关键词: 前列腺癌, 氟唑帕利, 同源重组修复缺陷, 有效性

Abstract: Background and purpose: Inhibitors of poly (ADP-ribose) polymerase (PARPi) has been shown in multiple clinical trials to benefit survival in patients with homologous recombination repair (HRR) gene mutations in metastatic castration-resistant prostate cancer (mCRPC). Fluzoparib has been approved for the treatment of ovarian, fallopian tube and peritoneal cancers, but no data have been reported for prostate cancer. The purpose of this study was to evaluate the efficacy and safety of fluzoparib in the treatment of patients with prostate cancer. Methods: The clinical data of 13 mCRPC patients treated with fluzoparib alone or fluzoparib combined with abiraterone or SHR3680 (androgen receptor antagonist) in 9 hospitals nationwide including Fudan University Shanghai Cancer Center from January 1, 2020 to February 1, 2021 were retrospectively analyzed. Genetic mutation data, survival data, adverse reactions and other data were obtained through outpatient cases or telephone follow-up. Results: Among the 13 patients, 3 patients were treated with fluzoparib alone, 8 patients were treated with fluzoparib combined with abiraterone, and 2 patients were treated with fluzoparib combined with SHR3680. All the 3 patients treated with monotherapy carried HRR gene mutations, and all had prostate-specific antigen (PSA); among those, 2 patients (66.7%) had PSA decrease of more than 50%. All the 8 patients treated with fluzoparib combined with abiraterone had been resistant to abiraterone at the earlier stage, and the genetic testing results showed that 2 patients did not carry HRR pathogenic mutation, and 1 patient did not receive genetic testing. Among the 8 patients, only 1 patient without HRR pathogenic mutation had an increase in PSA after receiving the combined treatment, while the remaining 7 patients (87.5%) had a decrease in PSA. PSA decreased by more than 50% in 3 patients (37.5%) and 90% in 2 patients (25.0%). The 2 patients treated with fluzoparib combined with SHR3680 had been resistant to abiraterone and docetaxel at the earlier stage, one patient had no genetic test and no PSA response, and the other patient had no DNA damage repair (DDR) gene mutation, however, decreased by more than 50%. At the same time, 61.5% (8/13) of the patients showed different degrees of adverse reactions, the main adverse reactions were anemia, joint pain, loss of appetite and fatigue; 23.1% (3/13) of the patients developed grade 3 anemia, of whom 1 patient terminated the treatment. Conclusion: Fluzoparib shows promising clinical prospects, and is well tolerated in both monotherapy and combination therapy. However, this conclusion needs to be further confirmed in prospective clinical studies with larger sample size.

Key words: Prostate cancer, Fluzoparib, Homologous recombination repair deficiency, Efficacy