Enfortumab vedotin (EV) 联合派姆单抗相比于化疗第一线治疗局部晚期转移性尿路上皮癌 (12/24/2023)
Enfortumab vedotin in combination with pembrolizumab vs chemotherapy for untreated locally advanced metastatic urothelial carcinoma
这是一项全球性 III 期, 开放标签, 随机研究(EV-302/KEYNOTE-A39), 评估先前未经治疗的局部晚期转移性尿路上皮癌患者（有资格接受含顺铂或卡铂化疗的患者）。
方法: 患者（无论 PD-L1 表达情况）按 1:1 随机分配，接受每 3 周的第 1 天和第 8 天 EV（1.25 mg/kg；静脉）, 每 3 周的第 1 天派姆单抗（P, pembroliumab, 200 mg；静脉）l 或吉西他滨联合顺铂或卡铂。双重主要终点是无进展生存期和总生存期。次要终点包括总体响应率和安全性。
结果: 886 名患者（EV+P：442；化疗：444）被随机分组。 数据截止时, 中位随访时间为 17.2 个月。 与化疗相比, EV+P 的无进展生存期显著延长, 进展或死亡风险降低了 55%（中位无进展生存期分别为 12.5 个月相比于6.3 个月; HR 0.45 [95% CI: 0.38-0.54]；P <0.00001）。 与化疗相比, EV+P 的总生存期显著延长, 死亡风险降低了 53%（中位总生存期分别为 31.5 个月相比于16.1 个月; HR 0.47 [95% CI; 0.38-0.58]; P <0.00001）。 EV+P 组和化疗组的确认总体响应率分别为 67.7% 和 44.4%（P <0.00001）。
EV+P 组中 55.9% 发生 3 级以上 治疗相关的不良反应相比于化疗组中的 69.5% 。最常见的是 EV+P 中的斑丘疹 (7.7%)、高血糖 (5.0%) 和中性粒细胞减少症 (4.8%)，以及化疗中的贫血 (31.4%)、中性粒细胞减少症 (30.0%) 和血小板减少症 (19.4%)。 对 EV 最常见（≥5%）≥3 级治疗相关的不良反应包括皮肤反应（15.5%）、周围神经病变（6.8%）和高血糖（6.1%）。派姆单抗最常见 (≥5%) ≥3 级的不良反应包括严重皮肤反应 (11.8%)。
结论: EV+P 显著改善了先前未经治疗的局部晚期转移性尿路上皮癌患者的预后, 与化疗相比, 中位无进展生存期和总生存期几乎翻倍。 安全状况总体上是可控的，没有新的安全信号。 这些结果支持 EV+P 作为局部晚期转移性尿路上皮癌的新第一线治疗。
This is a global phase III, open-label, randomized study (EV-302/KEYNOTE-A39) evaluating patients with previously untreated locally advanced metastatic urothelial carcinoma who were eligible to receive cisplatin- or carboplatin-containing chemotherapy. patients.
Methods: Patients (regardless of PD-L1 expression) were randomly assigned 1:1 to receive EV (1.25 mg/kg; intravenously) on day 1 and 8 every 3 weeks, and pembrolizumab (P, pembrolizumab, 200 mg; intravenously) on day 1 of every 3 week cycle, vs chemotherapy (gemcitabine plus cisplatin or carboplatin). The dual primary endpoints were progression-free survival and overall survival. Secondary endpoints included overall response rate and safety.
Results: 886 patients (EV+P: 442; chemotherapy: 444) were randomized. At data cutoff, the median follow-up time was 17.2 months. Compared with chemotherapy, EV+P was associated with significantly longer progression-free survival and a 55% lower risk of progression or death (median progression-free survival, 12.5 months vs. 6.3 months, respectively; HR 0.45 [95% CI: 0.38-0.54]; P <0.00001). Compared with chemotherapy, EV+P resulted in significantly longer overall survival and a 53% lower risk of death (median overall survival, 31.5 months vs. 16.1 months; HR 0.47 [95% CI; 0.38-0.58]; P <0.00001). The confirmed overall response rates were 67.7% in the EV+P group and 44.4% in the chemotherapy group (P<0.00001).
Grade 3 or higher treatment-related adverse effects occurred in 55.9% of the EV+P group compared with 69.5% of the chemotherapy group. The most common were maculopapular rash (7.7%), hyperglycemia (5.0%), and neutropenia (4.8%) in EV+P group, and anemia (31.4%), neutropenia in chemotherapy group (30.0%) and thrombocytopenia (19.4%). The most common (≥5%) grade ≥3 treatment-related adverse effects in EV group included skin reactions (15.5%), peripheral neuropathy (6.8%), and hyperglycemia (6.1%). The most common (≥5%) grade ≥3 adverse effects with pembrolizumab included serious skin reactions (11.8%).
Conclusions: EV+P significantly improved outcome in patients with previously untreated locally advanced metastatic urothelial carcinoma, nearly doubling median progression-free survival and overall survival compared with chemotherapy. The safety prolife was generally controllable and there were no new security signals. These results support EV+P as a new first-line standard of care for locally advanced metastatic urothelial carcinoma.
参考文献 Reference
Powles TB et al. Annals of Oncol 2023: 34 (suppl_2)