Objectives: Gynecologic Oncology Group Study 0218 (GOG-0218), a phase III, placebo-controlled trial in newly diagnosed stage III/IV ovarian cancer (OC), demonstrated a benefit in investigator (INV)-assessed progression-free survival (PFS) with bevacizumab (BEV) administered with and following carboplatin/paclitaxel (CP) for up to 15 months vs. CP alone. To determine the reliability of Response Evaluation Criteria in Solid Tumors (RECIST) in assessing disease progression (PD) in GOG-0218, an independent review of radiologic and clinical data (IRC) was conducted.
Methods: Blinded reviews followed RECIST 1.0 in accordance with the study protocol; PFS was analyzed in the intent-to-treat population.
Results: CP+BEV→BEV achieved a significant PFS improvement in both assessments. Hazard ratios for PFS (IRC: 0.623; 95% confidence interval [CI]: 0.503-0.772; p<0.0001 vs. INV: 0.624; 95% CI: 0.520-0.749; p<0.0001) and the improvement in median PFS (IRC: 19.1 and 13.1 months vs. INV: 18.2 and 12 months) were similar between IRC and INV assessments. There was high concordance between IRC- and INV-determined PD status (77%) and date (73%). Subgroup analyses were consistent with the primary IRC findings. Early and late discontinuation discordance measures showed no evidence of INV bias.
Conclusion: IRC analysis confirmed a significant PFS improvement with CP+BEV→BEV vs. CP alone. Concordance was not influenced by extent of residual disease after cytoreductive surgery or initial stage. The IRC size, high participation rate, and strong concordance between IRC and INV assessments suggest that RECIST can be applied objectively in OC studies.
Keywords: Bevacizumab; IRC; Independent review; Ovarian cancer; Phase 3.
© 2013.