Lurbinectedin as second-line treatment for patients with small-cell lung cancer: a single-arm, open-label, phase 2 basket trial

José Trigo, Vivek Subbiah, Benjamin Besse, Victor Moreno, Rafael López, María Angeles Sala, Solange Peters, Santiago Ponce, Cristian Fernández, Vicente Alfaro, Javier Gómez, Carmen Kahatt, Ali Zeaiter, Khalil Zaman, Valentina Boni, Jennifer Arrondeau, Maite Martínez, Jean Pierre Delord, Ahmad Awada, Rebecca KristeleitMaria Eugenia Olmedo, Luciano Wannesson, Javier Valdivia, María Jesús Rubio, Antonio Anton, John Sarantopoulos, Sant P. Chawla, Joaquín Mosquera-Martinez, Manolo D'Arcangelo, Armando Santoro, Victor M. Villalobos, Jacob Sands, Luis Paz-Ares

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121 Scopus citations


Background: Few options exist for treatment of patients with small-cell lung cancer (SCLC) after failure of first-line therapy. Lurbinectedin is a selective inhibitor of oncogenic transcription. In this phase 2 study, we evaluated the acti and safety of lurbinectedin in patients with SCLC after failure of platinum-based chemotherapy. Methods: In this single-arm, open-label, phase 2 basket trial, we recruited patients from 26 hospitals in six European countries and the USA. Adults (aged ≥18 years) with a pathologically proven diagnosis of SCLC, Eastern Cooperative Oncology Group performance status of 2 or lower, measurable disease as per Response Criteria in Solid Tumors (RECIST) version 1.1, absence of brain metastasis, adequate organ function, and pre-treated with only one previous chemotherapy-containing line of treatment (minimum 3 weeks before study initiation) were eligible. Treatment consisted of 3·2 mg/m2 lurbinectedin administered as a 1-h intravenous infusion every 3 weeks until disease progression or unacceptable toxicity. The primary outcome was the proportion of patients with an overall response (complete or partial response) as assessed by the investigators according to RECIST 1.1. All treated patients were analysed for activity and safety. This study is ongoing and is registered with, NCT02454972. Findings: Between Oct 16, 2015, and Jan 15, 2019, 105 patients were enrolled and treated with lurbinectedin. Median follow-up was 17·1 months (IQR 6·5–25·3). Overall response by investigator assessment was seen in 37 patients (35·2%; 95% CI 26·2–45·2). The most common grade 3–4 adverse events (irrespective of causality) were haematological abnormalities—namely, anaemia (in nine [9%] patients), leucopenia (30 [29%]), neutropenia (48 [46%]), and thrombocytopenia (seven [7%]). Serious treatment-related adverse events occurred in 11 (10%) patients, of which neutropenia and febrile neutropenia were the most common (five [5%] patients for each). No treatment-related deaths were reported. Interpretation: Lurbinectedin was active as second-line therapy for SCLC in terms of overall response and had an acceptable and manageable safety profile. Lurbinectedin could represent a potential new treatment for patients with SCLC, who have few options especially in the event of a relapse, and is being investigated in combination with doxorubicin as second-line therapy in a randomised phase 3 trial. Funding: Pharma Mar.

Original languageEnglish (US)
Pages (from-to)645-654
Number of pages10
JournalThe Lancet Oncology
Issue number5
StatePublished - May 2020

ASJC Scopus subject areas

  • Oncology


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