Addition of maintenance olaparib to bevacizumab provides a clinically meaningful overall survival benefit in patients who are HRD-positive, results from the final analysis of the PAOLA-1 trial show.
Results from the phase 3 PAOLA-1/ENGOT-ov25 trial showed clinical benefit of maintenance olaparib plus bevacizumab therapy in patients with newly diagnosed advanced ovarian cancer who had received first-line standard-of-care treatment including bevacizumab. Median progression-free survival (mPFS) improved from 16.6 months with placebo/bevacizumab to 22.1. months with olaparib/bevacizumab (HR, 0.59; P<0.001). In patients with tumors positive for homologous recombination deficiency (HRD), including tumors that had BRCA mutations, clinical benefit was even more pronounced (mPFS, 37.2 vs 17.7 months; HR, 0.33).
Dr. Isabelle Ray-Coquard (Centre Léon Bérard, France) presented the final PAOLA-1 analysis, which investigates whether the PFS advantages observed in the primary analysis translates to overall survival (OS) benefit at 5 years. PAOLA-1 randomized 806 patients with newly diagnosed, advanced, high-grade ovarian cancer who had a response after first-line platinum-taxane chemotherapy plus bevacizumab 2:1 to receive olaparib (300 mg twice daily) or placebo for 2 years. All patients received bevacizumab (15 mg/kg every 3 weeks) for up to 15 months.
Median OS (mOS) in the intention-to-treat population was 56.5 months in the olaparib/bevacizumab arm versus 51.6 months in the placebo/bevacizumab arm (HR, 0.92; P=0.4118) At 5 years of follow-up, 47.3% versus 41.5% were still alive in the olaparib/bevacizumab and placebo/bevacizumab arms, respectively. A total of 45.7% of patients in the placebo/bevacizumab arm received a PARP inhibitor during any subsequent treatment, versus 19.6% of patients in the olaparib/bevacizumab arm.
In the HRD-positive subgroup, mOS was 75.2 months versus 57.3 months in the olaparib/bevacizumab (n=255) and placebo/bevacizumab (n=133) arms, respectively (HR, 0.62) Updated mPFS times in the HRD-positive group were 46.8 months and 17.6 months, respectively (HR, 0.41). No OS benefit was seen in HRD-negative patients (36.8 vs 40.4 months; HR, 1.19). No new safety signals were observed.
“[These] data [show] that, despite a high proportion of patients in the control arm receiving a PARP inhibitor post-progression, addition of maintenance olaparib to bevacizumab provided a clinically meaningful OS benefit in patients who are HRD-positive,” said Dr. Ray-Coquard.
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