In the phase III VELIA/GOG-3005 trial—reported at the European Society for Medical Oncology (ESMO) Congress 2019 (Abstract LBA3) and simultaneously published in The New England Journal of Medicine—Robert L. Coleman, MD, and colleagues found that the use of the poly (ADP-ribose) polymerase inhibitor veliparib with first-line induction chemotherapy and as maintenance therapy was associated with improved progression-free survival in patients with stage III or IV high-grade serous ovarian carcinoma vs induction chemotherapy alone.

Robert L. Coleman, MD

Study Details

The double-blind trial included 1,140 patients from 210 sites in 10 countries. They were randomly assigned 1:1:1 between July 2015 and July 2017 to receive first-line induction chemotherapy with carboplatin/paclitaxel plus placebo followed by placebo maintenance (control group, n = 375); chemotherapy plus veliparib followed by placebo maintenance (veliparib combination–only group, n = 383); or chemotherapy plus veliparib followed by veliparib maintenance (veliparib-throughout group, n = 382). Cytoreductive surgery could be performed prior to initiation of or after three cycles of trial treatment.

Combination chemotherapy was given for 6 cycles, and maintenance therapy was given for 30 cycles. The veliparib dose was 150 mg twice daily during combination therapy and 300 mg twice daily during the first 2 weeks of maintenance therapy, followed by 400 mg twice daily.

The primary endpoint was investigator-assessed progression-free survival in the veliparib-throughout group vs the control group, analyzed sequentially in the BRCA mutation cohort (26% of population), the homologous recombination deficiency cohort (which included the BRCA mutation cohort, 55% of patients), and the intention-to-treat population.

Progression-Free Survival

Median follow-up was 28 months. For the veliparib-throughout group vs the control group, median progression-free survival was 34.7 months vs 22.0 months in the BRCA mutation cohort (hazard ratio [HR] =  0.44; P < .001), 31.9 months vs 20.5 months in the homologous recombination deficiency cohort (HR = 0.57; P < .001), and 23.5 months vs 17.3 months in the intention-to-treat population (HR = 0.68; P < .001).

In the veliparib combination–only group, median progression-free survival was 21.1 months in the  BRCA mutation cohort (HR = 1.22, 95% confidence interval [CI] = 0.82–1.80 vs control group), 18.1 months in the homologous recombination deficiency cohort (HR = 1.10, 95% CI = 0.86–1.41 vs control), and 15.2 months in the intention-to-treat population (HR = 1.07, 95% CI = 0.90–1.29 vs control). Overall survival data were immature at the time of analysis.

Adverse Events

Grade 3 or 4 adverse events occurred in 88% of each of the two veliparib treatment groups and 77% of the control group. The veliparib-throughout group had higher rates of grade 3 or 4 anemia (38% vs 26%) and thrombocytopenia (28% vs 8%) among hematologic adverse events, and nausea (8% vs 3%) and fatigue (8% vs 3%) among nonhematologic adverse events compared with the control group.

One patient in the veliparib combination–only group developed myelodysplastic syndrome, and one in the veliparib-throughout group developed acute myeloid leukemia. During maintenance therapy, 19% of patients in the veliparib-throughout group and 6% in the control group discontinued treatment due to adverse events, with the most common cause in the veliparib-throughout group being nausea (8%).

The investigators 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.”

Disclosure: The study was funded by AbbVie. For full disclosures of the study authors, visit nejm.org.