Maintenance olaparib rechallenge in patients with platinum-sensitive relapsed ovarian cancer previously treated with a PARP inhibitor (OReO/ENGOT-ov38): a phase IIIb trial
Mené sur 74 patientes atteintes d'un cancer de l'ovaire sensible aux sels de platine et récidivant, cet essai de phase IIIB évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité de l'olaparib en traitement d'entretien après l'échec d'un traitement par inhibiteur de PARP et au moins deux lignes de chimiothérapie à base de sels de platine
Background: Poly(ADP-ribose) polymerase (PARP) inhibitor maintenance therapy is standard of care for some patients with advanced ovarian cancer. We evaluated the efficacy and safety of PARP inhibitor rechallenge. Patients and methods: This randomized, double-blind, multicenter trial (NCT03106987) enrolled patients with platinum-sensitive relapsed ovarian cancer who had received one prior PARP inhibitor therapy for ≥18 and ≥12 months in the BRCA-mutated and non-BRCA-mutated cohorts, respectively, following first-line chemotherapy or for ≥12 and ≥6 months, respectively, following a second or subsequent line of chemotherapy. Patients were in response following their last platinum-based chemotherapy regimen and were randomized 2:1 to maintenance olaparib tablets 300 mg twice daily or placebo. Investigator-assessed progression-free survival (PFS) was the primary endpoint. Results: 74 patients in the BRCA-mutated cohort were randomized to olaparib and 38 to placebo, and 72 patients in the non-BRCA-mutated cohort were randomized to olaparib and 36 to placebo; >85% of patients in both cohorts had received ≥3 prior lines of chemotherapy. In the BRCA-mutated cohort, median PFS was 4.3 months with olaparib versus 2.8 months with placebo (hazard ratio [HR] 0.57; 95% confidence interval [CI] 0.37-0.87; P = 0.022); 1-year PFS rates were 19% versus 0% (Kaplan–Meier estimates). In the non-BRCA-mutated cohort, median PFS was 5.3 months for olaparib versus 2.8 months for placebo (HR 0.43; 95% CI 0.26-0.71; P = 0.0023); 1-year PFS rates were 14% versus 0% (Kaplan–Meier estimates). No new safety signals were identified with olaparib rechallenge. Conclusions: In ovarian cancer patients previously treated with one prior PARP inhibitor and at least two lines of platinum-based chemotherapy, maintenance olaparib rechallenge provided a statistically significant, albeit modest, PFS improvement over placebo in both the BRCA-mutated and non-BRCA-mutated cohorts, with a proportion of patients in the maintenance olaparib rechallenge arm of both cohorts remaining progression free at 1 year.
Annals of Oncology 2023