Abstract 2575
Background
Loss-of-function mutations in genes encoding components of the homologous recombination (HR) machinery are associated with tumor sensitivity to poly (ADP-ribose) polymerase (PARP) inhibitors. In ABRAZO, the PARP inhibitor talazoparib demonstrated encouraging efficacy in gBRCA-mutated ABC, both in pts whose cancer responded to prior platinum therapy (cohort 1) and in pts who had received ≥3 prior nonplatinum chemotherapy regimens for ABC (cohort 2).
Methods
Baseline tumor tissue (primary or metastatic sites) from enrolled pts was sequenced using the FoundationOne CDx NGS panel. 60/84 pts (71%) in the intent-to-treat population had available tumor tissue, which could be sequenced. Mutations summarized below were known or likely pathogenic single-nucleotide variants, insertions, deletions, or rearrangements. Additional exploratory computational analyses pertinent to HR deficiency were performed, including genomic loss of heterozygosity (gLOH) and somatic-germline-zygosity assessments.
Results
Tumor mutations in BRCA1 and BRCA2 were detected in 29 (48%) and 28 (47%) of 60 evaluable pts (no pts exhibited mutations in both BRCA1 and BRCA2). These mutations were most commonly single-nucleotide variants (BRCA1: 12 [20%] and BRCA2: 10 [17%]) or deletions (BRCA1: 11 [18%] and BRCA2: 12 [20%]). Mutations in other genes implicated in HR were comparatively rare, with mutations in CHEK2 (2 pts), ARID1A, ATR, BARD1, BRD4, BRIP1, FANCC, and STAG2 (each in single pts) detected. In addition to BRCA1/2, genes where mutations were detected in ≥ 10% of evaluable pts included TP53 (45%) and PIK3CA (12%). TP53 mutations were more commonly observed in BRCA1-mutated than in BRCA2-mutated tumors (22/29 [76%] compared with 4/28 [14%]). Associations of genetic/genomic events with progression-free survival will be presented.
Conclusions
NGS of tumors from the ABRAZO study of talazoparib in patients with gBRCA-mutated ABC revealed a complex mutational landscape. Exploratory correlative analyses are ongoing and will be reported.
Clinical trial identification
NCT02034916.
Editorial acknowledgement
Legal entity responsible for the study
Pfizer Inc.
Funding
Pfizer Inc.
Disclosure
N.C. Turner: Advisory / Consultancy, Research grant / Funding (institution): Pfizer Inc.; Advisory / Consultancy, Research grant / Funding (institution): BioMarin. A..D. Laird: Full / Part-time employment: Pfizer Inc. M.L. Telli: Advisory / Consultancy, Research grant / Funding (institution): Pfizer Inc.; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Tesaro; Advisory / Consultancy, Research grant / Funding (institution): PharmaMar; Advisory / Consultancy, Research grant / Funding (institution): Vertex; Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): Biothera; Research grant / Funding (institution): Calithera Biosciences; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): Medivation; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): OncoSec; Research grant / Funding (institution): Sanofi. H.S. Rugo: Research grant / Funding (institution): Eisai; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): GSK; Research grant / Funding (institution), Travel / Accommodation / Expenses: Lilly; Research grant / Funding (institution): MacroGenics; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): OBI Pharma; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Plexxikon; Travel / Accommodation / Expenses: Mylan; Travel / Accommodation / Expenses: Puma; Research grant / Funding (institution): Eisai; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): GlaxoSmithKline; Research grant / Funding (institution), Travel / Accommodation / Expenses: Lilly; Research grant / Funding (institution): MacroGenics; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): OBI Pharma; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Plexxikon; Travel / Accommodation / Expenses: Mylan; Travel / Accommodation / Expenses: Puma. A. Mailliez: Honoraria (self), Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Tesaro; Advisory / Consultancy, Research grant / Funding (institution): PharmaMar; Advisory / Consultancy: Vertex; Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): Biothera; Research grant / Funding (institution): Calithera Biosciences; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): Medivation; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): OncoSec; Research grant / Funding (institution): Pfizer Inc. J. Ettl: Honoraria (institution), Advisory / Consultancy: Lilly; Advisory / Consultancy, Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Honoraria (institution), Advisory / Consultancy: Roche; Advisory / Consultancy: Tesaro; Advisory / Consultancy: Eisai; Research