Robert L. Coleman, MD
In the phase III VELIA/GOG-3005 trial—reported at the European Society for Medical Oncology (ESMO) Congress 20191 and simultaneously published in The New England Journal of Medicine2—Robert L. Coleman, MD, of The University of Texas MD Anderson Cancer Center, Houston, 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.
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–alone 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 six 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.
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–alone 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 the control group), 18.1 months in the homologous recombination–deficiency cohort (HR = 1.10, 95% CI = 0.86–1.41 vs the control group), and 15.2 months in the intention-to-treat population (HR = 1.07, 95% CI = 0.90–1.29 vs the control group). Overall survival data were immature at the time of analysis.
Grade 3 or 4 adverse events occurred in 88% in each of the two veliparib treatment groups and 77% of the control group.
The investigators concluded that “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.”
Disclosure: The study was funded by AbbVie. Dr. Coleman has served as a consultant or advisor to Clovis Oncology, Genentech/Roche, Esperance, AstraZeneca/MedImmune, Genmab, GamaMabsPharma, Tesaro, OncoMed, Sotio, Oncolytics, and AbbVie; has received reimbursement for travel, accommodations, and expenses from Merck, AstraZeneca/MedImmune, Array Biopharma, Clovis Oncology, Roche/Genentech, Research to Practice, GOG-Partners, Sotio, and Vaniam Group; and has received research funding from AstraZeneca/MedImmune, Esperance, OncoMed, Array, Clovis Oncology, Johnson & Johnson, Merck, Roche/Genentech, Abbott/AbbVie, and GOG Foundation. Dr. OMalley has received honoraria and/or institutional research support from AstraZeneca, Clovis, Tesaro, Immunogen, Janssen/J&J, AbbVie, Regeneron, Amgen, Novocure, Genentech/Roche, Eisai, Agenus, GSK, Merck, GOG Foundation, VentiRx, Array Biopharma, EMD Serono, Ergomed, Ajinomoto, Ludwig Cancer Research, Stemcentrx, Cerulean Pharma, Bristol Myers Squibb, Serono, Tracon Pharmaceuticals, Yale University, New Mexico Cancer Care Alliance, INC Research, inVentiv Health Clinical, Iovance Biotherapeutics, PRA International, Tarveda, Ambry, and Myriad Genetics.
1. Coleman RL, Fleming GF, Brady MF, et al: VELIA/GOG-3005. 2019 ESMO Congress. Abstract LBA3. Presented September 28, 2019.
2. Coleman RL, Fleming GF, Brady MF, et al: N Engl J Med 381:2403-2415, 2019.