A single maintenance course of a poly(ADP-ribose) polymerase inhibitor (PARPi) improves progression-free survival (PFS) in germline BRCA1/2-mutant high-grade serous ovarian cancer (gBRCAm-HGSOC). The feasibility of a second maintenance course of PARPi was unknown.
Phase II trial with two entry points (EP1, EP2). Patients were recruited prior to rechallenge platinum. Patients with relapsed, gBRCAm-HGSOC were enrolled at EP1 if they were PARPi-naïve. Patients enrolled at EP2 had received their first course of olaparib prior to trial entry. EP1 patients were re-treated with olaparib after RECIST complete/partial response (CR/PR) to platinum. EP2 patients were re-treated with olaparib +/- cediranib after RECIST CR/PR/stable disease to platinum and according to platinum-free interval. Co-primary outcomes were the proportion of patients who received a second course of olaparib and the proportion who received olaparib re-treatment for ≥6 months. Functional homologous recombination deficiency (HRD), somatic copy-number alteration (SCNA) and BRCAm reversions were investigated in tumour and liquid biopsies.
Twenty-seven patients were treated (EP1=17,EP2=10) and 19 were evaluable. Twelve patients (63%) received a second course of olaparib and 4/12 received olaparib re-treatment for ≥6 months. Common grade ≥2 adverse events during olaparib re-treatment were anaemia, nausea and fatigue. No cases of MDS/AML occurred. Mean duration of olaparib treatment and re-treatment differed (12.1 versus 4.4 months; p<0.001). Functional HRD and SCNA did not predict PFS. A BRCA2m reversion was detected in a post-olaparib liquid biopsy.
A second course of olaparib can be safely administered to women with gBRCAm-HGSOC but is only modestly efficacious.
