Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA.
Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Eur Urol. 2019 Oct;76(4):524-532. doi: 10.1016/j.eururo.2019.07.032. Epub 2019 Jul 28.
Limited data compare first-line carboplatin-based chemotherapy and immune checkpoint blockade in cisplatin-ineligible metastatic urothelial carcinoma (mUC) patients. The primary evidence guiding treatment decisions was a recent Food and Drug Administration/European Medicines Agency safety alert based on emerging data from two ongoing phase III trials, reporting shorter survival in programmed death-ligand 1 (PD-L1)-negative patients receiving immunotherapy. Final results from these trials are unknown.
To compare survival in cisplatin-ineligible mUC patients receiving first-line immunotherapy versus those receiving carboplatin-based chemotherapy.
DESIGN, SETTING, AND PARTICIPANTS: We conducted a retrospective cohort study of 2017 mUC patients receiving first-line carboplatin-based chemotherapy (n = 1530) or immunotherapy (n = 487) from January 1, 2011 to May 18, 2018 using the Flatiron Health electronic health record-derived database.
The primary outcomes were overall survival (OS), comparing 12- and 36-mo OS, and hazard ratios before and after 12 mo. Propensity score-based inverse probability of treatment weighting (IPTW) was used to address confounding in Kaplan-Meier and Cox regression model estimates of comparative effectiveness.
IPTW-adjusted OS rates in the immunotherapy group were lower at 12 mo (39.6% [95% confidence interval {CI} 34.0-45.3%] vs 46.1% [95% CI 43.4-48.8%]) but higher at 36 mo (28.3% [95% CI 21.8-34.7%] vs 13.3% [95% CI 11.1-15.5%]) relative to the chemotherapy group. Immunotherapy treatment demonstrated inferior OS during the first 12 mo relative to carboplatin-based chemotherapy (IPTW-adjusted hazard ratio [HR] 1.37, 95% CI 1.15-1.62), but superior OS beyond 12 mo (IPTW-adjusted HR 0.50, 95% CI 0.30-0.85). Limitations include retrospective design and potential unmeasured confounding.
In the setting of mUC, clinicians and patients should carefully consider how to balance the short-term benefit of chemotherapy against the long-term benefit of immunotherapy.
To determine the optimal first-line therapy for metastatic bladder cancer patients who are unfit for cisplatin, we compared carboplatin-based chemotherapy versus immunotherapy using real-world data. Survival in the 1st year of treatment was lower with immunotherapy relative to chemotherapy, but for patients surviving beyond the 1st year, immunotherapy was superior.
有限的数据比较了一线含卡铂化疗与免疫检查点阻断在不适合顺铂的转移性尿路上皮癌（mUC）患者中的疗效。指导治疗决策的主要证据是最近的美国食品和药物管理局/欧洲药品管理局的一项安全警报，该警报基于两项正在进行的 III 期试验的新数据，报告称在接受免疫治疗的 PD-L1 阴性患者中，生存时间更短。这些试验的最终结果尚不清楚。
比较不适合顺铂的 mUC 患者接受一线免疫治疗与接受含卡铂化疗的患者的生存情况。
设计、地点和参与者：我们使用 Flatiron Health 电子病历数据库进行了一项回顾性队列研究，纳入了 2011 年 1 月 1 日至 2018 年 5 月 18 日期间接受一线含卡铂化疗（n=1530）或免疫治疗（n=487）的 2017 例 mUC 患者。
主要结局是总生存期（OS），比较 12 个月和 36 个月的 OS 以及 12 个月前后的危险比。采用倾向评分逆概率治疗加权（IPTW）来解决 Kaplan-Meier 和 Cox 回归模型中比较有效性的混杂因素。
免疫治疗组的 12 个月时的 OS 率较低（39.6% [95%置信区间 {CI} 34.0-45.3%] vs. 46.1% [95% CI 43.4-48.8%]），但 36 个月时的 OS 率较高（28.3% [95% CI 21.8-34.7%] vs. 13.3% [95% CI 11.1-15.5%]）。与化疗组相比，免疫治疗在最初 12 个月的 OS 较差（IPTW 调整后的危险比 [HR] 1.37，95% CI 1.15-1.62），但在 12 个月后 OS 更好（IPTW 调整后的 HR 0.50，95% CI 0.30-0.85）。局限性包括回顾性设计和潜在的无法测量的混杂因素。
在 mUC 中，临床医生和患者应仔细考虑如何平衡化疗的短期益处与免疫治疗的长期益处。
为了确定不适合顺铂的转移性膀胱癌患者的最佳一线治疗方法，我们使用真实世界的数据比较了卡铂化疗与免疫治疗。与化疗相比，免疫治疗在治疗的第 1 年的生存率较低，但对于第 1 年以后存活的患者，免疫治疗的效果更好。
