Veliparib-chemo combo prolongs survival without disease progression in some advanced breast cancer patients

The double blind, placebo-controlled, phase 3 BROCADE 3 trial showed that veliparib in combination with chemotherapy significantly prolongs progression-free survival (PFS) in women with metastatic HER2-negative breast cancer with BRCA mutations, compared with women on chemotherapy alone. Results were presented by Veronique Diéras (Centre Eugène Marquis, Rennes, France) [1].

The rationale behind the trial rose from the fact that BRCA-mutated tumours are deficient in homologous recombination that occurs during DNA repair, making them susceptible to both platinum and PARP inhibitors, such as veliparib. Patients were randomised 2:1 to receive oral veliparib at 120 mg twice daily or placebo on days 2 to 5, administered with carboplatin AUC 6 on day 1 and weekly paclitaxel at 80 mg/m² on days 1, 8, and 15 in 21-day cycles. Patients discontinuing both carboplatin and paclitaxel without disease progression received blinded single agent veliparib at 300 to 400 mg twice daily or placebo. All patients had germline BRCA1/2 mutations and had previously received ≤2 lines of cytotoxic therapy for metastatic breast cancer. Investigator-assessed PFS served as the primary endpoint and secondary endpoints included overall survival (OS), clinical benefit rate (CBR), objective response rate (ORR), and PFS2.

Median PFS per investigator in 337 patients treated with veliparib plus chemotherapy was 14.5 months (95% CI 12.5–17.7) compared with 12.6 months (95% CI 10.6-14.4) in 172 patients receiving placebo plus chemotherapy (HR 0.71; 95% CI 0.57-0.88; P=0.002: see Figure). Duration of response was longer at 19.3 (95% CI 16.5- 23.3) months compared with 13.5 (95% CI 12.5-16.3) months, respectively (HR 0.70; 95% CI 0.54-0.90). PFS at 3 years was doubled with veliparib; the respective cohorts demonstrated 3-year PFS rates of 26% vs 11%.

Figure. BROCADE3 primary endpoint: PFS by Investigator Assessment.



© Véronique Diéras (provided by ESMO).

Median OS at 24 weeks was unchanged; 33.5 (95% CI 27.6-37.9) months with veliparib/chemotherapy compared with 28.2 (95% CI 24.7-35.2) months with placebo/chemotherapy (HR 0.95; 95% CI 0.73-1.2; P=0.67). Likewise, CBR (90.7% vs 93.2%) and ORR (75.8% vs 74.1%) were similar between arms. However, prolonged PFS2 was seen with veliparib (21.3 months; 95% CI 19.8-25.1) vs placebo (17.4 months; 95% CI 16.0-20.0) HR 0.76

Importantly, the addition of veliparib did not substantially alter the toxicity profile of chemotherapy. The most common ≥grade 3 adverse event occurring ≥20% of patients in the respective arms were anaemia (27% vs 17%), neutropenia (52% vs 50%), and thrombocytopenia (25% vs 15%).

1. Diéras VC et al. ESMO Congress 2019. Abstract LBA9.

Posted on 26 November 201929 February 2024