Gemcitabine plus Nivolumab with Carboplatin or Oxaliplatin in Cisplatin-Ineligible Patients with Metastatic Urothelial Carcinoma: A Randomized Phase II Trial.

This randomized trial aimed to evaluate gemcitabine/oxaliplatin and gemcitabine/carboplatin, each combined with nivolumab, in cisplatin-ineligible patients with metastatic urothelial carcinoma (mUC).

这项随机试验旨在评估吉西他滨/奥沙利铂和吉西他滨/卡铂，每种药物均与纳武利尤单抗联合使用，在不适合使用顺铂的转移性尿路上皮癌（mUC）患者中的效果。

patients_and_methods

Cisplatin-ineligible patients with mUC were randomized 1:1 to gemcitabine/carboplatin plus nivolumab or gemcitabine/oxaliplatin plus nivolumab for up to 6 cycles, followed by nivolumab monotherapy.

不可接受顺铂治疗的转移性尿路上皮癌（mUC）患者按1:1比例随机分配接受吉西他滨/卡铂加纳武利尤单抗或吉西他滨/奥沙利铂加纳武利尤单抗治疗，最多进行6个周期，之后接受纳武利尤单抗单药治疗。

A pick-the-winner design was employed with objective response rate(ORR) as the primary endpoint.

采用胜者选择设计，以客观缓解率（ORR）作为主要终点。

Secondary endpoints included progression-free survivaland overall survival(OS).

次要终点包括无进展生存期和总生存期（OS）。

Exploratory analyses evaluated plasma protein analytes, circulating immune cell populations, and circulating tumor cells.

探索性分析评估了血浆蛋白分析物、循环免疫细胞群体和循环肿瘤细胞。

Results

Forty-nine patients were enrolled (carboplatin arm, N = 25; oxaliplatin arm, N = 24).

共有49名患者入组（卡铂组，N=25；奥沙利铂组，N=24）。

The ORRs were 69.6% [95% confidence interval(CI), 0.48-0.87] for the carboplatin arm and 33.3% (95% CI, 0.15-0.57) for the oxaliplatin arm.

卡铂组的客观缓解率（ORR）为69.6%（95%置信区间（CI），0.48-0.87），而奥沙利铂组的ORR为33.3%（95% CI，0.15-0.57）。

The median OS rates were 24.74 and 16.43 months for the carboplatin and oxaliplatin arms, respectively (hazard ratio, 1.99; 95% CI, 0.94-4.22; P = 0.07).

卡铂组和奥沙利铂组的中位总生存期分别为24.74个月和16.43个月（风险比，1.99；95% 置信区间，0.94-4.22；P = 0.07）。

Exploratory biomarker analyses revealed sustained adaptive immune activation in the carboplatin arm and features suggestive of tumor-promoting inflammation in the oxaliplatin arm.

探索性生物标志物分析显示，卡铂组持续存在适应性免疫激活，而奥沙利铂组则显示出肿瘤促进性炎症的特征。

Conclusions

Oxaliplatin-based chemoimmunotherapy, versus carboplatin-based chemoimmunotherapy, did not yield a higher response rate, challenging assumptions based on preclinical data.

基于奥沙利铂的化疗免疫治疗与基于卡铂的化疗免疫治疗相比，并没有产生更高的反应率，这挑战了基于临床前数据的假设。