Veliparib in combination with chemotherapy significantly prolongs survival without disease progression in women with metastatic HER2-negative breast cancer with BRCA mutations, compared with women on chemotherapy alone, a Phase 3 trial shows.
The trial’s findings were presented in a session, titled “Phase 3 study of veliparib with carboplatin and paclitaxel in HER2-negative advanced/metastatic gBRCA-associated breast cancer,” at the recent European Society for Medical Oncology (ESMO) 2019 Congress, in Barcelona.
It is a PARP inhibitor that works by blocking the activity of PARP enzymes, which are involved in DNA repair. By blocking the activity of these enzymes, veliparib prevents cancer cells from repairing their DNA, thereby eventually eliminating them.
The AbbVie-funded, double-blind, placebo-controlled BROCADE3 Phase 3 trial (NCT02163694) is currently investigating the effects of veliparib in combination with platinum-based chemotherapy in women with locally advanced or metastatic HER2-negative breast cancer with BRCA mutations.
About 500 women enrolled in the trial were randomly assigned to receive either oral veliparib in combination with chemotherapy (carboplatin and paclitaxel), or a placebo in combination with chemotherapy, in cycles of 21 days, until disease progression or unacceptable toxicity.
The trial’s primary endpoint was to assess the time patients lived until disease progression or death, whichever occurred first. Secondary endpoints included overall survival, the percentage of patients responding to treatment, and duration of response.
The trial met its primary endpoint, with veliparib extending the time women lived without showing signs of disease progression from a median of 12.6 to 14.5 months, according to the new findings presented at the conference by Véronique Diéras, MD, from France’s Institut Curie and Centre Eugène Marquis. With veliparib, the risk of disease progression or death from any cause was cut by 29%.
Results also suggested some survival benefit of veliparib over placebo — overall survival was 33.5 months versus 28.2 months — but this difference did not reach statistical significance.
While not tested for significance, the findings showed that veliparib increased the median duration of response from 11.0 to 14.7 months. However, the percentage of women responding to treatment was similar in both groups (75.8% for those receiving veliparib and 74.1% for those receiving chemotherapy alone).
Safety analyses indicated the addition of veliparib to chemotherapy did not have a dramatic impact in treatment toxicity. The most common treatment-related severe adverse events reported in the trial included anemia, low white blood cell counts (neutropenia), and low platelet counts (thrombocytopenia).
More than half of the patients in the two treatment groups required dose adjustments of both chemotherapy agents.
“The investigators concluded that these findings demonstrated a significant improvement in [the time patients lived until disease progression or death] with veliparib, carboplatin and paclitaxel over placebo, carboplatin and paclitaxel,” according to an ESMO news release.
In another clinical trial presented at the ESMO conference, a similar combination of veliparib and chemotherapy also extended the time without disease progression or death in women with advanced forms of ovarian cancer, supporting the broad application of this combination.