Lurbinectedin produced responses in 35.2% of 105 patients with relapsed small-cell lung cancer.

  • Major Finding: Lurbinectedin produced responses in 35.2% of 105 patients with relapsed small-cell lung cancer.

  • Concept: Chemotherapy-resistant patients, who have dismal prognosis, also showed responses (albeit lesser).

  • Impact: This oncogenic-transcription inhibitor is promising for these patients, who have few options.

There are few treatment options for relapsed small-cell lung cancer (SCLC), with the only FDA-approved second-line therapy for SCLC being topotecan, a drug that yields responses in only 16% of relapsed patients and produces a median overall survival (OS) of 6 to 8 months. Trigo, Subbiah, and colleagues performed a single-arm, open-label, phase II basket trial of lurbinectedin, an inhibitor of the oncogenic transcription upon which SCLC depends, as a single-agent second-line treatment in 105 patients with SCLC. Among all patients, the overall response rate (ORR) was 35.2%, with all responses being partial, and the median duration of response (DOR) was 5.3 months. A preplanned analysis revealed that patients with chemotherapy-free intervals of 90 or more days fared best, with an ORR of 45.0% and a median DOR of 5.1 months. The median OS among all patients was 9.3 months, whereas the median OS was 11.9 months in patients with a chemotherapy-free interval of 90 days or longer and 5.0 months in patients with a chemotherapy-free interval of fewer than 90 days. Although the median OS was much shorter in patients with chemotherapy-resistant disease, these patients are generally considered to have a very poor prognosis regardless of treatment. Lurbinectedin was generally well tolerated: Only 2.0% of patients discontinued treatment due to treatment-related adverse events, and no treatment-related deaths occurred. Hematologic disorders were the most common grade 3 to 4 adverse events, and lower-grade adverse events were generally constitutional symptoms, such as fatigue, nausea, and decreased appetite. Limitations of the study include the lack of a control arm and the inclusion criteria, which did not allow patients with brain metastases or severe side effects from prior therapies to participate. In summary, this trial provides evidence that lurbinectedin is safe and exhibits promising evidence of efficacy in patients with relapsed SCLC, providing a new potential treatment option for a patient population that has seen only one drug approved in the past 20 years.

Trigo J, Subbiah V, Besse B, Moreno V, López R, Sala MA, et al. Lurbinectedin as second-line treatment for patients with small-cell lung cancer: a single-arm, open-label, phase 2 basket trial. Lancet Oncol 2020;21:645–54.

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