Department of Radiation Oncology & Molecular Radiation Sciences, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD.
Department of Medical Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD.
J Clin Oncol. 2023 Feb 20;41(6):1307-1317. doi: 10.1200/JCO.22.01662. Epub 2022 Nov 11.
We sought to investigate whether enzalutamide (ENZA), without concurrent androgen deprivation therapy, increases freedom from prostate-specific antigen (PSA) progression (FFPP) when combined with salvage radiation therapy (SRT) in men with recurrent prostate cancer after radical prostatectomy (RP).
Men with biochemically recurrent prostate cancer after RP were enrolled into a randomized, double-blind, phase II, placebo-controlled, multicenter study of SRT plus ENZA or placebo (ClinicalTrials.gov identifier: NCT02203695). Random assignment (1:1) was stratified by center, surgical margin status (R0 R1), PSA before salvage treatment (PSA ≥ 0.5 < 0.5 ng/mL), and pathologic Gleason sum (7 8-10). Patients were assigned to receive either ENZA 160 mg once daily or matching placebo for 6 months. After 2 months of study drug therapy, external-beam radiation (66.6-70.2 Gy) was administered to the prostate bed (no pelvic nodes). The primary end point was FFPP in the intention-to-treat population. Secondary end points were time to local recurrence within the radiation field, metastasis-free survival, and safety as determined by frequency and severity of adverse events.
Eighty-six (86) patients were randomly assigned, with a median follow-up of 34 (range, 0-52) months. Trial arms were well balanced. The median pre-SRT PSA was 0.3 (range, 0.06-4.6) ng/mL, 56 of 86 patients (65%) had extraprostatic disease (pT3), 39 of 86 (45%) had a Gleason sum of 8-10, and 43 of 86 (50%) had positive surgical margins (R1). FFPP was significantly improved with ENZA versus placebo (hazard ratio [HR], 0.42; 95% CI, 0.19 to 0.92; = .031), and 2-year FFPP was 84% versus 66%, respectively. Subgroup analyses demonstrated differential benefit of ENZA in men with pT3 (HR, 0.22; 95% CI, 0.07 to 0.69) versus pT2 disease (HR, 1.54; 95% CI, 0.43 to 5.47; = .019) and R1 (HR, 0.14; 95% CI, 0.03 to 0.64) versus R0 disease (HR, 1.00; 95% CI, 0.36 to 2.76; = .023). There were insufficient secondary end point events for analysis. The most common adverse events were grade 1-2 fatigue (65% ENZA 53% placebo) and urinary frequency (40% ENZA 49% placebo).
SRT plus ENZA monotherapy for 6 months in men with PSA-recurrent high-risk prostate cancer after RP is safe and delays PSA progression relative to SRT alone. The impact of ENZA on distant metastasis or survival is unknown at this time.
我们旨在探讨在根治性前列腺切除术（RP）后发生生化复发的前列腺癌患者中，与安慰剂相比，在挽救性放疗（SRT）的基础上加用恩扎卢胺（ENZA）是否能提高前列腺特异性抗原（PSA）无进展（FFPP）率。
在一项随机、双盲、二期、安慰剂对照、多中心的 SRT 联合 ENZA 或安慰剂治疗复发性前列腺癌的研究（ClinicalTrials.gov 标识符：NCT02203695）中，我们招募了 RP 后生化复发的男性患者。按照 1:1 的比例进行随机分组，分层因素为中心、手术切缘状态（R0 或 R1）、挽救性治疗前 PSA（PSA≥0.5 或 <0.5ng/mL）和病理 Gleason 评分总和（7 或 8-10）。患者被分配接受每日 160mg 的 ENZA 或匹配的安慰剂治疗 6 个月。在研究药物治疗 2 个月后，给予前列腺床外照射（66.6-70.2Gy）（无盆腔淋巴结照射）。主要终点是意向治疗人群中的 FFPP。次要终点是放疗野内局部复发时间、无转移生存以及根据不良事件的频率和严重程度确定的安全性。
86 例患者被随机分配，中位随访时间为 34 个月（范围：0-52 个月）。试验臂之间平衡良好。中位 SRT 前 PSA 为 0.3ng/mL（范围：0.06-4.6ng/mL），86 例患者中有 56 例（65%）有前列腺外疾病（pT3），39 例（45%）有 8-10 分的 Gleason 评分，43 例（50%）有阳性手术切缘（R1）。与安慰剂相比，ENZA 显著改善了 FFPP（风险比[HR]，0.42；95%置信区间，0.19 至 0.92；=0.031），2 年 FFPP 分别为 84%和 66%。亚组分析表明，ENZA 在 pT3 患者（HR，0.22；95%置信区间，0.07 至 0.69）中获益优于 pT2 疾病（HR，1.54；95%置信区间，0.43 至 5.47；=0.019）和 R1 患者（HR，0.14；95%置信区间，0.03 至 0.64；=0.023）中具有差异。次要终点事件的发生率不足，无法进行分析。最常见的不良反应是 1-2 级疲劳（ENZA 组 65%，安慰剂组 53%）和尿频（ENZA 组 40%，安慰剂组 49%）。
在 RP 后发生 PSA 复发性高危前列腺癌的男性中，SRT 联合恩扎卢胺（ENZA）单药治疗 6 个月是安全的，与单独 SRT 相比可延迟 PSA 进展。目前尚不清楚恩扎卢胺（ENZA）对远处转移或生存的影响。
