目的:尽管最近涉及一线免疫检查点抑制剂的试验扩大了晚期尿路上皮癌(aUC)患者的治疗选择,这些患者不适合接受标准的以顺铂为基础的化疗,对于在常规治疗中观察到的患者,试验疗效是否转化为现实世界的有效性,目前证据有限.这项回顾性队列研究比较了KEYNOTE-052试验参与者与接受一线pembrolizumab单药治疗的常规治疗患者之间总生存期(OS)的差异。
方法:使用试验资格标准从FlatironHealth数据库构建常规护理患者队列,并使用匹配调整的间接比较进行加权以平衡EHR和试验患者特征。
结果:常规护理队列年龄较大,更有可能是女性,更常见的是由于肾功能不全导致顺铂不合格。ECOG表现状况在队列之间具有可比性。加权常规护理队列中的中位OS为9个月(95%CI7-16),试验队列中的中位OS为11.3个月(9.7-13.1)。在Kaplan-MeierOS曲线之间没有检测到显著差异(p=0.76)。加权常规护理和试验队列在12-之间的生存概率相似,24-,和36个月(0.45vs.0.47,0.31vs.0.31,0.26vs.分别为0.23)。值得注意的是,与试验参与者相比,常规护理患者在3个月时的生存率略低(0.69vs.分别为0.83)。
结论:我们的结果提供了保证,在常规护理中接受一线免疫治疗的顺铂不合格aUC患者与试验患者的获益相似。
OBJECTIVE: Although recent trials involving first-line immune checkpoint inhibitors have expanded treatment options for patients with advanced urothelial carcinoma (aUC) who are ineligible for standard cisplatin-based chemotherapy, there exists limited evidence for whether
trial efficacy translates into real-world effectiveness for patients seen in routine care. This retrospective cohort
study compares differences in overall survival (OS) between KEYNOTE-052
trial participants and routine-care patients receiving first-line pembrolizumab monotherapy.
METHODS: A routine-care patient cohort was constructed from the Flatiron Health database using
trial eligibility criteria and was weighted to balance EHR and trial patient characteristics using matching-adjusted indirect comparisons.
RESULTS: The routine-care cohort was older, more likely to be female, and more often cisplatin-ineligible due to renal dysfunction. ECOG performance status was comparable between the cohorts. Median OS was 9 months (95% CI 7-16) in the weighted routine-care cohort and 11.3 months (9.7-13.1) in the trial cohort. No significant differences between the Kaplan-Meier OS curves were detected (p = 0.76). Survival probabilities were similar between the weighted routine-care and
trial cohorts at 12-, 24-, and 36- months (0.45 vs. 0.47, 0.31 vs. 0.31, 0.26 vs. 0.23, respectively). Notably, routine care patients had modestly lower survival at 3 months compared to
trial participants (0.69 vs. 0.83, respectively).
CONCLUSIONS: Our results provide reassurance that cisplatin-ineligible aUC patients receiving first-line immunotherapy in routine care experience similar benefits to those observed in trial patients.