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

Turner NC, Laird AD, Telli ML, Rugo HS, Mailliez A, Ettl J, Grischke EM, Mina LA, Balmaña J, Fasching P, Hurvitz SA, Hopkins JF, Albacker LA, Chelliserry J, Chen Y, Conte U, Wardley AM, Robson ME (2023)

Publication Type: Journal article

Publication year: 2023

Journal

npj Breast Cancer Nature Research

Book Volume: 9

Article Number: 81

Journal Issue: 1

DOI: 10.1038/s41523-023-00561-y

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.

Authors with CRIS profile

Peter Fasching Professur für Translationale Frauenheilkunde und Geburtshilfe

Involved external institutions

Royal Marsden Hospital / The Royal Marsden NHS Foundation Trust GB United Kingdom (GB) Cardiovascular Research Foundation US United States (USA) (US) Stanford University US United States (USA) (US) UCSF Helen Diller Family Comprehensive Cancer Center US United States (USA) (US) Centre Oscar Lambret (UNICANCER) FR France (FR) Klinikum rechts der Isar DE Germany (DE) Eberhard Karls Universität Tübingen DE Germany (DE) Banner MD Anderson Cancer Center US United States (USA) (US) Autonomous University of Barcelona (UAB) / Universitat Autònoma de Barcelona ES Spain (ES) University of California Los Angeles (UCLA) US United States (USA) (US) Foundation Medicine Inc US United States (USA) (US) University of Manchester GB United Kingdom (GB) Memorial Sloan Kettering Cancer Center US United States (USA) (US)

How to cite

APA:

Turner, N.C., Laird, A.D., Telli, M.L., Rugo, H.S., Mailliez, A., Ettl, J.,... Robson, M.E. (2023). Genomic analysis of advanced breast cancer tumors from talazoparib-treated gBRCA1/2mut carriers in the ABRAZO study. npj Breast Cancer, 9(1). https://dx.doi.org/10.1038/s41523-023-00561-y

MLA:

Turner, Nicholas C., et al. "Genomic analysis of advanced breast cancer tumors from talazoparib-treated gBRCA1/2mut carriers in the ABRAZO study." npj Breast Cancer 9.1 (2023).

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