In:
npj Breast Cancer, Springer Science and Business Media LLC, Vol. 9, No. 1 ( 2023-10-06)
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.
Type of Medium:
Online Resource
ISSN:
2374-4677
DOI:
10.1038/s41523-023-00561-y
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2023
detail.hit.zdb_id:
2843288-5