ProBio is the first outcome-adaptive platform trial in prostate cancer utilizing a Bayesian framework to evaluate efficacy within predefined biomarker signatures across systemic treatments. Prospective circulating tumor DNA and germline DNA analysis was performed in patients with metastatic castration-resistant prostate cancer before randomization to androgen receptor pathway inhibitors (ARPIs), taxanes or a physician’s choice control arm. The primary endpoint was the time to no longer clinically benefitting (NLCB). Secondary endpoints included overall survival and (serious) adverse events. Upon reaching the time to NLCB, patients could be re-randomized. The primary endpoint was met after 218 randomizations. ARPIs demonstrated ~50% longer time to NLCB compared to taxanes (median, 11.1 versus 6.9 months) and the physician’s choice arm (median, 11.1 versus 7.4 months) in the biomarker-unselected or ‘all’ patient population. ARPIs demonstrated longer overall survival (median, 38.7 versus 21.7 and 21.8 months for taxanes and physician’s choice, respectively). Biomarker signature findings suggest that the largest increase in time to NLCB was observed in AR (single-nucleotide variant/genomic structural rearrangement)-negative and TP53 wild-type patients and TMPRSS2–ERG fusion-positive patients, whereas no difference between ARPIs and taxanes was observed in TP53-altered patients. In summary, ARPIs outperform taxanes and physician’s choice treatment in patients with metastatic castration-resistant prostate cancer with detectable circulating tumor DNA. ClinicalTrials.gov registration: NCT03903835.

ProBio 是首个针对前列腺癌的结果自适应平台试验，利用贝叶斯框架来评估全身治疗中预定义生物标志物特征的疗效。在随机分配到雄激素受体途径抑制剂 （ARPI） 、紫杉烷类药物或医生选择的对照组之前，对转移性去势抵抗性前列腺癌患者进行前瞻性循环肿瘤 DNA 和种系 DNA 分析。主要终点是不再临床受益的时间 （NLCB）。次要终点包括总生存期和（严重）不良事件。达到 NLCB 的时间后，患者可以重新随机分配。在 218 次随机分组后达到主要终点。在生物标志物未选择或“所有”患者群体中，与紫杉烷类药物 （中位数 11.1 个月 vs 6.9 个月） 和医生选择组 （中位数 11.1 个月 vs 7.4 个月） 相比，ARPI 显示 NLCB 的时间长 ~50%。ARPI 显示总生存期更长（紫杉烷类药物和医生选择的中位数分别为 38.7 个月和 21.7 个月和 21.8 个月）。生物标志物特征结果表明，在 AR （单核苷酸变异/基因组结构重排） 阴性和 TP53 野生型患者以及 TMPRSS2-ERG 融合阳性患者中观察到 NLCB 时间的增加最大，而在 TP53 改变的患者中未观察到 ARPI 和紫杉烷类药物之间的差异。总之，ARPI 在可检测到循环肿瘤 DNA 的转移性去势抵抗性前列腺癌患者中优于紫杉烷类和医生选择治疗。ClinicalTrials.gov 注册：NCT03903835。