Lurbinectedin in patients with pretreated BRCA1/2-associated metastatic breast cancer: Results from a phase II basket study.

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1092 Background: Lurbinectedin (L) is a selective inhibitor of oncogenic transcription that leads to cell apoptosis and shows antitumor activity against homologous recombination repair-deficient cell lines. A previous phase II study (Cruz et al. JCO 2018;36:3134-3143) demonstrated antitumor activity in patients (pts) with pretreated metastatic breast cancer (median of 1 prior advanced chemotherapy line) and BRCA1/2-mutated tumors with L 3.5 mg/m2 or 7.0 mg flat dose (equivalent to 4.0 mg/m2) every three weeks [q3wk]). This report focuses on the outcomes in the BRCA1/2-associated breast cancer cohort of a phase II Basket multitumor trial. Methods: This phase II study evaluated L 3.2 mg/m2 1-hour intravenous (i.v.) infusion q3wk in a cohort of 21 female pts with pretreated BRCA1/2-associated breast cancer. The primary efficacy endpoint was ORR according to RECIST v1.1. Secondary endpoints included duration of response (DoR), progression-free survival (PFS), OS and safety. Results: Median age was 45 years (range, 29-73 years). Hormone receptor (HR)+ disease was observed in 76.2% of pts, triple negative disease in 19.0% and HER2+ in 9.5%. BRCA1 and BRCA2 were reported in 47.6% and 52.4% of pts, respectively. Median number of prior lines of chemotherapy for advanced disease was 2 (range, 0-3 lines). Prior poly(ADP-ribose) polymerase inhibitors and platinum compounds had been administered to 23.8% and 47.6% of pts, respectively. Confirmed partial response (PR) was observed in six pts (ORR = 28.6%; 95% CI, 11.3-52.2%). Lurbinectedin was active in both BRCA mutations: four PRs in 11 pts (36.4%) in BRCA2 and two PRs in 10 pts (20.0%) in BRCA1. Median DoR was 8.6 months, median PFS was 4.1 months and median OS was 16.1 months. Stable disease (SD) was observed in ten pts (47.6%), including three pts with unconfirmed response in a subsequent tumor assessment (ORR unconfirmed = 42.9% [95%CI, 21.8-66.0]). Clinical benefit rate (PR + SD≥4 months) was 76.2% (95% CI, 52.8-91.8%). The most common grade 3/4 toxicity was neutropenia (42.9%; grade 4, 23.8%; with no febrile neutropenia). Conclusions: This phase II study met its primary endpoint and confirmed the activity of L in pretreated BRCA1/2-associated breast cancer pts. L 3.2 mg/m2 1-hour i.v. infusion q3wk showed an acceptable, predictable and manageable safety profile. Considering the exploratory aim of this trial as well as previous results in other phase II study, further development of L in this indication is warranted. Clinical trial information: NCT02454972.