Presentation Authors: Baijun Dong*, Liancheng Fan, Bin Yang, Shanghai, China, People's Republic of, Kaijie Wu, Xi'an, China, People's Republic of, Fengbo Zhang, Beijing, China, People's Republic of, Wei Chen, Wenzhou, China, People's Republic of, Huihua Cheng, Fuzhou, China, People's Republic of, Jiahua Pan, Yinjie Zhu, Chong Luo, Yining Yang, Guodong Zhao, Chunlong Wang, Shanghai, China, People's Republic of, Lei Li, Xi'an, China, People's Republic of, Xudong Yao, Wei Xue, Shanghai, China, People's Republic of
Introduction: To evaluate the predictive factors of circulating tumor DNA targeted sequencing in the efficacy of diverse treatment in mCRPC patients.
Methods: From 2016 to 2017, we recruited 67 mCRPC patients and performed targeted germline and somatic sequencing of 50 genes including DNA repair pathway and AR pathway etc. PSA-PFS were assessed in relation to initial ADT and subsequent therapy using Kaplan-Meier analysis.
Results: 58 mCRPC patients have plasma ctDNA fraction(ctDNA%, the proportion of tumor-derived cfDNA) above 2%. The matched primary tumor tissue biopsy of 5 patients and the matched metastatic tumor tissue biopsy of one patient were also sequenced. It showed 100% consistency between the metastatic tumor tissue and the matched plasma. However, 3 of 5 patients showed < 20% consistency between the primary tumor tissue and the matched plasma(other 2 of 5 patients showed 100% consistency between the primary tumor tissue and the matched plasma). In patients with ctDNA% above 2%, the most frequent mutated gene was AR(mutation or amplification). 32 of 58(55.2%) patients have genes alteration in DNA repair pathway, and the most frequent mutated genes were BRCA2, ATM and CDK12. In patients treated with abiraterone(AA), patients with BRCA2 and ATM pathogenic alteration had a worse clinical outcome even with primary resistance. However, these patients had similar response to docetaxel compared with wild type patients. The patients with P53 mutation had worse clinical outcomes compared with wild type patients.regardless of receiving AA or docetaxel treatment. 8 of 12(75%) patients with DNA repair pathway genes alteration which had received PARPi or platinum based chemotherapy showed initial response. Among these patients with initial response, 8 of 8 patients had germline or somatic pathogenic homologous recombinational repairï¼ˆHRRï¼‰pathway genes alteration.
Conclusions: It was the first multi-institutional study which explored the genomic alterations in Chinese mCRPC patients by liquid biopsy. These findings established genomic drivers of resistance to first-line and second line AR-targeted therapies and chemotherapy in mCRPC, which could identify minimally invasive biomarkers. Furthermore, our findings suggest that liquid biopsy analysis can guide the use of PARPi and platinum-based chemotherapy in general practice.