Lurbinectedin in the therapeutic landscape of SCLC: key clinical evidence and evolving role in the era of emerging therapies.

Authors

Andrea Monte, Elisa Andrini, Sara Stumpo, Maria Giovanna Formelli, Arianna Zappi, Anna Scognamiglio, Adriana Di Odoardo, Davide Campana, Giuseppe Lamberti

Published in

Critical reviews in oncology/hematology. Pages 105548. Aug 15, 2026. Epub Aug 15, 2026.

Abstract

Despite recent therapeutic advances, durable disease control in small cell lung cancer (SCLC) remains challenging, particularly after relapse following platinum-based chemo-immunotherapy. Lurbinectedin, a selective inhibitor of oncogenic transcription, has emerged as a novel therapeutic agent with a distinct mechanism of action combining transcription-dependent DNA damage, modulation of the tumor microenvironment, and induction of immunogenic cell death, providing a biological rationale for combination strategies with immunotherapy and other cytotoxic agents. Initially developed as a second-line treatment, lurbinectedin demonstrated clinically meaningful activity in early studies of relapsed SCLC, leading to accelerated regulatory approval. However, subsequent studies have progressively refined its role across different treatment settings. While the phase III ATLANTIS trial did not demonstrate a survival benefit for the combination of lurbinectedin and doxorubicin, emerging data have confirmed its activity and manageable safety profile across heterogeneous patient populations. More recently, the phase III IMforte trial demonstrated improved survival outcomes with maintenance lurbinectedin plus atezolizumab following induction chemo-immunotherapy, expanding its potential role beyond the relapsed setting. Understanding which patients are most likely to benefit from lurbinectedin and how best to integrate this agent into modern treatment strategies represents a key challenge in the management of SCLC. In this review, we summarize the biological rationale, key clinical evidence, and safety profile of lurbinectedin, with particular focus on clinical and molecular predictive factors of response, patient selection and its evolving role within increasingly complex SCLC treatment algorithms.

PMID:
42603642
Bibliographic data and abstract were imported from PubMed on 16 Aug 2026.

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