2017 ASCO Annual Meeting!
Session: Breast Cancer—Metastatic
Type: Oral Abstract Session
Time: Saturday June 3, 1:15 PM to 4:15 PM
Location: Hall D1
Final results of a phase 2 study of talazoparib (TALA) following platinum or multiple cytotoxic regimens in advanced breast cancer patients (pts) with germline BRCA1/2 mutations (ABRAZO).
2017 ASCO Annual Meeting
J Clin Oncol 35, 2017 (suppl; abstr 1007)
Author(s): Nicholas C. Turner, Melinda L. Telli, Hope S. Rugo, Audrey Mailliez, Johannes Ettl, Eva-Maria Grischke, Lida A. Mina, Judith Balmana Gelpi, Peter A. Fasching, Sara A. Hurvitz, Andrew M. Wardley, Colombe Chappey, Wendy Verret, Alison L. Hannah, Mark E. Robson; Royal Marsden Hospital, The Institute of Cancer Research, London, United Kingdom; Stanford University Medical Center, Stanford, CA; University of California San Francisco Comprehensive Cancer Center, San Francisco, CA; Centre Oscar Lambret, Lille, France; Klinikum Rechts der Isar, Technische Universität München, Munich, Germany; Universitӓts-Frauenklinik Tubingen, Eberhard Karls University, Tubingen, Germany; Banner Health, Phoenix, AZ; Hospital Vall d’Hebron, Barcelona, Spain; University of Erlangen, Erlangen, Germany; University of California Los Angeles Health, Santa Monica, CA; The Christie Hospital, Huddersfield, United Kingdom; Medivation, Inc., San Francisco, CA; Memorial Sloan-Kettering Cancer Center, New York, NY
Background: TALA is a dual-mechanism PARP inhibitor that traps PARP on DNA. This study was designed to assess the activity of TALA in pts with gBRCA1/2mutation previously exposed to platinum or multiple prior cytotoxic regimens. Methods: ABRAZO (NCT02034916) is a 2-cohort, 2-stage phase 2 study of TALA (1 mg/d) following platinum-based therapy (Cohort 1 [C1]) or ≥ 3 platinum-free cytotoxic-based regimens (Cohort 2 [C2]) in pts with locally advanced or metastatic breast cancer (MBC) and gBRCA1/2mutation. Pts had ECOG PS ≤ 1 and measurable disease by RECIST v1.1. Five responses per cohort were required in ≤ 35 pts to progress to stage 2. The primary endpoint was confirmed ORR by independent radiology facility (IRF). Secondary endpoints: clinical benefit rate ≥ 24 weeks (CBR24), DOR, PFS, and OS. Results: From May 2014 to Feb 2016, 84 pts were enrolled (C1, n = 49; C2, n = 35). At data cutoff (1 Sep 2016), 9 pts continued on treatment. Both cohorts proceeded to stage 2 before enrollment closed. Median age was 50 (range, 31–75) years; 58% of pts had an ECOG PS of 0. TNBC/HR+ incidence in C1 and C2 was 59%/41% and 17%/83%, respectively. Median number of prior cytotoxic regimens administered for advanced disease was 2 in C1 and 4 in C2. ORR by IRF for BRCA1/BRCA2 was 24%/34%, and ORR by IRF for TNBC/HR+ was 26%/29%. Common all grade AEs: anemia (52%), fatigue (45%), nausea (42%), diarrhea (33%), thrombocytopenia (33%), and neutropenia (27%). Grade ≥ 3 AEs: anemia (35%), thrombocytopenia (19%), and neutropenia (15%). Nonhematological AEs grade ≥ 3 did not occur. AEs related to TALA led to drug discontinuation in 3 pts (4%); 4 AEs resulted in death, none related to TALA. Conclusions: TALA was well tolerated in MBC pts with a gBRCA1/2 mutation, exhibiting promising antitumor activity in C1 and C2. TALA vs physician’s choice of treatment in gBRCA1/2-mutated MBC is being evaluated in the phase 3 EMBRACA trial (NCT01945775). Clinical trial information: NCT02034916
|C1 (n = 48)||C2 (n = 35)|
|ORR by IRF, n (% [95% CI])||10 (21% [10, 35])||13 (37% [21, 55])|
|DOR by IRF, mo (95% CI)||5.8 (2.8, not reached)||3.8 (2.8, 10.1)|
|CBR24 by INV, n (% [95% CI])||18 (38% [24, 53])||23 (66% [48, 81])|
|PFS by INV, mo (95% CI)||4.0 (2.8, 5.4)||5.6 (5.5, 7.8)|