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Lurbinectedin in BRCA-Mutated and Unselected Metastatic Breast Cancer

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Key Points

  • The response rate was 41% in the BRCA-mutant group, including 61% among patients with BRCA2 mutation and 26% among those with BRCA1 mutation.
  • The response rate in the BRCA wild-type/unknown status group was 9%.

In a phase II study reported in the Journal of Clinical Oncology, Cruz et al found that the trabectedin (Yondelis) analog lurbinectedin was active in patients with metastatic breast cancer with germline BRCA mutations, with much lower activity in those without BRCA mutation or unknown mutation status. Lurbinectedin is a selective inhibitor of active transcription of protein-coding genes.

Study Details

In the study, 54 patients with BRCA1/2 mutation and 35 patients with BRCA1/2 wild-type (n = 9) or unknown status received lurbinectedin via 1-hour infusion every 3 weeks, initially at a flat dose of 7.0 mg; after evidence of body surface area–related toxicity was observed, dosing was changed to 3.5 mg/m2 (received by 19 patients in the BRCA-mutant group).

Response Rates

In the BRCA-mutant group, the objective response rate was 41%, including 61% among 23 patients with BRCA2 mutation and 26% among 31 with BRCA1 mutation. Median progression-free survival was 4.6 months, including 5.9 months in those with BRCA2 mutation and 3.0 months in those with BRCA1 mutation. Median overall survival was 20, 26.6, and 15.9 months, respectively.

In the wild-type/unknown status group, the objective response rate was 9% and median progression-free and overall survival were 2.5 months and 12.5 months, respectively.

Adverse Events

Severe adverse events and laboratory abnormalities were reduced in frequency with the switch to a dose of 3.5 mg/m2, including a reduction in grade 4 neutropenia from 51% to 10% in the BRCA-mutant group. The most common nonhematologic adverse events observed at 3.5 mg/m2 were nausea (74%, 5% grade 3), and fatigue (74%, 21% grade 3). Neutropenia was the most common severe hematologic adverse event (47% grade 3, 10% grade 4).

The investigators concluded, “Lurbinectedin showed noteworthy activity in patients with BRCA1/2 mutations. Response and survival was notable in those with BRCA2 mutations. Additional clinical development in this subset of patients with metastatic breast cancer is warranted.”

The study was supported by grants and fellowships from the Asociación Española Contra el Cóncer, Health Department of Generalitat de Catalunya, Breast Cancer Research Foundation.

Judith Balmaña, MD, PhD, of Vall d’Hebron Institute of Oncology, is the corresponding author for the Journal of Clinical Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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