ABSTRACT
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.
