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Poster Display session 2

2575 - Next-generation DNA Sequencing (NGS) Results for Tumors From Phase 2 ABRAZO Study of Talazoparib After Platinum or Cytotoxic Non-Platinum Regimens in Patients (pts) With Advanced Breast Cancer (ABC) and Germline BRCA1/2 (gBRCA) Mutations

Date

29 Sep 2019

Session

Poster Display session 2

Topics

Tumour Site

Breast Cancer

Presenters

Nicholas C. Turner

Citation

Annals of Oncology (2019) 30 (suppl_5): v104-v142. 10.1093/annonc/mdz242

Authors

N.C. Turner1, A..D. Laird2, M.L. Telli3, H.S. Rugo4, A. Mailliez5, J. Ettl6, E. Grischke7, L.A. Mina8, J. Balmaña9, P.A. Fasching10, S.A. Hurvitz11, L.A. Albacker12, G.M. Frampton12, J. Chelliserry13, P. Bycott14, U. Conte15, A.M. Wardley16, M.E. Robson17

Author affiliations

  • 1 Molecular Oncology, Royal Marsden Hospital, The Institute of Cancer Research, SW73RP - London/GB
  • 2 Early Development, Translational And Immuno-oncology (edto), Pfizer Oncology, San Francisco/US
  • 3 School Of Medicine, Stanford University, San Francisco/US
  • 4 Medicine, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco/US
  • 5 Oncological Cancer, Centre Oscar Lambret, Lille/FR
  • 6 Obstetrics And Gynecology, Technical University of Munich, School of Medicine, Klinikum rechts der Isar, Munich/DE
  • 7 Dept. Für Frauengesundheit, Universitӓts Frauenklinik Tubingen, Eberhard Karls University, 72072 - Tübingen/DE
  • 8 Medical Oncology, Banner MD Anderson Cancer Center, Gilbert/US
  • 9 Medical Oncology, Hospital Vall d’Hebron, and Vall d’Hebron Institute of Oncology, Universitat Autònoma de Barcelona, Barcelona/ES
  • 10 Gynecology And Obstetrics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen/DE
  • 11 Medicine, University of California Los Angeles, Los Angeles/US
  • 12 Cancer Genomics, Foundation Medicine Inc., Cambridge/US
  • 13 Molecular Diagnostics, Pfizer Inc., San Diego/US
  • 14 Statistics, Pfizer Inc., San Diego/US
  • 15 Clinical Research & Development, Pfizer Inc., New York/US
  • 16 Medical Oncology, The NIHR Manchester Cancer Research UK Clinical Research Facility at The Christie NHS Foundation Trust & Division of Cancer Sciences University of Manchester, Manchester/GB
  • 17 Medical Oncology, Memorial Sloan Kettering Cancer Center, New York/US

Resources

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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.

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