The phase 3 PAOLA/ENGOT-ov25 study assessed the outcomes of adding olaparib (OLA) to maintenance bevacizumab (BEV) after first-line platinum-based chemotherapy with BEV for patients with newly diagnosed high-grade ovarian cancer. The significant improvement associated with the addition of OLA in terms of progression-free survival (PFS) has been previously reported (hazard ratio [HR], 0.59; 95% confidence interval [CI], 0.49-0.72). However, in the initial report, second PFS (PFS2) data were not yet complete. The authors report the data here.
In this study, 537 patients were randomized to receive OLA (300 mg twice daily for 24 months) + BEV (15 mg/kg once every 3 weeks for 15 months), and 269 patients were randomized to receive placebo + BEV. These patients had already received first-line treatment of upfront or interval surgery and platinum-taxane–based chemotherapy plus at least 2 cycles of BEV. The randomization was stratified by tumor BRCA status and first-line treatment outcomes. PFS2 and time to second subsequent therapy (TSST) or death were secondary end points.
The median PFS2 was 36.5 months for the OLA + BEV arm and 32.6 months for the placebo + BEV arm (HR, 0.78; 95% CI, 0.64-0.95; P = .0125). There were also fewer events per patient in the OLA + BEV arm (48%) than the placebo + BEV arm (61%). In a subgroup analysis of patients by homologous recombination deficiency (HRD) status, OLA + BEV resulted in improved PFS2 over placebo + BEV for HRD-positive patients, regardless of whether those with tumor BRCA-mutated status were included in the analysis. For all HRD-positive patients, median PFS2 was 50.3 months with OLA + BEV versus 35.3 months for placebo + BEV (HR, 0.56; 95% CI, 0.41-0.77), and for the HRD-positive subgroup without tumor BRCA mutated, median PFS2 was 50.3 months for OLA + BEV versus 30.1 months for placebo + BEV (HR, 0.60; 95% CI, 0.38-0.96). For those with HRD-negative or unknown status, OLA + BEV and placebo + BEV resulted in similar median PFS2; 26.3 months and 28.1 months, respectively (HR, 0.98; 95% CI, 0.77-1.27).
The benefit of treatment with OLA + BEV was further supported by a statistically significant improvement in TSST. Median TSST for the OLA + BEV arm was 38.2 months versus 31.5 months for the placebo + BEV arm (HR, 0.78; 95% CI, 0.64-0.95; P = .0115). For the tumor BRCA mutated and the HRD-positive subgroups, OLA + BEV also resulted in an improved TSST, with corresponding HR values of 0.48 (95% CI, 0.31-0.75) and 0.48 (95% CI, 0.35-0.66) for these subgroups, respectively. However, for HRD-negative or unknown patients, there was not a significant difference in TSST (HR, 1.05; 95% CI, 0.82-1.36). No new safety signals have been detected in patients in the active arm with longer follow-up.
In summary, the addition of maintenance OLA + BEV provided benefit beyond initial progression, significantly improving PFS2, particularly in HRD-positive patients. This outcome was supported by a delay in TSST. Overall survival data will be provided at a later time, as they are still immature.
Abstract and Late-Breaking Oral Presentation LBA33. ESMO 2020. September 21, 2020. Maintenance olaparib plus bevacizumab (bev) in patients (pts) with newly diagnosed advanced high‐grade ovarian carcinoma (HGOC): final analysis of second progression-free survival (PFS2) in the phase III PAOLA-1/ENGOT-ov25 trial.