“Data are limited regarding the use of poly(adenosine diphosphate [ADP]–ribose) polymerase inhibitors, such as veliparib, in combination with chemotherapy followed by maintenance as initial treatment in patients with high-grade serous ovarian carcinoma,” the study authors observed.
This was an international, phase 3, placebo-controlled trial of patients with untreated stage 3 or 4 high-grade serous ovarian cancer. Patients were randomized 1:1:1 to one of the following groups: chemotherapy plus placebo followed by placebo maintenance (control), chemotherapy plus veliparib followed by placebo maintenance (veliparib combination only), or chemotherapy plus veliparib followed by veliparib maintenance (veliparib throughout). Patients could undergo cytoreductive surgery prior to initiation or after three cycles of trial treatment. The combination chemotherapy consisted of six cycles, and maintenance therapy was an additional 30 cycles. The main outcome measure was progression-free survival in the veliparib-throughout group compared to the control group, evaluated sequentially in the BRCA-mutation cohort, homologous-recombination deficiency (HRD) cohort (including the BRCA-mutation cohort), and intention-to-treat population.
Overall, 1,140 patients were randomized. Median progression-free survival in the BRCA-mutation cohort was 34.7 months in the veliparib-throughout group, compared to 22.0 months in the control group (hazard ratio [HR] for progression or death=0.44; 95% confidence interval [CI], 0.28-0.68; P<0.001). Progression-free survival in the HRD cohort was 31.9 months in the veliparib-throughout group versus 20.5 in the control group (HR=0.57; 95%CI, 0.43-0.76; P<0.001). In the intention-to-treat population, progression-free survival was 23.5 months in the veliparib-throughout group versus 17.3 months in the control group (HR=0.68; 95% CI, 0.56-0.83; P<0.001). Veliparib in combination with chemotherapy was associated with a higher incidence of anemia and thrombocytopenia, and a higher prevalence of nausea and fatigue.
The study results were published in The New England Journal of Medicine.
The study authors concluded, “Across all trial populations, a regimen of carboplatin, paclitaxel, and veliparib induction therapy followed by veliparib maintenance therapy led to significantly longer progression-free survival than carboplatin plus paclitaxel induction therapy alone. The independent value of adding veliparib during induction therapy without veliparib maintenance was less clear.”