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Abstract：
BACKGROUND: Immune checkpoint inhibitors have changed previous treatment paradigm of advanced urothelial carcinoma (UC). The ARON-2 study (NCT05290038) aimed to assess the real-world effectiveness of pembrolizumab in patients recurred or progressed after platinum-based chemotherapy.
METHODS: Medical records of patients with documented metastatic UC treated by pembrolizumab as second-line therapy were retrospectively collected from 88 institutions in 23 countries. Patients were assessed for overall survival (OS), progression-free survival (PFS) and overall response rate (ORR). Cox proportional hazards models were adopted to explore the presence of prognostic factors.
RESULTS: In total, 836 patients were included: 544 patients (65%) received pembrolizumab after progression to first-line platinum-based chemotherapy in the metastatic setting (cohort A) and 292 (35%) after recurring within < 12 months since the completion of adjuvant or neoadjuvant chemotherapy (cohort B). The median follow-up time was 15.3 months. The median OS and the ORR were 10.5 months and 31% in the overall study population, 9.1 months and 29% in cohort A and 14.6 months and 37% in cohort B. At multivariate analysis, ECOG-PS ≥ 2, bone metastases, liver metastases and pembrolizumab setting (cohort A vs B) proved to be significantly associated with worst OS and PFS. Stratified by the presence of 0, 1-2 or 3-4 prognostic factors, the median OS was 29.4, 12.5 and 4.1 months (p < 0.001), while the median PFS was 12.2, 6.4 and 2.8 months, respectively (p < 0.001).
CONCLUSIONS: Our study confirms that pembrolizumab is effective in the advanced UC real-world context, showing outcome differences between patients recurred or progressed after platinum-based chemotherapy.
METHODS: Medical records of patients with documented metastatic UC treated by pembrolizumab as second-line therapy were retrospectively collected from 88 institutions in 23 countries. Patients were assessed for overall survival (OS), progression-free survival (PFS) and overall response rate (ORR). Cox proportional hazards models were adopted to explore the presence of prognostic factors.
RESULTS: In total, 836 patients were included: 544 patients (65%) received pembrolizumab after progression to first-line platinum-based chemotherapy in the metastatic setting (cohort A) and 292 (35%) after recurring within < 12 months since the completion of adjuvant or neoadjuvant chemotherapy (cohort B). The median follow-up time was 15.3 months. The median OS and the ORR were 10.5 months and 31% in the overall study population, 9.1 months and 29% in cohort A and 14.6 months and 37% in cohort B. At multivariate analysis, ECOG-PS ≥ 2, bone metastases, liver metastases and pembrolizumab setting (cohort A vs B) proved to be significantly associated with worst OS and PFS. Stratified by the presence of 0, 1-2 or 3-4 prognostic factors, the median OS was 29.4, 12.5 and 4.1 months (p < 0.001), while the median PFS was 12.2, 6.4 and 2.8 months, respectively (p < 0.001).
CONCLUSIONS: Our study confirms that pembrolizumab is effective in the advanced UC real-world context, showing outcome differences between patients recurred or progressed after platinum-based chemotherapy.
摘要：
背景：免疫检查点抑制剂改变了以前晚期尿路上皮癌（UC）的治疗模式。ARON-2研究（NCT05290038）旨在评估pembrolizumab在铂类化疗后复发或进展患者中的真实世界有效性。
方法：回顾性收集了23个国家的88个机构中记录的接受pembrolizumab作为二线治疗的转移性UC患者的病历。评估患者的总生存期（OS），无进展生存期（PFS）和总缓解率（ORR）。采用Cox比例风险模型来探讨预后因素的存在。
结果：总计，包括836例患者：544例患者（65%）在转移情况下进展为一线铂类化疗后接受派姆单抗（队列A），在辅助或新辅助化疗完成后<12个月内复发后接受292例患者（35%）。中位随访时间为15.3个月。在整个研究人群中，中位OS和ORR分别为10.5个月和31%，队列A为9.1个月和29％，队列B为14.6个月和37％。在多变量分析中，ECOG-PS≥2，骨转移，肝转移和pembrolizumab设置(队列AvsB)被证明与最差OS和PFS显著相关.通过存在0、1-2或3-4个预后因素进行分层，中位OS分别为29.4、12.5和4.1个月(p<0.001)，而中位PFS为12.2、6.4和2.8个月，分别(p<0.001)。
结论：我们的研究证实，pembrolizumab在先进的UC真实世界环境中是有效的，显示铂类化疗后复发或进展患者之间的结局差异。
方法：回顾性收集了23个国家的88个机构中记录的接受pembrolizumab作为二线治疗的转移性UC患者的病历。评估患者的总生存期（OS），无进展生存期（PFS）和总缓解率（ORR）。采用Cox比例风险模型来探讨预后因素的存在。
结果：总计，包括836例患者：544例患者（65%）在转移情况下进展为一线铂类化疗后接受派姆单抗（队列A），在辅助或新辅助化疗完成后<12个月内复发后接受292例患者（35%）。中位随访时间为15.3个月。在整个研究人群中，中位OS和ORR分别为10.5个月和31%，队列A为9.1个月和29％，队列B为14.6个月和37％。在多变量分析中，ECOG-PS≥2，骨转移，肝转移和pembrolizumab设置(队列AvsB)被证明与最差OS和PFS显著相关.通过存在0、1-2或3-4个预后因素进行分层，中位OS分别为29.4、12.5和4.1个月(p<0.001)，而中位PFS为12.2、6.4和2.8个月，分别(p<0.001)。
结论：我们的研究证实，pembrolizumab在先进的UC真实世界环境中是有效的，显示铂类化疗后复发或进展患者之间的结局差异。
