Perioperative Apalutamide in High-Risk Localized Prostate Cancer.

Methods

We conducted a phase 3, double-blind, placebo-controlledtrial in which patients with newly diagnosed high-risk localized or locally advanced prostate cancer were randomly assigned in a 1:1 ratio to receive androgen-deprivation therapy (ADT) plus apalutamide (240 mg per day) or ADT plus placebo for 6 cycles (28 days each) before and after radical prostatectomy with pelvic lymph-node dissection.

我们进行了一项III期、双盲、安慰剂对照试验，其中新诊断的高风险局限性或局部晚期前列腺癌患者按1:1的比例随机分配接受雄激素剥夺治疗（ADT）加阿帕鲁他胺（每天240毫克）或ADT加安慰剂治疗，每6个周期（每个周期28天），在根治性前列腺切除术及盆腔淋巴结清扫术前后进行。

The dual primary end points were a composite of pathological complete response or minimal residual disease (defined as a pathological stage of ypT2 or lower, with a tumor size of ≤5 mm in the greatest dimension) and metastasis-free survival, as assessed with conventional imaging or prostate-specific membrane antigen positron-emission tomography.

主要终点是病理完全缓解或最小残留疾病（定义为病理分期ypT2或更低，肿瘤最大尺寸≤5毫米）的复合终点，以及通过常规影像学或前列腺特异性膜抗原正电子发射断层扫描评估的无转移生存期。

Secondary end points included event-free survival, first subsequent treatment, and distant metastasis (assessed in time-to-event analyses), as well as safety.

次要终点包括无事件生存期、首次后续治疗和远处转移（在时间至事件分析中评估），以及安全性。

Results

A total of 2109 patients underwent randomization: 1057 were assigned to receive ADT plus apalutamide, and 1052 to receive ADT plus placebo.

共有2109名患者进行了随机分组：1057名被分配接受雄激素剥夺治疗（ADT）加阿帕鲁替胺治疗，1052名被分配接受ADT加安慰剂治疗。

The median follow-up was 61.7 months.

中位随访时间为61.7个月。

The percentage of patients with a pathological complete response or minimal residual disease was significantly higher in the apalutamide group than in the placebo group (8.9% vs. 1.0%; odds ratio, 10.17; 95% confidence interval[CI], 5.27 to 19.64; P<0.001), as was the percentage of patients with metastasis-free survival (probability of metastasis-free survival at 5 years, 78.2% vs. 73.5%; hazard ratiofor distant metastasis or death, 0.80; 95% CI, 0.67 to 0.96; P = 0.02).

在阿帕他胺组中，病理完全缓解或微小残留疾病的患者百分比显著高于安慰剂组（8.9%对比1.0%；比值比，10.17；95%置信区间[CI]，5.27至19.64；P<0.001），无转移生存的患者百分比也是如此（5年无转移生存的概率，78.2%对比73.5%；远处转移或死亡的风险比，0.80；95% CI，0.67至0.96；P = 0.02）。

Event-free survival, time to the first subsequent treatment, and time to distant metastasis significantly favored ADT plus apalutamide over ADT plus placebo (P<0.001 for all between-group comparisons).

无事件生存期、首次后续治疗时间和远处转移时间显著偏向于ADT加阿帕他胺组，与ADT加安慰剂组相比（所有组间比较P<0.001）。

Grade 3 or 4 adverse events occurred in 39.6% of the patients in the apalutamide group and in 31.0% of those in the placebo group, with the difference between the groups driven primarily by a higher incidenceof rash in the apalutamide group.

在阿帕他胺组的患者中，39.6%的患者出现了3级或4级的不良事件，在安慰剂组的患者中这一比例为31.0%，两组之间的差异主要由阿帕他胺组更高的皮疹发生率所驱动。

Conclusions

Perioperative treatment with ADT plus apalutamide was associated with better oncologic outcomes of radical prostatectomy in patients with high-risk localized or locally advanced prostate cancer than treatment with ADT plus placebo.

与接受ADT加安慰剂治疗的患者相比，接受ADT加阿帕他胺的围手术期治疗与高风险局部或局部晚期前列腺癌患者的根治性前列腺切除术的更好的肿瘤学结果相关。

Adverse events were more common in the apalutamide group than in the placebo group.

不良事件在阿帕他胺组比安慰剂组更为常见。

(Funded by Johnson & Johnson; PROTEUS ClinicalTrials.gov number, NCT03767244.).

(由强生公司资助；PROTEUS临床试验注册号，NCT03767244。)