학술논문
Genomic analysis of advanced breast cancer tumors from talazoparib-treated gBRCA1/2mut carriers in the ABRAZO study
Document Type
article
Author
Nicholas C. Turner; A. Douglas Laird; Melinda L. Telli; Hope S. Rugo; Audrey Mailliez; Johannes Ettl; Eva-Maria Grischke; Lida A. Mina; Judith Balmaña; Peter A. Fasching; Sara A. Hurvitz; Julia F. Hopkins; Lee A. Albacker; Jijumon Chelliserry; Ying Chen; Umberto Conte; Andrew M. Wardley; Mark E. Robson
Source
npj Breast Cancer, Vol 9, Iss 1, Pp 1-9 (2023)
Subject
Language
English
ISSN
2374-4677
Abstract
Abstract These analyses explore the impact of homologous recombination repair gene mutations, including BRCA1/2 mutations and homologous recombination deficiency (HRD), on the efficacy of the poly(ADP-ribose) polymerase (PARP) inhibitor talazoparib in the open-label, two-cohort, Phase 2 ABRAZO trial in germline BRCA1/2-mutation carriers. In the evaluable intent-to-treat population (N = 60), 58 (97%) patients harbor ≥1 BRCA1/2 mutation(s) in tumor sequencing, with 95% (53/56) concordance between germline and tumor mutations, and 85% (40/47) of evaluable patients have BRCA locus loss of heterozygosity indicating HRD. The most prevalent non-BRCA tumor mutations are TP53 in patients with BRCA1 mutations and PIK3CA in patients with BRCA2 mutations. BRCA1- or BRCA2-mutated tumors show comparable clinical benefit within cohorts. While low patient numbers preclude correlations between HRD and efficacy, germline BRCA1/2 mutation detection from tumor-only sequencing shows high sensitivity and non-BRCA genetic/genomic events do not appear to influence talazoparib sensitivity in the ABRAZO trial. ClinicalTrials.gov identifier: NCT02034916.