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FDA approves first-line combination maintenance therapy lurbinectedin and atezolizumab for extensive-stage small cell lung cancer

On October 2, 2025, the U.S. Food and Drug Administration (FDA) approved lurbinectedin and atezolizumab for adult patients with extensive-stage small cell lung cancer (ES-SCLC) in the frontline maintenance setting.1 Although both have separately been FDA approved, sufficient clinical data now supports their treatment efficacy when used in combination. Lurbinectedin, an alkylating agent previously limited to second-line use, works to disrupt the tumour cell cycle.2

SCLC comprises 15% of lung cancers, with over two-thirds of cases presenting as ES-SCLC.3 Patient prognosis, despite the recent integration of targeted immunotherapy into the treatment paradigm, remains poor, with a 5-year survival rate of 7%.4 These shortcomings highlighted the need for research into novel therapeutic agents.

Accelerated FDA approval was supported by the global randomized, multicenter, open-label Phase III IMforte study (NCT05091567), which evaluated lurbinectedin with atezolizumab versus atezolizumab alone following induction chemotherapy with carboplatin, etoposide and atezolizumab in patients with ES-SCLC. The combination regimen achieved a median progression-free survival (PFS) of 5.4 months (95% CI, 0.43-0.67) and overall survival (OS) of 13.2 months (95% CI: 0.57-0.95), compared to 2.1 months and 10.6 months, respectively, with atezolizumab monotherapy, demonstrating a statistically significant improvement in both PFS and OS. The regimen also demonstrated a generally favourable safety profile, with no new safety signals, though Grade 3-4 adverse events were more frequent with the combination (25.6% versus 5.8%), as were treatment discontinuations (6.2% versus 3.3%).5

This FDA approval progresses towards greater clinical outcomes and increased treatment options for patients with ES-SCLC. Offering improved OS and PFS, the combined maintenance therapy lurbinectedin and atezolizumab also challenges the reliance on platinum rechallenge.6 Lurbinectedin may additionally extend its impact in ES-SCLC by potentially restoring platinum sensitivity, enabling re-treatment with platinum agents and prompting further research into resistance mechanisms.

References:

  1. Center for Drug Evaluation and Research. FDA approves lurbinectedin in combination with atezolizumab [Internet]. U.S. Food and Drug Administration. 2025 [cited 2025 Oct 2]. Available from: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-lurbinectedin-combination-atezolizumab-or-atezolizumab-and-hyaluronidase-tqjs-extensive
  2. Singh S, Jaigirdar AA, Mulkey F, Cheng J, Hamed SS, Li Y, et al. FDA Approval Summary: Lurbinectedin for the Treatment of Metastatic Small Cell Lung Cancer. Clinical Cancer Research. 2020 Dec 7;27(9):2378–82.
  3. Calvo V, Carcereny Costa E, Guirado M, Ortega Granados AL, Lopez Castro R, Rodriguez-Abreu D, et al. 1794P Extensive stage (ES) small-cell lung cancer (SCLC) in Spain: A review of demographic, epidemiological and clinical data from the Thoracic Tumors Registry (TTR study). Annals of Oncology. 2020 Sep;31:S1039.
  4. Byers LA, Rudin CM. Small cell lung cancer: Where do we go from here? Cancer. 2014 Oct 21;121(5):664–72.
  5. Paz-Ares LG, Borghaei H, Liu SV, Peters S, Herbst RS, Stencel KM, et al. Lurbinectedin (lurbi) + atezolizumab (atezo) as first-line (1L) maintenance treatment (tx) in patients (pts) with extensive-stage small cell lung cancer (ES-SCLC): Primary results of the phase 3 IMforte trial. Journal of Clinical Oncology. 2025 Jun;43(16_suppl):8006–6.
  6. Dómine Gómez M, Subbiah V, Peters S, Sala MA, Trigo J, Paz-Ares L, et al. Lurbinectedin is an effective alternative to platinum rechallenge and may restore platinum sensitivity in patients with sensitive relapsed small cell lung cancer. Expert Review of Anticancer Therapy. 2024 Dec 12;25(1):27–40.