Lurbinectedin Shows Superiority to Topotecan in Small Cell Lung Cancer


Findings from a post hoc analysis of lurbinectedin for the treatment of small cell lung cancer showed that the agent was more effective and less toxic than topotecan.

Small cell lung cancer: ©Dr_Micobe -

Small cell lung cancer: ©Dr_Micobe -

Patients with small cell lung cancer (SCLC) who had a chemotherapy-free interval of 30 days or longer with no central nervous system (CNS) metastases experienced a positive benefit-to-risk ratio of treatment with lurbinectedin (Zepzelca) vs topotecan, according to a post hoc analysis.

The analysis, which was requested for lurbinectedin’s regulatory approval in Switzerland, demonstrated that lurbinectedin had a statistically significant overall response rate (ORR) by investigator assessment of 41% compared with 25.5% in the topotecan control group referenced from the phase 3 ATLANTIS study (NCT02566993; P = .0382). The ORR by independent review was 33.7% for lurbinectedin vs 25.5% with topotecan.

Lurbinectedin also demonstrated higher median duration of response compared with topotecan (independent review, 5.1 vs 4.3 months; investigator assessment, 5.3 vs 3.9 months). The median overall survival in the lurbinectedin group was 10.2 months vs 7.6 months in the topotecan group.

“Lurbinectedin is more active, as measured by all usual outcomes metrics, and is clearly less toxic and better tolerated than topotecan. An ongoing confirmatory phase 3 trial [LAGOON; NCT05153239] is evaluating lurbinectedin as single agent or in combination with irinotecan vs topotecan or irinotecan in the population of adult SCLC patients who have failed one prior platinum-containing line with [a chemotherapy-free interval] ≥ 30 days and controlled asymptomatic CNS metastases,” study authors wrote in An International Journal for Lung Cancer and other Thoracic Malignancies.

The analysis was conducted between October 2015 and November 2020, and the referenced ATLANTIS study occurred between August 2016 and November 2020. The matched populations had similar median ages: 60 years in the lurbinectedin group vs 63 years in the topotecan group.

Safety of Lurbinectedin vs Topotecan in Small Cell Lung Cancer

Regarding safety, grade 3 or lower hematological abnormalities were less frequently observed with lurbinectedin vs topotecan and were mainly 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%). Topotecan was associated with a higher rate of febrile neutropenia compared with lurbinectedin (6.1% vs 2.4%).

Grade 3 or lower adverse events (AEs) were also notably observed less in patients treated with lurbinectedin vs topotecan (55.4% vs 90.8%). For treatment-related AEs, the incidence with lurbinectedin was 41.0% vs 82.7% with topotecan. The most common AEs were fatigue and gastrointestinal events, and alopecia was only observed with topotecan.

“A favorable safety profile was observed in this post hoc analysis for lurbinectedin compared to topotecan, especially for hematological toxicities… This advantageous safety profile of lurbinectedin may help to counteract the significant health resources consumption observed in patients with relapsed SCLC treated with topotecan,” study authors wrote.

Peters S, Trigo J, Besse B, et al. Lurbinectedin in patients with small cell lung cancer with chemotherapy-free interval ≥30 days and without central nervous metastases. Lung Canc. 2024;188:107448. doi:10.1016/j.lungcan.2023.107448
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