Perioperative Enfortumab Vedotin and Pembrolizumab in Bladder Cancer.

Perioperative therapy may improve outcomes in this population.

围手术期治疗可能改善这一人群的治疗结果。

Methods

In this phase 3, open-label trial, participants with muscle-invasive bladder cancer who were ineligible for or declined cisplatin-based chemotherapy were randomly assigned to perioperative (neoadjuvant and adjuvant) enfortumab vedotin, an antibody-drug conjugate directed at nectin-4, plus pembrolizumab and surgery (9 total cycles of enfortumab vedotin [1.25 mg per kilogram of body weight on days 1 and 8] plus 17 total cycles of pembrolizumab [200 mg on day 1 every 3 weeks], with surgery after 3 cycles) or surgery alone (control).

在这项III期、开放标签的试验中，不符合或拒绝顺铂为基础化疗的肌层浸润性膀胱癌患者被随机分配到围手术期（新辅助和辅助）接受靶向nectin-4的抗体药物偶联物enfortumab vedotin，联合pembrolizumab和手术治疗（总共9个周期的enfortumab vedotin[第1天和第8天每公斤体重1.25毫克]加上总共17个周期的pembrolizumab[每3周第1天200毫克]，手术在3个周期后进行），或单独手术治疗（对照组）。

The primary end point was event-free survival. Key secondary end points were overall survivaland pathological complete response (absence of viable tumor after surgical resection).

主要终点是无事件生存期。关键的次要终点是总生存期和病理完全缓解（手术切除后无活肿瘤）。

Other secondary end points included safety.

其他次要终点包括安全性。

Results

A total of 344 participants underwent randomization (170 in the enfortumab vedotin-pembrolizumab group and 174 in the control group).

共有344名参与者进行了随机分组（170名在恩福他莫单抗-帕博利珠单抗组，174名在对照组）。

At data cutoff, median follow-up was 25.6 months (range, 11.8 to 53.7).

数据截止时，中位随访时间为25.6个月（范围，11.8至53.7个月）。

Surgery was performed in 87.6% of participants in the enfortumab vedotin-pembrolizumab group and in 89.7% in the control group.

在enfortumab vedotin-pembrolizumab组中，87.6%的参与者接受了手术，在对照组中，89.7%的参与者接受了手术。

At 2 years, estimated event-free survival was 74.7% in the enfortumab vedotin-pembrolizumab group and 39.4% in the control group (hazard ratiofor an event or death, 0.40; 95% confidence interval[CI], 0.28 to 0.57; two-sided P<0.001); estimated overall survivalwas 79.7% and 63.1% (hazard ratiofor death, 0.50; 95% CI, 0.33 to 0.74; two-sided P<0.001).

在2年时，enfortumab vedotin-pembrolizumab组的无事件生存率估计为74.7%，对照组为39.4%（事件或死亡的风险比为0.40；95%置信区间[CI]，0.28至0.57；双侧P<0.001）；估计的总生存率分别为79.7%和63.1%（死亡风险比为0.50；95% CI，0.33至0.74；双侧P<0.001）。

A pathological complete response had occurred in 57.1% and 8.6% of the participants (estimated difference, 48.3 percentage points; 95% CI, 39.5 to 56.5; two-sided P<0.001).

57.1%的参与者发生了病理完全缓解，而对照组为8.6%（估计差异为48.3个百分点；95% CI，39.5至56.5；双侧P<0.001）。

Adverse events occurred in all participants in the enfortumab vedotin-pembrolizumab group (grade ≥3, 71.3%; grade ≥3 drug-related, 45.5%) and in 64.8% in the control group (grade ≥3, 45.9%).

所有接受恩沃利单抗-帕博利珠单抗治疗组的参与者均出现了不良事件（3级及以上不良事件发生率为71.3%；3级及以上药物相关不良事件发生率为45.5%），而对照组为64.8%（3级及以上不良事件发生率为45.9%）。

Conclusions

Perioperative enfortumab vedotin plus pembrolizumab and surgery led to significantly better event-free and overall survivaloutcomes and a greater percentage of participants with pathological complete response than surgery alone in a predominantly cisplatin-ineligible population with muscle-invasive bladder cancer.

在主要为顺铂不耐受的肌层浸润性膀胱癌患者中，围手术期恩沃利单抗联合帕博利珠单抗和手术治疗相较于单独手术，显著改善了无事件生存和总生存结果，并且有更多的参与者达到了病理完全缓解。

Safety was also assessed.

安全性评估也被进行。

(Funded by Merck Sharp and Dohme, a subsidiary of Merck [Rahway, NJ]; KEYNOTE-905 ClinicalTrials.gov number, NCT03924895.).

该研究由默克夏普和多姆公司资助，该公司是默克公司（位于新泽西州拉霍伊）的一个子公司；KEYNOTE-905临床试验注册号为NCT03924895。