1. Genomic analysis of advanced breast cancer tumors from talazoparib-treated gBRCA1/2mut carriers in the ABRAZO study.
- Author
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Turner, Nicholas, Laird, A, Telli, Melinda, Rugo, Hope, Mailliez, Audrey, Ettl, Johannes, Grischke, Eva-Maria, Mina, Lida, Balmaña, Judith, Fasching, Peter, Hurvitz, Sara, Hopkins, Julia, Albacker, Lee, Chelliserry, Jijumon, Chen, Ying, Conte, Umberto, Wardley, Andrew, and Robson, Mark
- 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.
- Published
- 2023