Enfortumab Vedotin and Pembrolizumab in Cisplatin-Eligible Bladder Cancer.

The efficacy and safety of neoadjuvant and adjuvant (perioperative) enfortumab vedotin-pembrolizumab as compared with neoadjuvant cisplatin-based chemotherapy in persons with this cancer are unclear.

与新辅助顺铂为基础的化疗相比，新辅助和辅助（围手术期）enfortumab vedotin-pembrolizumab的疗效和安全性在患有此癌症的人群中尚不明确。

Methods

We conducted a phase 3, open-label, randomized trial involving adults with muscle-invasive bladder cancer eligible for cisplatin-based chemotherapy and radical cystectomy with pelvic lymph-node dissection (cystectomy).

我们进行了一项III期、开放标签、随机试验，涉及符合顺铂为基础的化疗和根治性膀胱切除术加盆腔淋巴结清扫术（膀胱切除术）的肌肉浸润性膀胱癌成人患者。

Participants were assigned to receive neoadjuvant enfortumab vedotin-pembrolizumab (4 cycles; enfortumab vedotin [1.25 mg per kilogram of body weight on days 1 and 8] and pembrolizumab [200 mg on day 1] every 3 weeks), cystectomy, and 5 cycles of enfortumab vedotin and 13 cycles of pembrolizumab as adjuvant therapy or to receive neoadjuvant cisplatin-gemcitabine (4 cycles; cisplatin [70 mg per square meter of body-surface area on day 1] plus gemcitabine [1000 mg per square meter on days 1 and 8] every 3 weeks) and cystectomy.

参与者被分配接受新辅助恩福替尼韦多替尼-帕博利珠单抗（4个周期；恩福替尼韦多替尼[每公斤体重1.25毫克，第1天和第8天]和帕博利珠单抗[第1天200毫克]，每3周一次），膀胱切除术，以及作为辅助治疗的5个周期恩福替尼韦多替尼和13个周期帕博利珠单抗，或者接受新辅助顺铂-吉西他滨（4个周期；顺铂[第1天每平方米体表面积70毫克]加吉西他滨[第1天和第8天每平方米1000毫克]，每3周一次）和膀胱切除术。

The primary end point was event-free survival; key secondary end points were overall survivaland pathological complete response.

主要终点是无事件生存期；关键次要终点是总生存和病理完全缓解。

Safety was assessed.

安全性得到了评估。

Results

A total of 405 participants were assigned to receive enfortumab vedotin-pembrolizumab and 403 to receive cisplatin-gemcitabine.

共有405名参与者被分配接受恩福妥单抗-维多珠单抗治疗，403名被分配接受顺铂-吉西他滨治疗。

The median time from randomization to the data-cutoff date was 33.6 months (range, 22.5 to 53.6).

从随机分组到数据截止日期的中位时间是33.6个月（范围，22.5至53.6个月）。

A total of 86.7% of the participants in the enfortumab vedotin-pembrolizumab group and 89.6% of those in the cisplatin-gemcitabine group underwent cystectomy.

在恩福他木单抗-帕博利珠单抗组中，86.7% 的参与者和在顺铂-吉西他滨组中的 89.6% 接受了膀胱切除术。

At 2 years, estimated event-free survival was 79.4% with enfortumab vedotin-pembrolizumab and 66.2% with cisplatin-gemcitabine (hazard ratiofor an event or death, 0.53; 95% confidence interval[CI], 0.41 to 0.70; P<0.001); estimated overall survivalwas 86.9% and 81.3%, respectively (hazard ratiofor death, 0.65; 95% CI, 0.48 to 0.89; two-sided P = 0.006).

在 2 年时，恩福他木单抗-帕博利珠单抗的无事件生存率估计为 79.4%，而顺铂-吉西他滨为 66.2%（事件或死亡的风险比为 0.53；95% 置信区间 [CI]，0.41 至 0.70；P<0.001）；估计的总生存率分别为 86.9% 和 81.3%（死亡风险比为 0.65；95% CI，0.48 至 0.89；双侧 P = 0.006）。

A pathological complete response occurred in 55.8% and 32.5% of the participants (P<0.001).

55.8% 和 32.5% 的参与者出现了病理完全缓解 (P<0.001)。

The incidenceof grade 3 or higher adverse events of any cause was 75.7% with enfortumab vedotin-pembrolizumab and 67.2% with cisplatin-gemcitabine.

使用恩福妥单抗-维多珠单抗的患者中，任何原因导致的3级或更高级别的不良事件发生率为75.7%，而使用顺铂-吉西他滨的患者为67.2%。

Conclusions

Among participants with muscle-invasive bladder cancer eligible for cisplatin-based chemotherapy, perioperative enfortumab vedotin-pembrolizumab led to significantly better event-free and overall survivaloutcomes and a significantly higher incidenceof pathological complete response than neoadjuvant cisplatin-gemcitabine, but with more adverse events of grade 3 or higher.

在符合顺铂化疗条件的肌肉浸润性膀胱癌患者中，围手术期恩福妥单抗-维多珠单抗导致无事件生存和总生存结果显著优于新辅助顺铂-吉西他滨，病理完全缓解的发生率显著更高，但3级或更高级别的不良事件发生率也更高。

(Funded by Merck Sharp and Dohme and others; KEYNOTE-B15/EV-304 ClinicalTrials.gov number, NCT04700124.).

(该研究由默克夏普和多姆等公司资助；KEYNOTE-B15/EV-304临床试验注册号，NCT04700124。)