Quality-adjusted progression-free survival analysis of veliparib and carboplatin/paclitaxel compared with chemotherapy alone in patients with newly diagnosed ovarian cancer (VELIA/GOG3005): ancillary analysis of a placebo-controlled, phase 3 randomized trial.

OBJECTIVE: Veliparib, a poly (adenosine diphosphate-ribose) polymerase inhibitor, was evaluated in a phase 3 trial (VELIA/GOG3005, NCT02470585) among patients with newly diagnosed stage III/IV high-grade serous ovarian cancer. The addition of veliparib to carboplatin and paclitaxel chemotherapy, followed by veliparib maintenance, compared with chemotherapy with placebo, followed by placebo maintenance demonstrated improved progression-free survival. This analysis evaluated quality-adjusted progression-free survival and quality-adjusted time without symptoms of disease or toxicity. METHODS: Patient-centered outcomes were assessed in 344 veliparib and 351 placebo subjects, including homologous recombination-deficient and BRCA-deficient sub-groups. Progression-free survival was partitioned into time with and without toxicity. Clinically meaningful treatment emergent adverse events included nausea, vomiting, and fatigue. Quality-adjusted progression-free survival assessed the duration of good quality of life, incorporating progression-free survival and health states. Quality-adjusted time without symptoms of disease or toxicity was calculated as utility-weighted sums of mean health state durations. Sensitivity analyses were conducted using ≥ grade 2 or 3 adverse events. RESULTS: A significant difference in mean quality-adjusted progression-free survival was seen in favor of chemotherapy with veliparib compared with chemotherapy with placebo (19.5 months vs 16.5 months, 95% confidence interval 1.42 to 4.61, p < .0001). The mean quality-adjusted time without symptoms of disease or toxicity was longer for patients in the chemotherapy with veliparib arm than in the chemotherapy with placebo arm (20.82 months vs 18.06 months, 95% confidence interval 1.09 to 4.47, p < .001). Similar differences in mean quality-adjusted time without symptoms of disease or toxicity were observed for the homologous recombination-deficient (p < .001) and BRCA mutation (p < .001) sub-group analyses. CONCLUSIONS: Compared with chemotherapy with placebo, veliparib added to chemotherapy and continued as maintenance had significant patient-centered benefits in terms of quality-adjusted progression-free survival and on-treatment quality-adjusted time without symptoms of disease or toxicity for the overall, homologous recombination-deficient, and BRCA mutation patient populations.

Duke Scholars

Author Angeles Alvarez Secord Obstetrics and Gynecology, Gynecologic Oncology