食品药品监管局批准度伐利尤单抗联合疗法用于肌层浸润性膀胱癌
美国食品药品监管局（FDA）11月13日批准度伐利尤单抗（durvalumab，商品名 Imfinzi，阿斯利康）与 enfortumab vedotin-ejfv 联合用药，用于不适合含顺铂化疗或拒绝该化疗的成年肌层浸润性膀胱癌患者：手术前作新辅助治疗，根治性膀胱切除术后以度伐利尤单抗单药作辅助治疗。
疗效在 VOLGA 随机开放标签试验中评估，该试验共入组695名可接受根治性膀胱切除、且不适合或拒绝含顺铂化疗的患者，按1比1比1随机分组。主要疗效指标是经盲法独立中心评估的无事件生存期，总生存期是另一项疗效指标。
结果显示，联合治疗组的无事件生存期显著优于单纯手术组：联合组中位无事件生存期尚未达到，单纯手术组为12.1个月，风险比0.51，双侧p值小于0.0001。总生存方面两组中位值都尚未达到，风险比0.58，双侧p值0.0027。
推荐剂量按体重区分：体重30公斤及以上患者，手术前度伐利尤单抗每3周1500毫克、联合 enfortumab vedotin-ejfv 每公斤1.25毫克（每周期第1天和第8天），共3个周期；术后度伐利尤单抗单药每4周1500毫克，最多9个周期。体重低于30公斤者度伐利尤单抗按每公斤20毫克计。治疗持续到疾病进展导致无法手术、复发、出现不可接受的毒性，或术后满9个周期为止。
食品药品监管局说，度伐利尤单抗的说明书警告包括免疫介导不良反应、输液相关反应、异基因造血干细胞移植并发症和胚胎胎儿毒性；联合用药最常见的不良反应包括肝酶升高、血红蛋白下降、皮疹、肌酐升高和瘙痒等。此次审评通过该局肿瘤卓越中心的 Project Orbis 与澳大利亚、巴西、加拿大、以色列、新加坡和英国的监管机构协作进行，获优先审评，批准时间比目标日期提前了六周。
（来源：美国食品药品监管局）
FDA Approves Durvalumab Combination for Muscle Invasive Bladder Cancer
The U.S. Food and Drug Administration (FDA) on November 13 approved durvalumab (Imfinzi, AstraZeneca) in combination with enfortumab vedotin-ejfv as neoadjuvant treatment, followed by single-agent durvalumab as adjuvant treatment after radical cystectomy, for adult patients with muscle invasive bladder cancer who are ineligible for or have refused cisplatin-based chemotherapy.
Efficacy was evaluated in VOLGA, a randomized, open-label trial that enrolled 695 patients with muscle invasive bladder cancer who were candidates for radical cystectomy and were ineligible for or refused cisplatin-based chemotherapy, randomized 1:1:1. The major efficacy outcome was event-free survival by blinded independent central review, and overall survival was an additional outcome.
The trial showed statistically significant improvements in both measures for the combination compared with surgery alone. Median event-free survival was not reached in the combination arm and was 12.1 months in the surgery-alone arm, with a hazard ratio of 0.51 and a two-sided p-value below 0.0001. Median overall survival was not reached in either arm, with a hazard ratio of 0.58 and a two-sided p-value of 0.0027.
For patients weighing at least 30 kg, the recommended durvalumab dose is 1,500 mg every 3 weeks with enfortumab vedotin-ejfv 1.25 mg/kg on Days 1 and 8 of each cycle for 3 cycles before surgery, followed by durvalumab 1,500 mg every 4 weeks for up to 9 cycles after surgery. For patients under 30 kg, the durvalumab dose is 20 mg/kg on the same schedule. Treatment continues until disease progression that precludes definitive surgery, recurrence, unacceptable toxicity, or a maximum of 9 cycles after surgery.
The FDA said durvalumab prescribing information includes warnings for immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic hematopoietic stem cell transplantation, and embryo-fetal toxicities, and that the most common adverse reactions included increased AST and ALT, decreased hemoglobin, rash, increased creatinine, and pruritus. The review was conducted under Project Orbis of the FDA Oncology Center of Excellence with regulators in Australia, Brazil, Canada, Israel, Singapore, and the United Kingdom, was granted priority review, and was approved six weeks ahead of the FDA goal date.
(Source: U.S. Food and Drug Administration)
来源：美国食品药品监管局
发布：GSM·美国（发布链接）
图片来源：图：美国食品药品监管局（FDA）总部大楼（固定图库联邦核心包）。 / Photo: Headquarters of the U.S. Food and Drug Administration (fixed federal-core asset-pack image).
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