Introduction/Background OReO/ENGOT-ov38 (NCT03106987) demonstrated a statistically significant progression-free survival benefit with maintenance olaparib rechallenge versus placebo in patients with platinum-sensitive relapsed ovarian cancer (PSROC), irrespective of BRCA1/BRCA2 (BRCA) mutation status. Safety data were consistent with olaparib during first use; overall, olaparib discontinuation due to adverse events (AEs) was low (Pujade-Lauraine et al. ESMO 2021). We further characterised the tolerability of maintenance olaparib rechallenge in OReO/ENGOT-ov38, including time to onset and duration of selected AEs deemed relevant to olaparib.

Methodology Patients with PSROC in response to their most recent platinum-based chemotherapy, who had received one prior maintenance PARP inhibitor, were enrolled into BRCA-mutated or non-BRCA-mutated cohorts. In each cohort, patients were randomised 2:1 to maintenance olaparib (300 mg) or placebo bid until disease progression. Safety and tolerability were assessed in patients receiving ≥1 dose. AEs were monitored during treatment and for 30 days after discontinuation.

Results All 220 enrolled patients were included in the safety analyses (BRCA-mutated, n=112 [olaparib, n=74; placebo, n=38]; non-BRCA-mutated, n=108 [olaparib, n=72; placebo, n=36]). At data cutoff, 8 (7%) and 27 (25%) patients in the BRCA-mutated and non-BRCA-mutated cohorts, respectively, were still receiving treatment. In the BRCA-mutated cohort (olaparib arm), median time to first occurrence of nausea, vomiting, fatigue/asthenia, and anaemia was ≤32 days (table 1). Median durations of first events of nausea, vomiting, neutropenia, and thrombocytopenia were ≤38 days (table 1 for placebo comparison). In the non-BRCA-mutated cohort (olaparib arm), median time to first occurrence of all AEs was ≤29 days, excluding anaemia (table 2). Duration of first events of nausea, vomiting, neutropenia, and thrombocytopenia was ≤36 days (table 2 for placebo comparison). No cases of MDS/AML were reported (olaparib arm).

Conclusion In patients with PSROC who received maintenance olaparib rechallenge, AEs usually occurred early and were generally manageable, consistent with the known safety profile of olaparib.