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

Nat Cancer. 2025 Jun;6(6):954-966. doi: 10.1038/s43018-025-00992-5. Epub 2025 Jun 5.

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.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • B7-H1 Antigen / antagonists & inhibitors
  • B7-H1 Antigen / immunology
  • Etoposide / administration & dosage
  • Etoposide / therapeutic use
  • Humans
  • Immune Checkpoint Inhibitors / therapeutic use
  • Immunotherapy* / methods
  • Immunotherapy* / trends
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / immunology
  • Lung Neoplasms* / pathology
  • Lung Neoplasms* / therapy
  • Small Cell Lung Carcinoma* / drug therapy
  • Small Cell Lung Carcinoma* / immunology
  • Small Cell Lung Carcinoma* / pathology
  • Small Cell Lung Carcinoma* / therapy

Substances

  • Antibodies, Monoclonal, Humanized
  • atezolizumab
  • Immune Checkpoint Inhibitors
  • B7-H1 Antigen
  • Etoposide
  • CD274 protein, human