Lurbinectedin for Second-Line Treatment of Patients with Metastatic SCLC

Lurbinectedin is an effective second-line treatment for patients with advanced SCLC who have progressed after platinum-based chemotherapy.

There are few treatment options for patients with SCLC who progress after first-line platinum-containing therapy regimens.¹ A phase 2 study was conducted to evaluate the activity and safety of lurbinectedin (Zepzelca), a selective inhibitor of oncogenic transcription, in patients with SCLC who progressed after receiving platinum-based chemotherapy.¹

This single-arm, open-label, phase 2 basket trial enrolled adult patients in Europe and the United States who had a pathologically proven diagnosis of SCLC, ECOG performance status of ≤2, measurable disease per RECIST version 1.1, no brain metastasis, and adequate organ function.¹ These patients received treatment with only 1 previous chemotherapy-containing regimen before study initiation.¹

Treatment consisted of lurbinectedin (3.2 mg/m²) administered as a 1-hour intravenous infusion every 3 weeks until disease progression or unacceptable toxicity.¹ The primary outcome of this study was the proportion of patients with an ORR, including complete or partial response, as assessed by investigators using RECIST criteria.¹

Between October 2015 and January 2019, 105 patients with progressive SCLC were enrolled and treated with lurbinectedin. After median follow-up of 17.1 months, the ORR determined by investigator assessment was 35% (95% CI, 26%-45%).¹ Median DOR was 5.3 months (95% CI, 4.1-6.4).² Per independent review committee, the ORR was 30% (95% CI, 22%-40%) with median DOR of 5.1 months (95% CI, 4.9-6.4).²

The most common AEs (≥20%) were myelosuppression, fatigue, nausea, decreased appetite, musculoskeletal pain, constipation, dyspnea, vomiting, cough, and diarrhea.² The most common grade 3 and 4 AEs included hematologic abnormalities, specifically neutropenia (46%), leukopenia (29%), anemia (9%), and thrombocytopenia (7%).¹ Serious treatment-related AEs occurred in 10% of patients; neutropenia and febrile neutropenia were most frequent (5% each). No treatment-related deaths were reported.¹

Researchers concluded that lurbinectedin is active as second-line therapy for SCLC in terms of ORR and had an acceptable and manageable safety profile.¹ In June 2020, the US Food and Drug Administration granted lurbinectedin accelerated approval as a new treatment for patients with advanced SCLC who have progressed after platinum-based chemotherapy.²

References
1. Trigo J, Subbiah V, Besse B, 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;21:645-654.
2. US Food and Drug Administration. FDA grants accelerated approval to lurbinectedin for metastatic small cell lung cancer. June 16, 2020. www.fda.gov/drugs/drug-approvals-and-databases/fda-grants-accelerated-approval-lurbinectedin-metastatic-small-cell-lung-cancer. Accessed November 29, 2020.