Abstract 659: Evaluation of homologous recombination repair related gene mutation on survival and drug response in Chinese epithelial ovarian cancer patients

Abstract

Abstract Background: Target sequencing of epithelial ovarian cancer (EOC) has been widely used in clinical to detect the status of BRCA1/2 and genes in homologous recombination repair (HRR) pathway. But there still lacks of systematic evaluation of HRR related gene mutation effect on clinical outcome. Methods: Totally 230 EOC patient is recruited and received OseqT panel sequencing including 12 HRR related genes, 5 mismatch repair related genes and 8 ovarian cancer related genes. All the patients received platinum-based chemotherapy. 25 of them received PARP inhibitor therapy. Their responses to the therapy, OS and PFS were collected for analysis. Results: We found that BRCA2 and BRCA1/2 mutation carriers (somatic and germline) had longer OS (p value: 0.016 and 0.028) and PFS (p value: 0.002, 0.006) than non-carriers, PTEN and MSH2 germline mutation carriers had longer PFS (p value: 0.038, 0.049) than non-carries. When we compared germline pathogenic carriers and non-pathogenic carriers on OS and PFS, there is significant difference in PALB2 (p value: 0.036, 0.015) and STK11 (0.001, 0.018), BRCA1 mutation did not affect survival time in both OS and PFS. Then we observed the response to platinum-based chemotherapy. We found that the carriers of germline pathogenic variants in BRCA1, BRCA1/2 and HRR related genes were significant related with better response (p value: 0.16, 0.042 and 0.048), If we combined germline and somatic pathogenic variants together, the p value of BRCA1, BRCA1/2 and HRR related genes were changed to 0.001, 0.009 and 0.001. Somatic status of those gene alone had no relationship with chemotherapy response.In the patients received treatment of PARP inhibitor Niraparib, carriers of germline and somatic pathogenic variant in BRCA1 and BRCA1/2 were more sensitive to Niraparib (p value: 0.18, 0.008), There was only 1 BRCA2 pathogenic carrier and no other HRR related gene pathogenic carrier in 25 patients. So, the sensitivity of BRCA2 and HRR-related gene mutation carriers were not calculated. Conclusions: In our cohort, BRCA2 and BRCA1/2 mutation carriers had longer OS and PFS than non-carriers. PTEN, MSH2, PALB2 and STK11 mutation status also had relationship with survival in some circumstances, BRCA1, BRCA1/2 and HRR-related genes could all be used to predict drug sensitivity, germline and somatic variant should be combined used to reach better performance. Citation Format: Lei Li, Kang Shao, Jianwei Zhang, Meng Liu, Kui Wu, Ming Wu. Evaluation of homologous recombination repair related gene mutation on survival and drug response in Chinese epithelial ovarian cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 659.