination landscape. We critically dissect competing therapeutic paradigms, juxtapose corroborative and contradictory data, and distill actionable insights for future trial design, biomarker development, and regulatory strategy.
Keywords: Extensive-stage small cell lung cancer, Immunotherapy combinations, Anti-angiogenic agents, Radiotherapy, targeted therapy, emerging research
Received: 27 Aug 2025; Accepted: 18 Nov 2025.
Copyright: © 2025 Chi, Dong, Zhu, Su and Wu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Haolin Wu, sudi880529@163.com
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