...evaluating veliparib in combination with carboplatin/paclitaxel with continuation as monotherapy if carboplatin/paclitaxel is discontinued in patients with germline BRCA1/2 mutation-associated, advanced HER2-negative breast cancer...CPH model indicated a flat exposure-response relationship between the veliparib exposure and PFS when veliparib was administered in combination with carboplatin/paclitaxel or as monotherapy....These analyses support the dose regimen of veliparib (120 mg twice daily) in combination with carboplatin/paclitaxel...

Median PFS was longer in the veliparib arm compared with the placebo arm for all subgroups...gBRCA1: 14.2 vs 12.6 months, hazard ratio (95% CI): 0.75 (0.55, 1.03), p = 0.073; gBRCA2: 14.6 vs 12.6 months, hazard ratio (95% CI): 0.69 (0.50, 0.95); p = 0.021)....Veliparib plus carboplatin/paclitaxel resulted in durable benefit in subgroups defined by HR status or by gBRCA1 versus gBRCA2 mutation.

...in patients with germline BRCA-associated locally advanced/metastatic HER2- breast cancer...Patients were randomised 2:1 to receive veliparib (120 mg orally BID) or placebo on days -2 to 5. Carboplatin (AUC 6) was administered on day 1, and paclitaxel (80 mg/m2) on days 1, 8 and 15 (21-day cycles). In the first-line subgroup, median PFS was 16.6 months (95% confidence interval [CI] 13.4-18.7) versus 13.1 months (95% CI 11.4-14.5) for the veliparib versus control groups (hazard ratio 0.70, 95% CI 0.54-0.89, P = .004). More patients were alive and progression-free at 2 years (36% versus 23.2%) and 3 years (27.9% versus 13.3%) in the veliparib versus control group. Veliparib with carboplatin-paclitaxel led to durable disease control among first-line patients, suggesting a benefit of this treatment approach in early lines.

...metastatic or locally advanced unresectable HER2-negative breast cancer and deleterious or suspected deleterious gBRCA1 or gBRCA2 mutations...patients had received ≥1 dose of open-label crossover veliparib monotherapy after progression...within each subgroup, there were patients who were progression free for 12 months or longer (BRCA1, 2 patients; BRCA2, 3 patients; TNBC, 3 patients; hormone receptor positive, 2 patients...

The proportion of as-treated pts with BRCA1 or BRCA2 mutations was comparable between the Vel + C/P (51.4% BRCA1, 48.6% BRCA2) and Pbo + C/P (50.9% BRCA1, 49.1% BRCA2) study arms...Investigator-assessed PFS for the Vel + C/P and Pbo + C/P arms was 14.2 mo vs 12.6 mo, respectively, in the BRCA1 subgroup (HR=0.75 [95% CI: 0.55, 1.03]; P=0.073) and 14.6 mo vs 12.6 mo, respectively, in the BRCA2 subgroup (HR=0.69 [95% CI: 0.50, 0.95]; P=0.021)...

...patients were assigned to receive veliparib plus carboplatin-paclitaxel (veliparib group) and 172 were assigned to receive placebo plus carboplatin-paclitaxel (control group). Median follow-up at data cutoff (April 5, 2019) was 35·7 months (IQR 24·9-43·6) in the veliparib group and 35·5 months (23·1-45·9) in the control group....resulted in significant and durable improvement in progression-free survival in patients with germline BRCA mutation-associated advanced breast cancer.

...BROCADE 3 clinical trial examining carboplatin and paclitaxel with the addition of veliparib or placebo...longest progression-free and overall survival to date with PARP inhibitor therapy in advanced germline BRCA1 and BRCA2 mutation-associated breast cancer.

...- Phase I: Patients must have received at least one prior chemotherapy regimen for metastatic disease; patients with deleterious germ line mutations in breast cancer (BRCA)1 or BRCA2 are...

...- Have a documented BRCA1/2 mutation and a BRCA related malignancy (primarily breast or ovarian cancers, but also may include prostate or pancreatic cancers);...

...- HER negative with a known germline BRCA1/2 mutation...

...- Confirmed BRCA1 or BRCA2 mutation associated breast cancer...