Impact of homologous recombination status and responses with veliparib combined with first-line chemotherapy in ovarian cancer in the Phase 3 VELIA/GOG-3005 study

Elizabeth M. Swisher, Carol Aghajanian, David M. O'Malley, Gini F. Fleming, Scott H. Kaufmann, Douglas A. Levine, Michael J. Birrer, Kathleen N. Moore, Nick M. Spirtos, Mark S. Shahin, Thomas J. Reid, Michael Friedlander, Karina Dahl Steffensen, Aikou Okamoto, Vasudha Sehgal, Peter J. Ansell, Minh H. Dinh, Michael A. Bookman, Robert L. Coleman

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: In the Phase 3 VELIA trial (NCT02470585), PARP inhibitor (PARPi) veliparib was combined with first-line chemotherapy and continued as maintenance for patients with ovarian carcinoma enrolled regardless of chemotherapy response or biomarker status. Here, we report exploratory analyses of the impact of homologous recombination deficient (HRD) or proficient (HRP) status on progression-free survival (PFS) and objective response rates during chemotherapy. Methods: Women with Stage III-IV ovarian carcinoma were randomized to veliparib-throughout, veliparib-combination-only, or placebo. Stratification factors included timing of surgery and germline BRCA mutation status. HRD status was dichotomized at genomic instability score 33. During combination therapy, CA-125 levels were measured at baseline and each cycle; radiographic responses were assessed every 9 weeks. Results: Of 1140 patients randomized, 742 had BRCA wild type (BRCAwt) tumors (HRP, n = 373; HRD/BRCAwt, n = 329). PFS hazard ratios between veliparib-throughout versus control were similar in both BRCAwt populations (HRD/BRCAwt: 22.9 vs 19.8 months; hazard ratio 0.76; 95% confidence interval [CI] 0.53–1.09; HRP: 15.0 vs 11.5 months; hazard ratio 0.765; 95% CI 0.56–1.04). By Cycle 3, the proportion with ≥90% CA-125 reduction from baseline was higher in those receiving veliparib (pooled arms) versus control (34% vs 23%; P = 0.0004); particularly in BRCAwt and HRP subgroups. Complete response rates among patients with measurable disease after surgery were 24% with veliparib (pooled arms) and 18% with control. Conclusions: These results potentially broaden opportunities for PARPi utilization among patients who would not qualify for frontline PARPi maintenance based on other trials.

Original languageEnglish (US)
JournalGynecologic oncology
DOIs
StateAccepted/In press - 2021

Keywords

  • BRCA1/2
  • Homologous recombination deficiency
  • Veliparib

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynecology

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