Homologous Recombination Inquiry Through Ovarian Malignancy Investigations: The Japanese Gynecologic Oncology Group study JGOG3025

The Cancer Genome Atlas has clarified that about 50% of high-grade serous ovarian cancer shows homologous recombination deficiency (HRD). However, the frequency of HRD in Japanese patients with ovarian cancer remains unclear. The aim of JGOG3025 study (NCT03159572) is to identify the frequency of HRD in Japanese patients with ovarian cancer. The JGOG3025 study is a multicenter collaborative prospective observational study involving 65 study sites throughout Japan. We recruited 996 patients who were clinically diagnosed with ovarian cancer before surgery from March 2017 to March 2019, and 701 patients were eligible for JGOG3025 criteria. We used frozen tumor tissues to extract DNA and performed targeted sequencing for 51 genes most of which are HR-associated genes in 701 ovarian cancers (298 high-grade serous, 189 clear cell, 135 endometrioid, 12 mucinous, 3 low-grade serous, and 64 others). HRD was defined as positive when at least one HR-associated gene was mutated. The frequencies of HRD and tumor BRCA1/2 mutation were 45.2% (317/701) and 18.5% (130/701) in the full analysis set (FAS), respectively. Next, we performed multivariate Cox proportional hazards regression analysis for progression-free survival (PFS) and overall survival (OS). Advanced-stage ovarian cancer patients with HRD had an adjusted hazard ratio of 0.72 (95%CI, 0.55-0.93) and 0.58 (95%CI, 0.39-0.87) for PFS and OS compared to those without HRD (p = 0.013 and 0.009). Our study demonstrated that mutations in HR-associated genes might be associated with their prognosis. Further study will be needed to investigate prognostic impact of each HR-associated gene in ovarian cancer.