Abstract 325P
Background
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 (hazard ratio=0.71 [95% CI: 0.57, 0.88], P=0.002; NCT02163694 [BROCADE3]). In a subgroup of pts treated with Vel+C-P, response was durable with PFS of >24 months (mo). We describe the characteristics and response of this subgroup of pts.
Methods
Pts with gBRCA1/2 mutations and ≤2 prior lines of cytotoxic therapy for metastatic breast cancer were randomized 2:1 to Vel (120 mg PO BID) + C-P or placebo (Pbo) + C-P. Vel or Pbo was given on days (d) −2 to 5 with C (AUC 6, d1) and weekly P (80 mg/m2, d1, 8, 15) in 21-d cycles. Pts who discontinued C and P but did not progress continued to receive blinded single-agent Vel or Pbo (300–400 mg BID) until progression. Primary endpoint was investigator-assessed PFS.
Results
In total, 81 of 337 pts (24%) in the intent-to-treat (ITT) population who received Vel+C-P had a durable (>24 mo) response vs. 23 (13%) in the Pbo+C-P arm. Median age of Vel+C-P durable responders was 49 (range 25–78), most were female (80 [98.8%]) and Caucasian (70 [86.4%]), mirroring demographics in the ITT Vel+C-P arm. Baseline disease characteristics of Vel+C-P and Pbo+C-P durable responders vs. ITT Vel+C-P are shown in the table and show no relevant differences. Median PFS (mo; 95% CI)/48-mo PFS estimates (%; 95% CI) for Vel+C-P and Pbo+C-P durable responders, respectively: not reached (NR) (46.3–NR)/54.7% (20.0–79.7) and 38.7 mo (27.2–49.7)/30.4% (9.5–54.8), and for ITT Vel+C-P: 14.5 mo (12.5–17.7)/18.3% (8.8–30.7).
Conclusions
Baseline and disease characteristics of pts treated with Vel+C-P who had durable responses were generally similar to pts in the ITT population, with no identifiable characteristic predictive of longer response. Table: 325P
| Characteristic, n (%) | Pbo+C-PDurable RespondersN=23 | Vel+C-PDurable RespondersN=81 | Vel+C-PITTN=337 |
| Age, years median [range] | 47 [28–61] | 49 [25–78] | 47 [24–82] |
| Hormone Receptor Expression | |||
| Estrogen and/or Progesterone Receptor positive | 10 (44) | 37 (46) | 174 (52) |
| BRCA Mutation Status | |||
| BRCA1/BRCA2 | 13 (57)/10 (44) | 46 (57)/38 (47) | 177 (53)/167 (50) |
| Eastern Cooperative Oncology Group performance status | |||
| 0 | 17 (74) | 61 (75) | 208 (62) |
| 1–2 | 6 (26) | 20 (25) | 129 (38) |
| Metastases | |||
| Liver | 5 (22) | 28 (35) | 132 (39) |
| Lung | 10 (44) | 32 (40) | 138 (41) |
| CNS | 2 (9) | 3 (4) | 12 (4) |
| Prior platinum | 2 (9) | 6 (7) | 27 (8) |
| Prior (neo)adjuvant chemotherapy | 16 (70) | 55 (68) | 236 (70) |
| Prior chemotherapy for metastatic disease | 2 (9) | 10 (12) | 63 (19) |
Clinical trial identification
NCT02163694.
Editorial acknowledgement
Medical writing support was provided by Joanne Franklin, PhD, CMPP, from Aptitude Health, The Hague, the Netherlands, and funded by AbbVie.
Legal entity responsible for the study
AbbVie Inc.
Funding
AbbVie Inc.
Disclosure
B. Kaufman: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Steering Committee: AbbVie; Advisory/Consultancy, Speaker Bureau/Expert testimony: Roche; Advisory/Consultancy: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony: Lilly; Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer; Advisory/Consultancy: Tesaro; Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca. H. 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. B. Arun: Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Pharmamar; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Invitae; Advisory/Consultancy, Steering Committee (non-paid): AbbVie. H. Wildiers: Honoraria (institution): AstraZeneca; Honoraria (institution): Biocartis; Honoraria (institution): Lilly; Honoraria (institution), Research grant/Funding (institution): Novartis; Honoraria (institution), Travel/Accommodation/Expenses: Pfizer; Honoraria (institution): PUMA Biotechnology; Honoraria (institution), Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Honoraria (institution): Sirtex; Honoraria (institution): Daiiji. M. Friedlander: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Honoraria (self), Advisory/Consultancy, Non-remunerated activity/ies, Steering Committee: MSD; Advisory/Consultancy, Non-remunerated activity/ies, Steering Committee (non-rem): AbbVie; Honoraria (self), Advisory/Consultancy: Lilly; Honoraria (self), Advisory/Consultancy: Takeda; Honoraria (self), Advisory/Consultancy: Novartis; Research grant/Funding (institution): BeiGene. 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. 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. D. Maag: Shareholder/Stockholder/Stock options, Full/Part-time employment: AbbVie. D. Feng: Shareholder/Stockholder/Stock options, Full/Part-time employment: AbbVie. S. Fages: Shareholder/Stockholder/Stock options, Full/Part-time employment: AbbVie. 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; Advisory/Consultancy: Sankyo; Advisory/Consultancy: Seattle Genetics; Advisory/Consultancy: AstraZeneca.