Lurbinectedin in patients with small cell lung cancer with chemotherapy-free interval ≥30 days and without central nervous metastases

Abstract

Chemotherapy-free interval; Lurbinectedin; Response rate

Interval lliure de quimioteràpia; Lurbinectedina; Taxa de resposta

Intervalo libre de quimioterapia; Lurbinectedina; Tasa de respuesta

Objectives This report focuses on lurbinectedin activity and safety in a subgroup of small cell lung cancer (SCLC) patients from a Basket phase 2 study (Trigo et al. Lancet Oncology 2020;21:645–654) with chemotherapy-free interval (CTFI) ≥ 30 days. This pre-planned analysis was requested for obtaining regulatory approval of lurbinectedin in Switzerland. Materials and methods Patients with extensive-stage SCLC, no central nervous system (CNS) metastases, and disease progression after platinum-containing therapy were included. Topotecan data from a contemporary, randomized, controlled phase 3 study (ATLANTIS) were used as indirect external control in a matched patient population (n = 98 patients). Results Lurbinectedin showed a statistically significant higher overall response rate (ORR) by investigator assessment (IA) compared to topotecan subgroup (41.0 % vs. 25.5 %; p = 0.0382); higher ORR by Independent Review Committee (IRC) (33.7 % vs. 25.5 %); longer median duration of response (IA: 5.3 vs. 3.9 months; IRC: 5.1 vs. 4.3 months), and longer median overall survival (10.2 vs. 7.6 months). Grade ≥ 3 hematological abnormalities were remarkably lower with lurbinectedin: anemia 12.0 % vs. 54.1 %; leukopenia 30.1 % vs. 68.4 %; neutropenia 47.0 % vs. 75.5 %, and thrombocytopenia 6.0 % vs. 52.0 %. Febrile neutropenia was observed at a higher incidence with topotecan (6.1 % vs. 2.4 % with lurbinectedin) despite that the use of growth-colony stimulating factors was mandatory with topotecan. Conclusion With the limitations of an indirect comparison, however using recent and comparable SCLC datasets, this post hoc analysis shows that SCLC patients with CTFI ≥ 30 days and no CNS metastases have a positive benefit/risk ratio with lurbinectedin, superior to that observed with topotecan.

The study was funded by Pharma Mar S.A with grants from the Centro para el Desarrollo Tecnológico Industrial (CDTI) during the conduct of the study.