OS benefit for advanced ovarian cancer patients treated with maintenance olaparib

The addition of maintenance olaparib to bevacizumab provided a clinically meaningful overall survival (OS) benefit in homologous recombination deficiency (HRD)-positive patients, results from the final analysis of the phase 3 PAOLA-1/ENGOT-ov25 trial showed.

Earlier analyses from the PAOLA-1/ENGOT-ov25 trial (NCT02477644) showed significant benefits in progression-free survival (PFS) 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 [1]. Prof. Isabelle Ray-Coquard (Centre Léon Bérard, France) presented the final PAOLA-1/ENGOT-ov25 trial analysis, which investigated whether the PFS advantages observed in the primary analysis translated to an OS benefit at 5 years [2].

The PAOLA-1/ENGOT-ov25 trial 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 participants received bevacizumab (15 mg/kg every 3 weeks) for up to 15 months.

The median OS in the intention-to-treat population was 56.5 months in the olaparib plus bevacizumab arm versus 51.6 months in the placebo plus bevacizumab arm (HR 0.92; P=0.4118). At 5 years of follow-up, 47.3% versus 41.5% of participants were still alive in the olaparib plus bevacizumab and placebo plus bevacizumab arm, respectively. A total of 45.7% of participants in the placebo plus bevacizumab arm received a PARP inhibitor during any subsequent treatment versus 19.6% of participants in the olaparib plus bevacizumab arm.

In HRD-positive patients, the median OS was 75.2 months for olaparib plus bevacizumab-treated participants (n=255) compared with 57.3 months in the placebo plus bevacizumab (n=133) arm (HR 0.62, see Figure). No OS benefit was observed in HRD-negative patients (36.8 months for olaparib vs 40.4 months for placebo; HR 1.19). The updated median PFS in the HRD-positive group was 46.8 months and 17.6 months for olaparib plus bevacizumab- and placebo plus bevacizumab-treated participants respectively (HR 0.41). 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, the addition of maintenance olaparib to bevacizumab provided a clinically meaningful OS benefit in HRD-positive patients,” concluded Prof. Ray-Coquard.

1. Ray-Coquard IL, et al. N Engl J Med 2019;381(25):2416–2428.
2. Ray-Coquard IL, et al. Final overall survival (OS) results from the phase III PAOLA-1/ENGOT-ov25 trial evaluating maintenance olaparib (ola) plus bevacizumab (bev) in patients (pts) with newly diagnosed advanced ovarian cancer (AOC). Abstract LBA29, ESMO Congress 2022, 09–13 September, Paris, France.

Figure: Overall survival was prolonged in the HRD-positive subgroup [2].



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Posted on 17 November, 20226 September, 2023