Progression-free survival by investigator versus blinded independent central review in newly diagnosed patients with high-grade serous ovarian cancer: Analysis of the VELIA/GOG-3005 trial

Gynecol Oncol. 2021 Aug;162(2):375-381. doi: 10.1016/j.ygyno.2021.05.031. Epub 2021 Jun 8.

Abstract

Objective: In the phase 3 VELIA/GOG-3005 trial, veliparib added to carboplatin-paclitaxel and continued as maintenance improved progression-free survival (PFS) compared to carboplatin-paclitaxel alone in patients with newly diagnosed ovarian carcinoma. Primary analysis of PFS was by investigator (INV) assessment, with a supplemental analysis of PFS by blinded independent central review (BICR).

Methods: Patients received veliparib or placebo with carboplatin-paclitaxel (6 cycles) and as maintenance (30 additional cycles). The primary analysis compared PFS in the veliparib-throughout arm to the carboplatin-paclitaxel only arm in the BRCA mutation (BRCAm), homologous recombination deficiency (HRD), and intention-to-treat (ITT) populations. Exploratory analyses of PFS in BRCA wildtype (BRCAwt), homologous recombination proficient (HRP), and HRD + BRCAwt populations were also performed. PFS per BICR and overall concordance rates between INV and BICR assessments were analyzed.

Results: Hazard ratios for PFS by INV and BICR were consistent in each of the primary analysis and exploratory populations. In the ITT population, median PFS per INV was 23.5 months in the veliparib-throughout arm versus 17.3 months in the control arm (hazard ratio [HR] 0.683, 95% confidence interval [CI] 0.562-0.831; P < 0.001). Median PFS by BICR was 29.3 months versus 19.2 months (HR 0.687, 95% CI 0.504-0.806). In the ITT population, the overall concordance rates between INV and BICR were 78% and 75% for the veliparib-throughout and control arms, respectively.

Conclusions: Hazard ratios for PFS per BICR and per INV were consistent, with no suggestion of investigator bias. These findings support the reliability of PFS by INV in ovarian cancer trials.

Keywords: BICR; GOG-3005; Ovarian cancer; PARP inhibitor; Phase 3; VELIA; Veliparib.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Benzimidazoles / therapeutic use*
  • Carboplatin / therapeutic use
  • Carcinoma, Ovarian Epithelial / diagnosis
  • Carcinoma, Ovarian Epithelial / drug therapy*
  • Carcinoma, Ovarian Epithelial / mortality
  • Data Interpretation, Statistical
  • Female
  • Humans
  • Neoplasm Grading
  • Ovarian Neoplasms / diagnosis
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / mortality
  • Paclitaxel / therapeutic use
  • Progression-Free Survival
  • Reproducibility of Results
  • Research Design
  • Response Evaluation Criteria in Solid Tumors
  • Survival Analysis

Substances

  • Benzimidazoles
  • veliparib
  • Carboplatin
  • Paclitaxel