Abstract 731P
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-naïve (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. Table: 731P
| No. of patients in analysis | No. of events | Months, median (range) | |
| Co-primary endpointsN3 / N2 N4 / N3 | 1811 | 11/18 (61%, 95%CI 36-83%)4/11 (36%, 95%CI 11-69%) | -- |
| Secondary efficacy endpoints Progression-free survival (PFS)Time to first subsequent therapy (TFST)Progression-free survival 2 (PFS2) | 232323 | 201818 | 10.1 (2.7 – 34.0c)12.7 (4.0 – 34.0c)19.9 (7.0 – 35.2c) |
| Post-hoc exploratory analysis Chemotherapy-free interval 1 (platinum)Chemotherapy-free interval 2 (platinum/non-platinum)Duration on treatment OLAP1 (DOT-OLAP1)Duration on treatment OLAP2+/-Cediranib (DOT-OLAP2) | 23112311 | 1882111 | 14.1 (5.3 – 35.1c)7.8 (3.8 – 15.0c)10.1 (0.9 – 34.0c)3.4 (0.4 – 9.5) |
Key: N2, no. of patients who received PLAT2; N3, no. of patients who received one dose of OLAP2+/-Cediranib; N4, no. of patients who received OLAP2+/-Cediranib for ≥6 months; ccensored.
.Conclusions
No new safety concerns with OLAP2. OLAP2 demonstrated modest efficacy compared to OLAP1.
Clinical trial identification
NCT02855697.
Editorial acknowledgement
Legal entity responsible for the study
The Christie NHS Foundation Trust.
Funding
AstraZeneca and Merck Sharp & Dohme.
Disclosure
All authors have declared no conflicts of interest.