Found 1 Presentation For Request ""140O - Veliparib plus carboplatin-paclitaxel""
140O - Veliparib plus carboplatin-paclitaxel in patients with HER2-negative advanced/metastatic gBRCA-associated breast cancer: Results in hormone receptor-positive and triple-negative breast cancer subgroups from the phase III BROCADE3 trial
- Jean-Pierre Ayoub (Montreal, Canada)
- Michael L. Friedlander (Randwick, Australia)
- Veronique C. Dieras (Rennes, France)
- Hans Wildiers (Leuven, Belgium)
- Banu Arun (Houston, TX, United States of America)
- Hyo S. Han (Tampa, United States of America)
- Shannon Puhalla (Pittsburgh, United States of America)
- Yaroslav Shparyk (Lviv, Ukraine)
- Erik H. Jakobsen (Vejle, Denmark)
- Madan G. Kundu (North Chicago, United States of America)
- Meijing Wu (North Chicago, United States of America)
- Christine Ratajczak (North Chicago, United States of America)
- David Maag (North Chicago, United States of America)
- Bella Kaufman (Tel Aviv-Yafo, Israel)
Abstract
Background
In BROCADE3 (NCT02163694), addition of the PARP1/2 inhibitor veliparib (Vel) to carboplatin-paclitaxel (C-P) significantly prolonged progression-free survival (PFS) in patients (pts) with HER2-negative locally advanced/metastatic gBRCA-associated breast cancer (BC; hazard ratio=0.71 [95% CI 0.57, 0.88], P=.002). Here we report efficacy and safety in hormone receptor-positive (HR+) and triple-negative BC (TNBC) subgroups separately.
Methods
Pts with ≤2 prior lines of cytotoxic therapy for metastatic BC were randomized 2:1 to Vel (120 mg PO BID) + C-P or placebo (Pbo) + C-P. Vel-Pbo was given on days (d) –2 to 5, C (AUC 6 mg/mL/min IV) on d 1, and P (80 mg/m2 IV) on d 1, 8, and 15 (21-d cycles). Pts who discontinued C and P prior to progression (at investigator discretion) received blinded single-agent Vel or Pbo (300–400 mg BID) until progression. Primary endpoint was investigator-assessed PFS. Analysis of PFS in subgroups defined by hormone receptor status was preplanned. Analyses of PFS and overall survival (OS) were stratified by prior platinum status.
Results
Among the 509 pts in the intent-to-treat population, 266 (52%) were HR+ and 243 (48%) had TNBC. PFS and OS results in each subgroup are presented in the table below. Adverse events (not related to progression) led to study drug discontinuation in 8.0%/3.3% of HR+ pts and 10.5%/7.5% of TNBC pts in the Vel + C-P and Pbo + C-P arms, respectively. On the basis of stratified log-rank test. P values are nominal. BICR, blinded independent central review; C-P, carboplatin plus paclitaxel; ER, estrogen receptor; HR+, hormone receptor positive (ER and/or PgR); INV, investigator; m, median; NR, not reached; OS, overall survival; PFS, progression-free survival; PgR, progesterone receptor; TNBC, triple-negative breast cancer.
HR+ Subgroup TNBC Subgroup Veliparib + C-P n=174 Placebo + C-P n=92 Veliparib + C-P n=163 Placebo + C-P n=80 mPFS per INV, mo (95% CI) 13.0 (12.1, 16.6) 12.5 (10.2, 13.2) 16.6 (12.3, 22.7) 14.1 (11.0, 15.8) PFS hazard ratio (95% CI) 0.69 (0.52, 0.93) 0.72 (0.52, 1.00) PFS rate at 2 years, % (95% CI) 27.5 (20.6, 34.8) 15.3 (8.2, 24.5) 40.4 (32.3, 48.4) 25.0 (15.3, 35.9) PFS rate at 3 years, % (95% CI) 17.5 (11.2, 25.0) 8.6 (3.3, 17.0) 35.3 (27.2, 43.6) 13.0 (5.3, 24.2) mPFS per BICR, mo (95% CI) 18.7 (14.5, 22.9) 12.6 (11.4, 16.5) 21.0 (16.0, 29.3) 14.5 (12.5, 19.7) PFS hazard ratio (95% CI) 0.68 (0.48, 0.97) 0.71 (0.49, 1.03) PFS rate at 2 years, % (95% CI) 39.5 (30.6, 48.2) 25.5 (13.9, 39.0) 47.4 (38.3, 56.0) 29.0 (17.7, 41.3) PFS rate at 3 years, % (95% CI) 35.1 (26.0, 44.3) 18.6 (8.1, 32.4) 39.7 (30.2, 48.9) 20.9 (9.5, 35.3) mOS (mo, 95% CI) [interim] 32.4 (26.5, 37.9) 27.1 (22.9, 35.2) 35.0 (24.9, NR) 30.0 (24.5, NR) OS hazard ratio (95% CI) 0.96 (0.68, 1.36) 0.92 (0.62, 1.36)
Conclusions
The addition of Vel to C-P improved PFS in gBRCA pts with HR+ BC and TNBC. In both subgroups, benefit of Vel was durable with an increase in proportion of pts progression free at 2 and 3 years compared with Pbo.
