Garje Rohan, Ravindra Aditya, Rahim Bilal, Kroll Mathew, Johnson Jeffrey S, Torres Julie, Bonner Jaime, Packiam Vignesh T, Mott Sarah, O'Donnell Michael, Zakharia Yousef
Division of Hematology, Oncology, and Blood & Bone Marrow Transplantation, University of Iowa Health Care, Iowa City, IA; Genitourinary Medical Oncology, Miami Cancer Institute, Baptist Health Medical Group, Miami, FL; Holden Comprehensive Cancer Center, University of Iowa Hospitals and Clinics, Iowa City, IA.
Division of Hematology, Oncology, and Blood & Bone Marrow Transplantation, University of Iowa Health Care, Iowa City, IA.
Urol Oncol. 2025 Sep;43(9):520.e9-520.e18. doi: 10.1016/j.urolonc.2025.04.005. Epub 2025 May 31.
This study investigates the role of taxanes and immunotherapy for inoperable advanced or metastatic urothelial carcinoma in patients unable to tolerate or refractory to platinum-based regimens. We aimed to determine the safety and estimate the efficacy of a combination of avelumab and docetaxel in treating advanced or metastatic urothelial carcinoma.
This phase 1b, single-arm, open-label clinical trial involved adults with advanced or metastatic urothelial carcinoma, progressing during or after platinum-containing chemotherapy, within 12 months of neoadjuvant or adjuvant platinum-containing chemotherapy, or ineligible for platinum regimens. Primary objectives were determining the maximum tolerated dose (MTD) of docetaxel with avelumab and estimating efficacy via the objective response rate (ORR). In Phase I, docetaxel (45, 60, 75 mg/m²) was combined with 10 mg/kg avelumab every 3 weeks for 6 cycles, followed by avelumab biweekly as maintenance. The expansion cohort received treatment at the MTD of 75 mg/m² docetaxel with 10 mg/kg of avelumab.
Twenty-one patients with advanced or metastatic urothelial carcinoma were studied: 8 cisplatin-refractory and 13 cisplatin-ineligible. The 75 mg/m² dose of docetaxel with 10 mg/kg avelumab was safe, with 1 dose-limiting toxicity (neutropenic fever). The ORR was 52.4% (95% CI: 29.8%-74.3%). Median progression-free survival and overall survival were 14.6 months (95% CI: 2.8-15.8) and 16.6 months (95% CI: 13.2-not reached), respectively.
The combination of avelumab and docetaxel shows favorable safety and efficacy in treating advanced or metastatic bladder cancer.
Funded by Pfizer Pharmaceuticals; AVETAX; https://classic.
gov/ct2/show/NCT03575013, NCT03575013.
本研究探讨紫杉烷类药物和免疫疗法在无法耐受铂类方案或对铂类方案难治的不可切除晚期或转移性尿路上皮癌患者中的作用。我们旨在确定阿维鲁单抗和多西他赛联合治疗晚期或转移性尿路上皮癌的安全性并评估其疗效。
这项1b期单臂开放标签临床试验纳入了患有晚期或转移性尿路上皮癌的成年人，这些患者在含铂化疗期间或之后进展、在新辅助或辅助含铂化疗的12个月内进展或不符合铂类方案标准。主要目标是确定多西他赛与阿维鲁单抗联合使用的最大耐受剂量（MTD），并通过客观缓解率（ORR）评估疗效。在I期，多西他赛（45、60、75mg/m²）每3周与10mg/kg阿维鲁单抗联合使用，共6个周期，随后每两周使用阿维鲁单抗进行维持治疗。扩展队列接受75mg/m²多西他赛与10mg/kg阿维鲁单抗的MTD治疗。
对21例晚期或转移性尿路上皮癌患者进行了研究：8例对顺铂难治，13例不符合顺铂治疗标准。75mg/m²多西他赛与10mg/kg阿维鲁单抗联合使用是安全的，有1例剂量限制性毒性（中性粒细胞减少性发热）。ORR为52.4%（95%CI：29.8%-74.3%）。中位无进展生存期和总生存期分别为14.6个月（95%CI：2.8-15.8）和16.6个月（95%CI：13.2-未达到）。
阿维鲁单抗和多西他赛联合治疗晚期或转移性膀胱癌显示出良好的安全性和疗效。
由辉瑞制药公司资助；AVETAX；https://classic.
gov/ct2/show/NCT03575013，NCT03575013。
