2022-RA-1290-ESGO Maintenance olaparib rechallenge in patients with ovarian cancer previously treated with a PARP inhibitor: detailed safety results from the Phase IIIb OReO/ENGOT-ov38 trial

Abstract

<h3>Introduction/Background</h3> 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 <i>BRCA1/BRCA2</i> (BRCA) mutation status. Safety data were consistent with olaparib during first use; overall, olaparib discontinuation due to adverse events (AEs) was low (Pujade-Lauraine <i>et al.</i> 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. <h3>Methodology</h3> Patients with PSROC in response to their most recent platinum-based chemotherapy, who had received one prior maintenance PARP inhibitor, were enrolled into BRCA<i>-</i>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. <h3>Results</h3> 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). <h3>Conclusion</h3> 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.