Clinical trial identification
NCT02163694.
Editorial acknowledgement
Medical writing support was provided by Mary L. Smith, PhD, CMPP, from Aptitude Health, Atlanta, GA, and funded by AbbVie.
Legal entity responsible for the study
AbbVie Inc.
Funding
AbbVie Inc.
Disclosure
J-P. Ayoub: Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Boston Biomedical; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Eisai; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer; Advisory/Consultancy: Puma; Advisory/Consultancy: Roche. M.L. Friedlander: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy, Inc. Steering Committee: MSD; Advisory/Consultancy, Non-remunerated activity/ies: AbbVie; Honoraria (self), Advisory/Consultancy: Lilly; Honoraria (self), Advisory/Consultancy: Takeda; Honoraria (self), Advisory/Consultancy: Novartis; Research grant/Funding (self): BeiGene. V.C. Dieras: Advisory/Consultancy: Roche/Genentech; Advisory/Consultancy: Novartis; Advisory/Consultancy: Lilly; Advisory/Consultancy: Pfizer; Advisory/Consultancy: AbbVie; Advisory/Consultancy: MSD; Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy: Seattle Genetics; Advisory/Consultancy: AstraZeneca. H. Wildiers: Honoraria (institution): Roche/Genentech; Honoraria (institution): AstraZeneca; Honoraria (institution): Amgen; Honoraria (institution): Lilly; Honoraria (institution): Novartis; Honoraria (institution): AbbVie; Honoraria (institution): Vifor Pharma; Honoraria (institution), Travel/Accommodation/Expenses: Pfizer; Honoraria (institution): Celldex Therapeutics; Honoraria (institution): Janssen-Cilag; Honoraria (institution): TRM Oncology; Honoraria (institution): PUMA Biotechnology; Honoraria (institution): Orion Corporation; Research grant/Funding (institution): Roche; Travel/Accommodation/Expenses: Roche. B. Arun: Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): PharmaMar; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Invitae; Non-remunerated activity/ies: AbbVie. H.S. Han: Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Prescient; Research grant/Funding (institution): Horizon; Research grant/Funding (institution): Karyopharm; Research grant/Funding (institution): BMS; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Tesaro; Research grant/Funding (institution): TapImmune; Research grant/Funding (institution): Seattle Genetics; Research grant/Funding (institution), Grant: Department of Defense; Speaker Bureau/Expert testimony: Lilly. S. Puhalla: Advisory/Consultancy, Research grant/Funding (institution): AbbVie; Advisory/Consultancy: MedImmune; Advisory/Consultancy: Celldex; Advisory/Consultancy: Puma; Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Advisory/Consultancy: Eisai; Advisory/Consultancy: NanoString; Research grant/Funding (institution): Lilly; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Incyte; Research grant/Funding (institution): Covance-Bayer; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): Medivation. Y. Shparyk: Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self): Roche; Honoraria (self): AstraZeneca; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Roche; Research grant/Funding (institution): MSD; Research grant/Funding (institution): Boehringer Ingelheim. E.H. Jakobsen: Advisory/Consultancy: Pfizer; Advisory/Consultancy: Novartis; Advisory/Consultancy: Roche; Advisory/Consultancy: Lilly; Advisory/Consultancy: Puma; Non-remunerated activity/ies, principal investigator BROCADE3 trial: AbbVie. M.G. Kundu: Shareholder/Stockholder/Stock options, Full/Part-time employment: AbbVie. M. Wu: Shareholder/Stockholder/Stock options, Full/Part-time employment: AbbVie. C. Ratajczak: Shareholder/Stockholder/Stock options, Full/Part-time employment: AbbVie. D. Maag: Shareholder/Stockholder/Stock options, Full/Part-time employment: AbbVie. B. Kaufman: Advisory/Consultancy: Roche; Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Lilly; Honoraria (self), Advisory/Consultancy: Pfizer; Advisory/Consultancy: AbbVie; Advisory/Consultancy: Tesaro; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self): Roche; Honoraria (self), Steering committee: AbbVie.