Lurbinectedin, a selective inhibitor of oncogenic transcription, in patients with pretreated germline BRCA1/2 metastatic breast cancer: results from a phase II basket study.

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Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_B3A5E089EDDA
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Lurbinectedin, a selective inhibitor of oncogenic transcription, in patients with pretreated germline BRCA1/2 metastatic breast cancer: results from a phase II basket study.
Journal
ESMO open
Author(s)
Boni V., Pistilli B., Braña I., Shapiro G.I., Trigo J., Moreno V., Castellano D., Fernández C., Kahatt C., Alfaro V., Siguero M., Zeaiter A., Longo F., Zaman K., Antón A., Paredes A., Huidobro G., Subbiah V.
ISSN
2059-7029 (Electronic)
ISSN-L
2059-7029
Publication state
Published
Issued date
10/2022
Peer-reviewed
Oui
Volume
7
Number
5
Pages
100571
Language
english
Notes
Publication types: Clinical Trial, Phase II ; Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
Publication Status: ppublish
Abstract
Lurbinectedin, a selective inhibitor of oncogenic transcription, has shown preclinical antitumor activity against homologous recombination repair-deficient models and preliminary clinical activity in BRCA1/2 breast cancer.
This phase II basket multitumor trial (NCT02454972) evaluated lurbinectedin 3.2 mg/m <sup>2</sup> 1-h intravenous infusion every 3 weeks in a cohort of 21 patients with pretreated germline BRCA1/2 breast cancer. Patients with any hormone receptor and human epidermal growth factor receptor 2 status were enrolled. The primary efficacy endpoint was overall response rate (ORR) according to RECIST v1.1. Secondary endpoints included duration of response (DoR), progression-free survival (PFS), overall survival (OS) and safety.
Confirmed partial response (PR) was observed in six patients [ORR = 28.6%; 95% confidence interval (CI) 11.3% to 52.2%] who had received a median of two prior advanced chemotherapy lines. Lurbinectedin was active in both BRCA mutations: four PRs in 11 patients (36.4%) with BRCA2 and two PRs in 10 patients (20.0%) with 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 10 patients (47.6%), including 3 with unconfirmed response in a subsequent tumor assessment [ORR unconfirmed = 42.9% (95% CI 21.8% to 66.0%)]. Clinical benefit rate (PR + SD ≥ 4 months) was 76.2% (95% CI 52.8% to 91.8%). No objective response was observed among patients who had received prior poly (ADP-ribose) polymerase inhibitors. The most common treatment-related adverse events (AEs) were nausea (61.9%), fatigue (38.1%) and vomiting (23.8%). These AEs were mostly grade 1/2. The most common grade 3/4 toxicity was neutropenia (42.9%: grade 4, 23.8%: with no febrile neutropenia).
This phase II study met its primary endpoint and showed activity of lurbinectedin in germline BRCA1/2 breast cancer. Lurbinectedin showed a predictable and manageable safety profile. Considering the exploratory aim of this trial as well as previous results in other phase II studies, further development of lurbinectedin in this indication is warranted.
Keywords
Humans, Female, Breast Neoplasms/drug therapy, Breast Neoplasms/genetics, Breast Neoplasms/pathology, Genes, BRCA2, Genes, BRCA1, Ribose/therapeutic use, Germ-Line Mutation, Poly(ADP-ribose) Polymerase Inhibitors/pharmacology, Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use, Germ Cells/pathology, Neutropenia/drug therapy, Hormones/therapeutic use, Adenosine Diphosphate/therapeutic use, BRCA1 Protein/genetics, BRCA1, BRCA2, breast cancer, lurbinectedin, phase II, response rate
Pubmed
Web of science
Open Access
Yes
Create date
05/09/2022 8:10
Last modification date
23/01/2024 7:32
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