Rechallenge With Olaparib Maintenance Improved PFS Among Patients With Previously Treated, Platinum-Sensitive Ovarian Cancer

According to results from the phase 3b OReO/ENGOT-ov38 trial, rechallenging with olaparib in the maintenance setting significantly improved progression-free survival (PFS) among patients with previously treated, platinum-sensitive ovarian cancer regardless of BRCA status. 

“Poly (ADP-ribose) polymerase (PARP) inhibitor maintenance therapy is standard of care for some patients with advanced ovarian cancer,” stated Eric Pujade-Lauraine, MD, PhD, ARCAGY-GINECO, Paris, France, and coauthors. They added, “it is unknown if patients will benefit from rechallenge with PARPi maintenance therapy at relapse.” 

In this double-blind trial, patients with platinum-sensitive, relapsed ovarian cancer treated with first-line chemotherapy followed by either PARP inhibitor therapy or further lines of chemotherapy were enrolled and classified by BRCA status (BRCA-mutated or non-BRCA-mutated). Patients were randomized on a 2-to-1 basis to receive either 300 mg olaparib twice daily or placebo. The primary end point of the study was investigator-assessed PFS. 

In the BRCA-mutated cohort, 74 patients were assigned to receive olaparib and 38 were assigned to receive the placebo. In the non-BRCA-cohort, 72 patients were assigned to receive olaparib and 36 patients were assigned to receive the placebo. The median PFS of patients in the BRCA-mutated cohort was 4.3 months with olaparib and 2.8 months with placebo (hazard ratio [HR], 0.57; 95% confidence interval [CI] 0.37 to 0.87; P = .022). The median PFS of the non-BRCA-mutated cohort was 5.3 months with olaparib and 2.8 months with placebo (HR, 0.57; 95% CI 0.37 to 0.87; P = .022). The estimated 1-year PFS with olaparib was 19% among patients in the BRCA-mutated cohort and 14% in the non-BRCA-mutated cohort. No new safety signals were observed with olaparib rechallenge. 

“OReO is the first study to demonstrate that in a heavily pretreated ovarian cancer population, maintenance olaparib rechallenge provided a statistically significant, albeit modest, improvement in PFS compared with placebo, regardless of BRCA [mutation] status,” concluded Dr Pujade-Lauraine and coauthors. “Further investigation may reveal identifiable characteristics of those patients deriving the most clinical benefit.”

Source: 

Pujade-Lauraine E, Selle F, Scambia G, et al. Maintenance olaparib rechallenge in patients with platinum-sensitive relapsed ovarian cancer previously treated with a PARP inhibitor (OReO/ENGOT-ov38): A phase 3b trial. Ann Oncol. Published online: October 3, 2023. doi:10.1016/j.annonc.2023.09.3110