Long‐term use and risk of major adverse cardiac events: Comparing enzalutamide and abiraterone in chemotherapy‐naïve patients with metastatic castration‐resistant prostate cancer

• Published in: International journal of cancer Vol. 152; no. 6; pp. 1191 - 1201
• Main Authors: Chen, Hung‐Kai, Su, Po‐Jung, Wang, Yan‐Lin, Chang, Kai‐Cheng, Su, Yu‐Li, Chang, Pei‐Hung, Kuan, Feng‐Che, Hsieh, Chia‐Hsun, Kuo, Yung‐Chia, Sheng, Ting‐Wen, Chang, Ching‐Fu, Yu, Shao‐Ming, Huang, Wen‐Kuan, Lin, Yung‐Chang, Tsan, Din‐Li, Yu, Kai‐Jie, Lin, Po‐Hung, Chen, Hui‐Yu, Chang, Ying‐Hsu, Pang, See‐Tong, Chuang, Cheng‐Keng, Lai, Edward Chia‐Cheng
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 15.03.2023; Wiley Subscription Services, Inc
• Subjects: androgen receptor targeted therapies; Androgen receptors; Cancer; Cardiovascular Diseases; Castration; Chemotherapy; Electronic medical records; Heart; Humans; major adverse cardiac events; Male; Medical research; Metastases; Metastasis; metastatic castration‐resistant prostate cancer; Nitriles - therapeutic use; Patients; Prostate cancer; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant - drug therapy; Prostatic Neoplasms, Castration-Resistant - pathology; Response rates; Retrospective Studies; Survival; Treatment Outcome; major adverse cardiac events; metastatic castration-resistant prostate cancer; androgen receptor targeted therapies
• ISSN: 0020-7136; 1097-0215; 1097-0215
• DOI: 10.1002/ijc.34348

This is a retrospective cohort study by analyzing a multi‐institutional electronic medical records database in Taiwan to compare long‐term effectiveness and risk of major adverse cardiac events (MACE) in chemotherapy‐naïve metastatic castration‐resistant prostate cancer (mCRPC) patients treated with enzalutamide (ENZ) or abiraterone (AA). Patients aged 20 years and older and newly receiving androgen receptor targeted therapies ENZ or AA from September 2016 to December 2019 were included. We followed patients from initiation of therapies to the occurrence of outcomes (prostate‐specific antigen (PSA) response rate, PSA progression free survival (PFS), overall survival (OS), and MACE), death, the last clinical visit, or December 31, 2020. We performed multivariable Cox proportional hazard models to compare ENZ and AA groups for the measured outcomes. A total of 363 patients treated with either ENZ (n = 157) or AA (n = 206) were identified. The analysis found a significantly higher proportion of patients with a PSA response rate higher than 50% among those receiving ENZ than among those receiving AA (ENZ vs AA: 75.80% vs 63.59%, P = .01). However, there was no significant difference in PSA PFS (adjusted hazard ratio: 0.86; 95% CI 0.63‐1.17) and OS (0.68: 0.41‐1.14) between the use of ENZ and AA in chemotherapy‐naïve mCRPC patients. Regarding the cardiovascular (CV) safety outcome, there was a significantly lower risk of MACE in patients receiving ENZ, compared to patients receiving AA (0.20: 0.07‐0.55). The findings suggest that enzalutamide may be more efficacious for PSA response and suitable for chemotherapy‐naïve mCRPC patients with high CV risk profile. What's new? While second generation androgen receptor (AR)‐targeted therapies are promising for the treatment of chemotherapy‐naïve metastatic castration‐resistant prostate cancer (mCRPC), data on survival benefit and cardiovascular safety are lacking. Here, using a multi‐institutional electronic health records database, the authors investigated the effectiveness, long‐term outcome, and cardiovascular safety of the AR‐targeted mCRPC therapies enzalutamide and abiraterone. Compared to abiraterone, enzalutamide is more efficacious in terms of prostate‐specific antigen response and carries a lower risk of major adverse cardiac events. The findings are relevant for treatment decisions regarding AR‐targeted therapies for chemotherapy‐naïve mCRPC patients with high risk of adverse cardiovascular events.