Multi-maintenance olaparib in relapsed, platinum-sensitive BRCA-mutant high-grade serous ovarian carcinoma (MOLTO): A phase II feasibility study

Abstract

Background Relapsed, platinum-sensitive high-grade serous ovarian carcinoma (RPS-HGSOC) is treated with platinum re-challenge. One course of olaparib maintenance monotherapy (OLAP1) improves PFS in RPS-HGSOC. It is unclear whether a second olaparib maintenance monotherapy course (OLAP2) in RPS-HGSOC following platinum re-challenge (PLAT2) is feasible. Methods Single centre, non-randomised, phase II study to determine feasibility of OLAP2 after response to PLAT2 in BRCAm RPS-HGSOC. Co-primary endpoints: 1) percentage of patients that started PLAT2 who received one dose of OLAP2 (N3/N2) and; 2) percentage of patients who received OLAP2+/-Cediranib ?6 months (N4/N3). Two trial entry points (EPs) pre-PLAT: 1) olaparib-na�ve (EP1, Pre-PLAT1) and; 2) OLAP1 pre-treated (EP2, Pre-PLAT2). If PFI ?6months on OLAP1, patient offered OLAP2. If PFI <6months on OLAP1, patient offered OLAP2+Cediranib. Results Between May 2017 and September 2019, 27 patients were enrolled (N1;EP1=17; EP2=10). BRCA1:BRCA2 22:5. Age range: 44-78 years. Three (median) lines of platinum chemotherapy prior to OLAP1. N=23 responded to PLAT1 and received OLAP1. N=18 received PLAT2 (N2) and N=11 achieved RECIST CR/PR/SD to PLAT2 and subsequently received OLAP2+/-Cediranib (N3/N2=61%). N=4 completed ?6 months OLAP2 (N4/N3=36%). Commonest grade 2-3 AEs during OLAP2 were anaemia (n=3 G2, n=1 G3), abdominal pain (n=1 G2, n=2 G3), fatigue (n=1 G2, n=2 G3), nausea (n=3 G2). No cases of AML/MDS, pneumonitis/ILD or new secondary malignancy were reported. Key efficacy endpoints in the table. Tumour and ctDNA HRD/CNV-based concurrent biomarker study will also be presented. Conclusions No new safety concerns with OLAP2. OLAP2 demonstrated modest efficacy compared to OLAP1.