Abstract：
OBJECTIVE: Abiraterone acetate (abiraterone) plus prednisone is approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC). Our aim was to evaluate the efficacy and safety of pembrolizumab plus abiraterone in mCRPC.
METHODS: In cohort D of the phase 1b/2 KEYNOTE-365 study (NCT02861573), patients were chemotherapy-naïve, had disease progression ≤6 mo before screening, and had either not received prior next-generation hormonal agents for mCRPC or had received prior enzalutamide for mCRPC and had disease progression or became intolerant to enzalutamide. Patients received pembrolizumab 200 mg intravenously every 3 wk plus abiraterone 1000 mg orally once daily and prednisone 5 mg orally twice daily. The primary endpoints were safety, prostate-specific antigen (PSA) response rate, and objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) by blinded independent central review (BICR). Secondary endpoints included radiographic progression-free survival (rPFS) according to Prostate Cancer Clinical Trials Working Group 3-modified RECIST v1.1 by BICR and overall survival (OS).
UNASSIGNED: For the 103 patients who were treated, median follow-up was 28 mo (interquartile range 26-31). The confirmed PSA response rate was 56% (58/103 patients). The ORR for patients with RECIST v1.1-measurable disease was 16% (6/37 patients). Median rPFS was 15 mo (95% confidence interval 9.2-22) and median OS was 30 mo (95% confidence interval 23-not reached); the estimated 24-mo OS rate was 58%. In total, 91% of patients experienced treatment-related adverse events, and 39% experienced grade 3-5 events. Grade 3/4 elevation of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) was observed in 12% and 6.8% of patients, respectively. One patient died due to treatment-related myasthenic syndrome. Study limitations include the single-arm design.
CONCLUSIONS: Pembrolizumab plus abiraterone and prednisone demonstrated antitumor activity and acceptable safety in patients with chemotherapy-naïve mCRPC. Higher incidence of grade 3/4 elevated ALT/AST occurred than was reported for the individual agents.
RESULTS: For patients with metastatic castratation-resistant prostate cancer, the drug combination of pembrolizumab plus abiraterone and prednisone showed antitumor activity and acceptable safety.
METHODS: In cohort D of the phase 1b/2 KEYNOTE-365 study (NCT02861573), patients were chemotherapy-naïve, had disease progression ≤6 mo before screening, and had either not received prior next-generation hormonal agents for mCRPC or had received prior enzalutamide for mCRPC and had disease progression or became intolerant to enzalutamide. Patients received pembrolizumab 200 mg intravenously every 3 wk plus abiraterone 1000 mg orally once daily and prednisone 5 mg orally twice daily. The primary endpoints were safety, prostate-specific antigen (PSA) response rate, and objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) by blinded independent central review (BICR). Secondary endpoints included radiographic progression-free survival (rPFS) according to Prostate Cancer Clinical Trials Working Group 3-modified RECIST v1.1 by BICR and overall survival (OS).
UNASSIGNED: For the 103 patients who were treated, median follow-up was 28 mo (interquartile range 26-31). The confirmed PSA response rate was 56% (58/103 patients). The ORR for patients with RECIST v1.1-measurable disease was 16% (6/37 patients). Median rPFS was 15 mo (95% confidence interval 9.2-22) and median OS was 30 mo (95% confidence interval 23-not reached); the estimated 24-mo OS rate was 58%. In total, 91% of patients experienced treatment-related adverse events, and 39% experienced grade 3-5 events. Grade 3/4 elevation of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) was observed in 12% and 6.8% of patients, respectively. One patient died due to treatment-related myasthenic syndrome. Study limitations include the single-arm design.
CONCLUSIONS: Pembrolizumab plus abiraterone and prednisone demonstrated antitumor activity and acceptable safety in patients with chemotherapy-naïve mCRPC. Higher incidence of grade 3/4 elevated ALT/AST occurred than was reported for the individual agents.
RESULTS: For patients with metastatic castratation-resistant prostate cancer, the drug combination of pembrolizumab plus abiraterone and prednisone showed antitumor activity and acceptable safety.
