Final overall survival and safety analyses of the phase III PSMAfore trial of [177Lu]Lu-PSMA-617 versus change of androgen receptor pathway inhibitor in taxane-naive patients with metastatic castration-resistant prostate cancer.

We report the final overall survival(OS) analysis and updated safety data.

我们报告了最终的总生存（OS）分析和更新的安全性数据。

patients_and_methods

PSMAfore (NCT04689828) was an open-label, international, phase III trial. Patients with prostate-specific membrane antigen (PSMA)-positive mCRPC who had experienced disease progression once on a previous ARPI and were candidates for ARPI change were randomized 1 : 1 to 177Lu-PSMA-617 or ARPI change to abiraterone or enzalutamide.

PSMAfore (NCT04689828) 是一项开放标签、国际性的 III 期试验。对于之前接受过雄激素受体蛋白抑制剂（ARPI）治疗并出现疾病进展的前列腺特异性膜抗原（PSMA）阳性转移性去势抵抗性前列腺癌（mCRPC）患者，如果适合更换 ARPI，将按 1:1 的比例随机分配接受 177Lu-PSMA-617 或更换为阿比特龙或恩杂鲁胺治疗。

Crossover from ARPI change to 177Lu-PSMA-617 was allowed after centrally confirmed radiographic progression.

在中心确认的放射影像学进展后，允许从更换 ARPI 转换为 177Lu-PSMA-617。

Endpoints included rPFS (primary), OS (key secondary), and safety (secondary).

研究终点包括rPFS（主要终点）、OS（关键次要终点）和安全性（次要终点）。

Results

Patients were randomized to 177Lu-PSMA-617 or ARPI change (n = 234 each): 141/234 participants (60.3%) randomized to ARPI change crossed over (75.4% of those with centrally confirmed radiographic progression).

患者被随机分配接受177Lu-PSMA-617治疗或ARPI改变（每组n = 234）：141/234名参与者（60.3%）被随机分配到ARPI改变组后交叉进行了治疗（在中心确认的放射学进展患者中有75.4%进行了交叉治疗）。

The median OS was 24.48 months [95% confidence interval(CI) 19.55-28.94 months] with 177Lu-PSMA-617 versus 23.13 months (95% CI 19.61-25.53 months) with ARPI change [hazard ratio(HR) 0.91, 95% CI 0.72-1.14, P = 0.20] based on the intention-to-treat(ITT) principle; the crossover-adjusted OS HR by inverse probability of censoring weighting modelling was 0.59 (95% CI 0.38-0.91).

基于意向治疗（ITT）原则，使用177Lu-PSMA-617的中位总生存期为24.48个月[95%置信区间（CI）19.55-28.94个月]，而ARPI变化的中位总生存期为23.13个月（95% CI 19.61-25.53个月）[风险比（HR）0.91，95% CI 0.72-1.14，P = 0.20]；通过逆概率加权建模调整交叉后的总生存期HR为0.59（95% CI 0.38-0.91）。

For 177Lu-PSMA-617 versus ARPI change, exposure-adjusted incidences of grade ≥3 and serious treatment-emergent adverse events were 60.8 versus 85.1 and 32.5 versus 49.9 per 100 patient-treatment years, respectively.

对于177Lu-PSMA-617与ARPI变化相比，3级及以上和严重治疗相关不良事件的发生率分别为每100患者-治疗年60.8例和85.1例，以及32.5例和49.9例。

Dry mouth occurred in 135/227 participants (59.5%; 2/227 grade ≥3) and anaemia in 62/227 (27.3%; 14/227 grade ≥3) in the 177Lu-PSMA-617 arm.

在177Lu-PSMA-617组中，227名参与者中有135人（59.5%；227人中有2人3级或以上）出现口干，62人（27.3%；227人中有14人3级或以上）出现贫血。

Conclusions

OS analyses did not show a statistically significant difference between the 177Lu-PSMA-617 and ARPI arms based on the ITT principle; results were likely confounded by the high rate of crossover.

基于意向治疗原则的总生存分析显示，177Lu-PSMA-617组与ARPI组之间没有统计学上的显著差异；由于高比例的交叉，结果可能受到干扰。

The safety profile of 177Lu-PSMA-617 was favourable with no new safety signals identified.

177Lu-PSMA-617的安全性良好，未发现新的安全信号。