Abstract 534P
Background
Olaparib, a PARP inhibitor, has demonstrated efficacy as maintenance therapy in patients with newly diagnosed BRCA mutated or homologous recombination deficiency (HRD)-positive advanced ovarian cancer and as maintenance therapy in platinum-sensitive recurrent ovarian cancer. Furthermore, a synergistic effect between PARP inhibitors and immune checkpoint inhibitors has been suggested in preclinical studies and the efficacy of the combination is being demonstrated in clinic. However, the efficacy and safety of PARP inhibitors alone or in combination with immune checkpoint inhibitors as neoadjuvant therapy are unknown.
Methods
This is an open-label, multicenter pilot study evaluating the efficacy and safety of olaparib alone (cohort 1) or in combination with pembrolizumab (cohort 2) as neoadjuvant therapy in patients with HRD-positive stage III-IV ovarian cancer. In cohort 1 (n=10), patients received olaparib 300 mg orally twice daily for 6 weeks. In cohort 2 (n=20), patients received olaparib 300 mg orally twice daily for 6 weeks and pembrolizumab 200 mg was administered intravenously every 3 weeks for 2 cycles. The major inclusion criteria included newly diagnosed HRD-positive International Federation of Gynecology and Obstetrics (FIGO) stage III-IV high-grade serous or endometrioid ovarian, fallopian or primary peritoneal cancer. The primary endpoint was objective response rate (ORR) based on RECIST version 1.1. The results of cohort 1 are presented here.
Results
In total, 10 patients were enrolled in cohort 1. The median age was 67.5 (59-68), and all patients had high-grade serous carcinoma histology. Three patients had stage IIIC, 2 patients had stage IVA, and 5 patients had stage IVB. ORR was 50% (95% CI, 18.7-81.3). The proportion of grade 3 or higher adverse events was 40%, and the proportion of treatment discontinuation due to adverse events was 10%. Common adverse events were nausea (n=7), diarrhea (n=4) and fatigue (n=2).
Conclusions
Neoadjuvant olaparib monotherapy showed efficacy and tolerability in patients with HRD-positive advanced ovarian cancer. A pilot study of neoadjuvant combination treatment of olaparib plus pembrolizumab (cohort 2) is ongoing.
Clinical trial identification
NCT04417192.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Merck.
Disclosure
K. Harano: Financial Interests, Institutional, Research Grant: Merck, Daiichi-Sankyo; Financial Interests, Personal, Invited Speaker: AstraZeneca, Takeda; Financial Interests, Personal, Advisory Board: Chugai. K. Takehara: Financial Interests, Personal, Invited Speaker: Taiho, Abbvie, Eisai, Mochida, AstraZeneca, Takeda, Chugai; Financial Interests, Institutional, Research Grant: Chugai. G. Ishii: Financial Interests, Personal, Invited Speaker: Takeda, Taiho, Roche Diagnostics, Chugai, Novartis, Oncolys BioPharma, Daiichi-Sankyo, Eli Lilly; Financial Interests, Institutional, Research Grant: Organogenix, Daiichi-Sankyo, Ono, Novartis, Noile-Immune Biotech, Takeda, Sumitomo Dainippon Pharma, Nihon Medi-Physics. T. Mukohara: Financial Interests, Institutional, Research Grant: Merck, Daiichi-Sankyo, Sysmex; Financial Interests, Personal, Invited Speaker: MSD, Pfizer, Sanofi, Chugai. All other authors have declared no conflicts of interest.