摘要：
目的：醋酸阿比特龙（阿比特龙）加泼尼松被批准用于治疗转移性去势耐药前列腺癌（mCRPC）。我们的目的是评估pembrolizumab联合阿比特龙在mCRPC中的疗效和安全性。
方法：在第1b/2期KEYNOTE-365研究（NCT02861573）的队列D中，患者未接受化疗，筛查前疾病进展≤6个月，并且之前没有接受过用于mCRPC的下一代激素药物,或者之前接受过用于mCRPC的恩杂鲁胺,并且疾病进展或对恩杂鲁胺不耐受.患者每3周静脉注射200mg帕姆单抗，每天一次口服阿比特龙1000mg，每天两次口服泼尼松5mg。主要终点是安全性，前列腺特异性抗原（PSA）反应率，和客观缓解率（ORR）根据实体肿瘤的反应评估标准1.1版（RECISTv1.1）通过盲法独立中心审查（BICR）。次要终点包括根据前列腺癌临床试验第3工作组通过BICR修改的RECISTv1.1的放射学无进展生存期（rPFS）和总生存期（OS）。
■对于接受治疗的103名患者，中位随访时间为28个月（四分位距26-31）。确认的PSA应答率为56%(58/103患者)。RECISTv1.1可测量疾病患者的ORR为16%(6/37患者)。中位rPFS为15个月（95％置信区间9.2-22），中位OS为30个月（95％置信区间23-未达到）；估计的24个月OS率为58％。总的来说,91%的患者经历了治疗相关的不良事件，39%经历过3-5级事件。在12％和6.8％的患者中观察到丙氨酸氨基转移酶（ALT）或天冬氨酸氨基转移酶（AST）的3/4级升高，分别。一名患者因治疗相关的肌无力综合征死亡。研究限制包括单臂设计。
结论：Pembrolizumab联合阿比特龙和泼尼松在未接受化疗的mCRPC患者中显示出抗肿瘤活性和可接受的安全性。3/4级升高的ALT/AST的发生率高于个别药剂的报告。
结果：对于转移性去势抵抗性前列腺癌患者，派姆单抗联合阿比特龙和泼尼松的药物组合显示出抗肿瘤活性和可接受的安全性.
方法：在第1b/2期KEYNOTE-365研究（NCT02861573）的队列D中，患者未接受化疗，筛查前疾病进展≤6个月，并且之前没有接受过用于mCRPC的下一代激素药物,或者之前接受过用于mCRPC的恩杂鲁胺,并且疾病进展或对恩杂鲁胺不耐受.患者每3周静脉注射200mg帕姆单抗，每天一次口服阿比特龙1000mg，每天两次口服泼尼松5mg。主要终点是安全性，前列腺特异性抗原（PSA）反应率，和客观缓解率（ORR）根据实体肿瘤的反应评估标准1.1版（RECISTv1.1）通过盲法独立中心审查（BICR）。次要终点包括根据前列腺癌临床试验第3工作组通过BICR修改的RECISTv1.1的放射学无进展生存期（rPFS）和总生存期（OS）。
■对于接受治疗的103名患者，中位随访时间为28个月（四分位距26-31）。确认的PSA应答率为56%(58/103患者)。RECISTv1.1可测量疾病患者的ORR为16%(6/37患者)。中位rPFS为15个月（95％置信区间9.2-22），中位OS为30个月（95％置信区间23-未达到）；估计的24个月OS率为58％。总的来说,91%的患者经历了治疗相关的不良事件，39%经历过3-5级事件。在12％和6.8％的患者中观察到丙氨酸氨基转移酶（ALT）或天冬氨酸氨基转移酶（AST）的3/4级升高，分别。一名患者因治疗相关的肌无力综合征死亡。研究限制包括单臂设计。
结论：Pembrolizumab联合阿比特龙和泼尼松在未接受化疗的mCRPC患者中显示出抗肿瘤活性和可接受的安全性。3/4级升高的ALT/AST的发生率高于个别药剂的报告。
结果：对于转移性去势抵抗性前列腺癌患者，派姆单抗联合阿比特龙和泼尼松的药物组合显示出抗肿瘤活性和可接受的安全性.
