Independent radiologic review of GOG218, a phase III trial of bevacizumab (BEV) in the primary treatment of advanced epithelial ovarian (EOC), primary peritoneal (PPC) or Fallopian tube cancer (FTC).

Abstract

5023 Background: GOG218 is a phase III randomized, double-blind, placebo-controlled trial with three arms comparing both carboplatin and paclitaxel (CP) plus concurrent, or concurrent plus continued BEV (CP+B-->B) in stage III (with macroscopic residual disease) and stage IV EOC, PPC or FTC. Investigator assessment showed a clinically meaningful and statistically significant improvement in progression-free survival (PFS) for CP+B-->B when compared with CP therapy alone (R.A. Burger, ASCO 2010 LBA1). The PFS hazard ratios (HR) from the uncensored and censored (censored for CA-125 and non-protocol therapy, INVc) analyses were 0.72 (p< 0.0001) and 0.644 (p< 0.0001), respectively. To determine the reliability of RECIST in assessing progression in ovarian cancer, an independent review of blinded radiologic and clinical data was conducted to confirm these results. Methods: Radiographic images and clinical data were provided to the independent review committee (IRC). Data were reviewed in a blinded fashion, in accordance with a pre-specified charter following RECIST criteria. PFS was analyzed as an intent-to-treat analysis of all randomized subjects. Results: Images were submitted for over 97% of patients. High concordance between IRC and INVc was observed for progressive disease (PD) status (77%) and PD date (73%). Further analysis of concordance and validation of other study endpoints is ongoing. Conclusions: This is the largest IRC analysis ever conducted in patients with ovarian cancer, to our knowledge. The IRC and INVc PFS analyses were highly consistent, both confirming a significant increase in PFS for subjects treated with CP+B-->B versus CP alone. The size of the IRC, high participation rate, and strong concordance observed between IRC and INVc suggest that RECIST criteria can be applied objectively in primary ovarian cancers. IRC INVc CP N=625 CP+B-->B N=623* CP N=625 CP+B-->B N=623* PFS (HR) 0.630 0.644 P value (log rank) <0.0001 <0.0001 Median (months) 13.1 19.1 12.0 18.2 * Events prior to cycle 7 from the concurrent and CP + B-->B arms were pooled for analysis.