Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles.
Veterans Affairs Health Care System, Durham, NC.
NEJM Evid. 2023 Dec;2(12):EVIDoa2300251. doi: 10.1056/EVIDoa2300251. Epub 2023 Oct 22.
EMBARK, a controlled trial reported elsewhere, showed enzalutamide plus leuprolide (combination) and enzalutamide monotherapy prolonged metastasis-free survival versus placebo plus leuprolide (alone) in patients with high-risk biochemically recurrent prostate cancer. Health-related quality of life was also analyzed but not reported. METHODS: In EMBARK, patients with biochemical recurrence (prostate-specific antigen doubling time of ≤9 months) were randomly assigned (1:1:1) to combination (n=355), leuprolide-alone (n=358), or enzalutamide monotherapy (n=355). In this article we provide the patient-reported outcomes (PROs) from EMBARK at baseline and every 12 weeks until metastasis or death. The key end point was time to first and confirmed clinically meaningful deterioration (TTFD/TTCD) in pain and health-related quality of life using four PRO measures and predefined thresholds. RESULTS: At baseline, all groups had high health-related quality of life. For worst pain, the median TTFD was 19.35 months with leuprolide alone, 13.93 months with combination (hazard ratio, 1.08; 95% confidence interval [CI], 0.89 to 1.30) and 16.59 months with monotherapy (hazard ratio, 1.09; 95% CI, 0.90 to 1.31). The median TTCD was 66.27 months with leuprolide alone, 80.00 months with combination (hazard ratio, 0.82; 95% CI, 0.65 to 1.04), and 60.91 months with monotherapy (hazard ratio, 1.02; 95% CI, 0.82 to 1.28). For Functional Assessment of Cancer Therapy–Prostate total score, the median TTFD was 11.10 months with leuprolide alone, 8.31 months with combination (hazard ratio, 1.14; 95% CI, 0.95 to 1.36), and 8.38 months with monotherapy (hazard ratio, 1.17; 95% CI, 0.98 to 1.39). The median TTCD was 36.53 months with leuprolide alone, 38.77 months with combination (hazard ratio, 1.04; 95% CI, 0.85 to 1.28), and 30.55 months with monotherapy (hazard ratio, 1.16; 95% CI, 0.95 to 1.41). CONCLUSIONS: The PROs from EMBARK show that both enzalutamide combination and monotherapy versus leuprolide alone, with oncologic benefits noted above, preserved high health-related quality of life in patients with high-risk biochemical recurrence of prostate cancer. (Funded by Pfizer and Astellas Pharma; ClinicalTrials.gov number, NCT02319837.)
在其他地方报道的一项对照试验 EM-BARK 显示，与安慰剂联合亮丙瑞林（单用）相比，恩扎卢胺联合亮丙瑞林（联合组）和恩扎卢胺单药治疗（单药组）可延长高危生化复发前列腺癌患者的无转移生存期。同时也分析了与健康相关的生活质量，但并未报告。
在 EM-BARK 中，生化复发（前列腺特异性抗原倍增时间≤9 个月）的患者被随机分为联合组（n=355）、亮丙瑞林单用组（n=358）和恩扎卢胺单药治疗组（n=355）。在本文中，我们提供了 EM-BARK 基线时和每 12 周时的患者报告结局（PRO），直到转移或死亡。主要终点是使用四项 PRO 测量和预设阈值评估疼痛和健康相关生活质量的首次和确认有临床意义的恶化时间（TTFD/TTCD）。
在基线时，所有组的健康相关生活质量都很高。在最严重疼痛方面，亮丙瑞林单用组的中位 TTFD 为 19.35 个月，联合组为 13.93 个月（风险比，1.08；95%置信区间[CI]，0.89 至 1.30），单药组为 16.59 个月（风险比，1.09；95%CI，0.90 至 1.31）。亮丙瑞林单用组的中位 TTCD 为 66.27 个月，联合组为 80.00 个月（风险比，0.82；95%CI，0.65 至 1.04），单药组为 60.91 个月（风险比，1.02；95%CI，0.82 至 1.28）。在功能性癌症治疗评估-前列腺量表总分方面，亮丙瑞林单用组的中位 TTFD 为 11.10 个月，联合组为 8.31 个月（风险比，1.14；95%CI，0.95 至 1.36），单药组为 8.38 个月（风险比，1.17；95%CI，0.98 至 1.39）。亮丙瑞林单用组的中位 TTCD 为 36.53 个月，联合组为 38.77 个月（风险比，1.04；95%CI，0.85 至 1.28），单药组为 30.55 个月（风险比，1.16；95%CI，0.95 至 1.41）。
EM-BARK 的 PRO 结果表明，与亮丙瑞林单用相比，恩扎卢胺联合治疗和单药治疗均保留了高危生化复发前列腺癌患者的高健康相关生活质量，同时也观察到了上述肿瘤学获益。（由辉瑞和安斯泰来制药公司资助；临床试验编号，NCT02319837。）
