Previously, results from the phase 3 PAOLA-1/ENGOT-ov25 trial (NCT02477644) 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) was improved from 16.6 months with placebo/bevacizumab to 22.1. months with olaparib/bevacizumab (HR 0.59; P<0.001)1.
In patients with tumours positive for homologous recombination deficiency (HRD), including tumours 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 an OS benefit at 5 years2.
PAOLA-1 randomised 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) up to 15 months.
Median OS 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 arm, 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) arm, respectively (HR 0.62) Updated mPFS in the HRD-positive group was 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.
“This data shows 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,” concluded Dr Ray-Coquard.