Journal Article

Genomic analysis of advanced breast cancer tumors from talazoparib-treated gBRCA1/2mut carriers in the ABRAZO study

Telli, Melinda L, Rugo, Hope S, Laird, A. Douglas, Mina, Lida A, Chen, Ying, Fasching, Peter A, Hopkins, Julia F, Mailliez, Audrey, Albacker, Lee A, Chelliserry, Jijumon, Conte, Umberto, Grischke, Eva-Maria, Balmaña, Judith, Robson, Mark E, Hurvitz, Sara A, Ettl, Johannes, Wardley, Andrew M, Turner, Nicholas C

2023

Overview

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.

• Publisher: Nature Publishing Group
• Subject: Breast cancer / Cancer research / DNA methylation / Drug dosages / Genes / Gynecology / Medical research / Mutation / Obstetrics / Oncology / Patients / Tumors