grant / Funding (institution), Travel / Accommodation / Expenses: Celgene; Honoraria (self): TEVA; Honoraria (self): AstraZeneca. J. Balmaña: Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZenca; Advisory / Consultancy: Clovis; Advisory / Consultancy: Tesaro; Advisory / Consultancy: BMS; Research grant / Funding (institution), Travel / Accommodation / Expenses: PharMar. P.A. Fasching: Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: Celgene; Honoraria (self), Advisory / Consultancy: Puma; Honoraria (self), Advisory / Consultancy: Daiichi Sankyo; Honoraria (self), Advisory / Consultancy: Eisai; Honoraria (self), Advisory / Consultancy: Merck; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Teva; Honoraria (self), Advisory / Consultancy: Hexal; Honoraria (institution), Speaker Bureau / Expert testimony: Myelo; Research grant / Funding (institution): BioNTech. S.A. Hurvitz: Research grant / Funding (institution): Ambryx; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): BI Pharma; Research grant / Funding (institution): Biomarin; Research grant / Funding (institution): Cascadian; Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution): Dignitana; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): GSK; Research grant / Funding (institution), Travel / Accommodation / Expenses: Lilly; Research grant / Funding (institution): Macrogenics; Research grant / Funding (institution): Medivation; Research grant / Funding (institution): Merrimack; Research grant / Funding (institution), Travel / Accommodation / Expenses: Novartis; Research grant / Funding (institution), Travel / Accommodation / Expenses: OBI Pharma; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Pieris; Research grant / Funding (institution): PUMA; Research grant / Funding (institution): Roche. L.A. Albacker: Full / Part-time employment: Foundation Medicine Inc. G.M. Frampton: Full / Part-time employment: Foundation Medicine Inc. J. Chelliserry: Shareholder / Stockholder / Stock options, Full / Part-time employment: Pfizer Inc. P. Bycott: Research grant / Funding (self), Shareholder / Stockholder / Stock options, Full / Part-time employment: Pfizer Inc. U. Conte: Shareholder / Stockholder / Stock options, Full / Part-time employment: Pfizer Inc. A.M. Wardley: Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Lilly; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Roche. M.E. Robson: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy: McKesson; Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): BioMarin; Research grant / Funding (institution): Medivation; Research grant / Funding (institution): Myriad Genetics; Research grant / Funding (institution): Tesaro. All other authors have declared no conflicts of interest.
Resources from the same session
5747 - The routine use of sentinel lymph node biopsy in high risk DCIS lesions is not justified
Presenter: Fanny Preat
Session: Poster Display session 2
Resources:
Abstract
1837 - Oncological impact of re-excision for positive margin status after breast conserving surgery in invasive breast cancer
Presenter: Kenjiro Jimbo
Session: Poster Display session 2
Resources:
Abstract
4347 - Pneumonitis and fibrosis after breast cancer radiation.
Presenter: Jarle Karlsen
Session: Poster Display session 2
Resources:
Abstract
2280 - Prognosis of mastectomy with reconstruction after neoadjuvant chemotherapy: a nationwide study in Korean Breast Cancer Society
Presenter: Sungmin Park
Session: Poster Display session 2
Resources:
Abstract
804 - A negative prognosis of radiotherapy-induced lower lymphocyte to monocyte ratio in patients with breast cancer
Presenter: Chang-ik Yoon
Session: Poster Display session 2
Resources:
Abstract
2701 - Patient data to monitor clinical patterns in early and advanced breast cancer in Europe
Presenter: Francesco Giusti
Session: Poster Display session 2
Resources:
Abstract
1437 - A critical appraisal of quality indicators of breast cancer treatment in Belgium
Presenter: Didier Verhoeven
Session: Poster Display session 2
Resources:
Abstract
1534 - Predictors of adherence among post-menopausal women receiving adjuvant endocrine therapy for breast cancer in Ontario, Canada
Presenter: Phillip Blanchette
Session: Poster Display session 2
Resources:
Abstract
4363 - Evaluation of endocrine therapy and patients preferences in early breast cancer: results of Elena study
Presenter: Emilia Montagna
Session: Poster Display session 2
Resources:
Abstract
2679 - Baseline Quality of life (QoL) and chemotherapy related toxicities (CRT) in localized breast cancer (BC) patients (pts): the French multicentric prospective CANTO cohort study
Presenter: Idlir Licaj
Session: Poster Display session 2
Resources:
Abstract