Three versus six cycles of platinum-based chemotherapy followed by avelumab maintenance as first-line treatment for advanced urothelial cancer: the phase II DISCUS trial.

To investigate whether shorter chemotherapy duration improves quality of life (QoL) without worsening efficacy, this study compared three versus six cycles followed by avelumab.

为了调查较短化疗疗程是否能在不降低疗效的情况下改善生活质量（QoL），本研究比较了三个周期与六个周期化疗后继以avelumab的疗效。

patients_and_methods

This randomized phase II trial compared three versus six cycles (3C arm versus 6C arm) of chemotherapy followed by avelumab in patients receiving first-line treatment for mUC.

这项随机II期试验比较了接受mUC一线治疗的患者在化疗后使用avelumab，对比了三周期（3C组）与六周期（6C组）的疗效。

This trial had co-primary endpoints of patient-reported outcomes (PROs), defined as change from baseline to cycle 6 on the global health status/QoL score, and superior overall survival(OS).

该试验的主要终点是患者报告的结果（PROs），定义为从基线到第6周期的全球健康状况/生活质量评分的变化，以及更优越的总生存（OS）。

Secondary endpoints included progression-free survival(PFS), overall response rate, and safety.

次要终点包括无进展生存期（PFS）、总缓解率和安全性。

Here, we report the final PRO analysis and interim OS.

在这里，我们报告了最终的患者报告结果（PRO）分析和中期总生存（OS）数据。

Results

A total of 267 patients were randomized (133 to 3C arm, 134 to 6C arm).

共有267名患者被随机分配（133名进入3C组，134名进入6C组）。

Forty-two percent received gemcitabine/cisplatin and 58% gemcitabine/carboplatin.

42%的患者接受了吉西他滨/顺铂治疗，而58%的患者接受了吉西他滨/卡铂治疗。

Seventy-eight percent and 40% of patients completed three and six cycles as allocated.

78%和40%的患者完成了按计划分配的三个和六个周期。

Seventy-four percent of patients received avelumab in the 3C arm, versus 56% in the 6C arm.

在3C组中，74%的患者接受了avelumab治疗，而在6C组中这一比例为56%。

The mean QoL change between baseline and cycle 6 was 0 [95% confidence interval(CI) -5.9 to 5.2] in the 3C arm versus -8.5 (95% CI -14.1 to -2.9) in the 6C arm, with a significant difference favouring 3C (+8.5 points, 95% CI 0.7-16.3, P = 0.016).

基线与第6周期之间的平均生活质量变化在3C组为0 [95%置信区间（CI）-5.9至5.2]，而在6C组为-8.5（95% CI -14.1至-2.9），3C组显著优于6C组（+8.5分，95% CI 0.7-16.3，P = 0.016）。

Improvement in PRO scores was observed in 41% (3C arm) versus 24% (6C arm) of patients.

在3C组中有41%的患者观察到PRO评分有所改善，而在6C组中这一比例为24%。

OS was not significant (18.9 months in both arms [hazard ratio(HR) 1.15, 95% CI 0.72-1.86, P = 0.56].

总生存期无显著差异（两组均为18.9个月[风险比（HR）1.15，95%置信区间0.72-1.86，P=0.56]）。

Median PFS was 8.0 months (95% CI 6.7-11.9 months) in the 3C arm versus 9.0 months (95% CI 6.9-12.7 months) in the 6C arm (HR 1.05, 95% CI 0.73-1.53).

中位无进展生存期（PFS）在3C组为8.0个月（95%置信区间6.7-11.9个月），而在6C组为9.0个月（95%置信区间6.9-12.7个月）（HR 1.05，95%置信区间0.73-1.53）。

Median grade 3-4 treatment-related adverse events occurred in 11.9% (3C arm) versus 15.7% (6C arm).

3级或4级治疗相关不良事件的发生率为11.9%（3C组）对比15.7%（6C组）。

Conclusions

Three cycles of chemotherapy followed by maintenance avelumab is associated with better QoL than six cycles.

接受三周期化疗后进行avelumab维持治疗的患者，其生活质量（QoL）优于接受六周期化疗的患者。

Randomized trials with patient-focused outcomes exploring shorter duration of therapy are feasible (NCT06892860).

探索较短治疗持续时间的以患者为中心结果的随机试验是可行的（NCT06892860）。