Clin Cancer Res. 2022 Apr 29. pii: clincanres.0696.2022. [Epub ahead of print]
Vivek Subbiah,
Irene Brana,
Alessandra Longhi,
Valentina Boni,
Jean-Pierre Delord,
Ahmad Awada,
Pascaline Boudou-Rouquette,
John Sarantopoulos,
Geoffrey I Shapiro,
Anthony Elias,
Ravin Ratan,
Cristian Fernandez,
Carmen Kahatt,
Martin Cullell-Young,
Mariano Siguero,
Ali Zeaiter,
Sant P Chawla.
PURPOSE: Lurbinectedin suppresses the oncogenic transcription factor EWS-FLI1 through relocalization to the nucleolus, and delays tumor growth in mice bearing Ewing sarcoma xenografts. Based on this rationale, lurbinectedin was evaluated in patients with relapsed Ewing sarcoma (ES).PATIENTS AND METHODS: This open-label, single-arm, Basket phase II trial included a cohort of 28 treated adult patients with confirmed ES, measurable disease as per Response Evaluation Criteria In Solid Tumors (RECIST) v.1.1, Eastern Cooperative Oncology Group performance status {less than or equal to}2, adequate organ function, no central nervous system metastasis, and pre-treated with {less than or equal to}2 chemotherapy lines for metastatic/recurrent disease. Patients received lurbinectedin 3.2 mg/m2 as a 1-hour infusion every 3 weeks. Primary endpoint was overall response rate (ORR) as per RECIST v.1.1. Secondary endpoints included time-to-event parameters and safety profile.
RESULTS: ORR was 14.3% (95% confidence interval [CI], 4.0-32.7%), with median duration of response of 4.2 months (95%CI, 2.9-5.5 months). Median progression-free survival was 2.7 months (95%CI, 1.4-4.3 months), clinical benefit rate was 39.3% and disease control rate was 57.1%. With 39% censoring, median overall survival was 12.0 months (95%CI, 8.5-18.5 months). Most common grade 3/4 adverse events were neutropenia (57%), anemia, thrombocytopenia, and treatment-related febrile neutropenia (14% each). No deaths or discontinuations were due to toxicity.
CONCLUSIONS: Lurbinectedin was active in the treatment of relapsed ES and had a manageable safety profile. Lurbinectedin could represent a valuable addition to therapies for ES, and is currently being evaluated in combination with irinotecan in advanced ES in a phase Ib/II trial.