Accelerating Drug Development in Hormone-Naïve Prostate Cancer through Multimodal Therapy Strategies: The MetaCURE Phase 2 Randomized Clinical Trial.

patients_and_methods

In the MetaCURE trial, patients with untreated, high-risk localized (cohort A) or low-volume metastatic (cohort B) disease were randomized 1:1 to apalutamide or apalutamide and abiraterone acetate plus prednisone and androgen deprivation therapy for 10 months.

在MetaCURE试验中，未接受治疗的高风险局部（队列A）或低体积转移性（队列B）疾病的患者被随机分为1:1，接受阿帕鲁他胺或阿帕鲁他胺和阿比特龙醋酸酯加泼尼松以及雄激素剥夺治疗10个月。

Cohort B also received stereotactic body radiotherapy (RT) at 4 months.

B队列也在4个月时接受了立体定向体部放射治疗(RT)。

All patients underwent a radical prostatectomy (6 months ± postoperative RT at 10 months).

所有患者均接受了根治性前列腺切除术（术后10个月时可进行放疗±6个月）。

The primary endpoint was pathologic complete response (pCR; no residual tumor) or minimal residual disease (MRD; ≤5 mm residual carcinoma), and the secondary endpoint an undetectable PSA following testosterone (T) recovery (T ≥ 150 ng/dL) at 24 months.

主要终点是病理完全缓解（pCR；无残留肿瘤）或最小残留疾病（MRD；≤5毫米残留癌），次要终点是在24个月时，睾酮（T）恢复（T ≥ 150 ng/dL）后PSA无法检测到。

Results

A pCR or MRD was achieved in 4 [12%; 90% confidence interval(CI), 4%-26%] and 5 (15%; 90% CI, 6%-29%) patients in cohorts A and B, respectively.

在A和B队列中，分别有4名（12%；90%置信区间（CI），4%-26%）和5名（15%；90% CI，6%-29%）患者实现了pCR或MRD。

Undetectable PSA and T-recovery at 24 months occurred in 20 (61%; 95% CI, 42%-77%) patients in cohort A and 13 (39%; 95% CI, 23%-58%) patients in cohort B.

在A队列中，24个月时PSA不可检测和T细胞恢复发生在20名患者中（61%；95%置信区间，42%-77%），而在B队列中，这一情况发生在13名患者中（39%；95%置信区间，23%-58%）。

Conclusions

MMT for newly diagnosed high-risk localized and low-volume metastatic prostate cancer is feasible, safe, and provides a rapid readout of efficacy.

对于新诊断的高危局部和低体积转移性前列腺癌，MMT是可行的、安全的，并且可以快速提供疗效反馈。

A significant proportion of patients, including those with oligometastatic disease, maintained an undetectable PSA following T-recovery at the 2-year endpoint.

包括寡转移性疾病患者在内，相当比例的患者在T细胞恢复后的2年终点时，前列腺特异性抗原（PSA）维持在无法检测的水平。

These results have informed the design of an adaptive trial using MMT on a continuous basis to prioritize effective approaches for further study.

这些结果为设计一项使用多模式治疗（MMT）进行连续性治疗的自适应试验提供了依据，以优先考虑进一步研究的有效方法。