Carboplatin/pegylated liposomal doxorubicin/bevacizumab (CD-BEV) vs. carboplatin/gemcitabine/bevacizumab (CG-BEV) in patients with recurrent ovarian cancer: A prospective randomized phase III ENGOT/GCIG-Intergroup study (AGO study group, AGO-Austria, ANZGOG, GINECO, SGCTG)

Abstract

Background: In patients with recurrent ovarian cancer (ROC) suitable for platinumbased retreatment (PBT), standard includes CG‐BEV and Carboplatin(C)/pegylatedliposomal‐ Doxorubicin (D). CG‐BEV significantly increases progression‐free‐survival (PFS) over CG alone whilst CD has one of the best therapeutic indices for ROC‐PBT. The aim of this trial was to evaluate whether CD is superior to CG when given in combination with BEV with investigator‐determined PFS as primary objective (NCT01837251). Methods: Between 2013/08 and 2015/07 682 pts. with ROC‐PBT were randomized to standard CG‐BEV (n=337) or experimental CD‐BEV (n=345). Secondary objectives were overall survival (OS), biological progression‐free survival (PFSBIO) by serum CA125, quality of life (QoL) assessed by EORTC‐QLQ‐C30 and QLQ‐OV28, safety and tolerability. The trial was designed to have 80% power (two‐sided logrank‐test, alpha level 5%) to show a 26.6% change in PFS (Hazard Ratio (HR) 0.79; 564 PFS events). Results: At data cut‐off 571 events occurred. Mean age was 61.1 (SD 10.3) years, 87.4% had serous histology, 83.1% were high grade, 41.5% were pretreated with BEV as part of first‐line treatment. CG‐BEV was associated with 359 (53,3%) serious adverse events vs. 314 (46,7%) for CD‐BEV (p=0.083). Median PFS in the standard arm CG‐BEV was 11.7 months (95% CI 11.1‐12.8) vs. 13.3months (95% CI 11.7‐14.3) in the experimental arm CD‐BEV (HR 0.80; 95% CI 0.68‐0.96, p=0.0128). In the stratum with previous anti‐angiogenic treatment (N=309) median PFS was 10.1 months (95% CI 8.5‐ 11.2) for CG‐BEV vs. 11.3 months (95% CI 10.1‐13.8) for CD‐BEV (HR 0.73; 95% CI 0.57‐0.94, p=0.0126). Conclusions: CD‐BEV provided a significant PFS improvement compared to CG‐BEV in patients with ROC suitable for PBT. A significant PFS improvement was also seen in the subgroup of patients with previous anti‐angiogenic treatment. CD‐BEV was associated with fewer serious adverse events. Thus CD‐BEV might be an important addition to the therapeutic options in these patients.