期刊
CLINICAL CANCER RESEARCH
卷 29, 期 19, 页码 3875-3881出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-23-0354
关键词
-
类别
Durvalumab monotherapy showed minimal efficacy in treating BCG-unresponsive carcinoma in situ (CIS) of the bladder, with a 6-month complete response rate of 12%. Complement activation may be a potential mechanism behind treatment resistance.
Purpose: Immune checkpoint blockade holds promise for treating bacillus Calmette-Guerin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC). In this phase II study, we investigated the safety and efficacy of durvalumab, a human IgG1 monoclonal antibody, against BCG-unresponsive carcinoma in situ (CIS).Patients and Methods: Patients with BCG-unresponsive CIS-containing NMIBC received durvalumab IV at 1,500 mg every 4 weeks for up to 12 months. The primary endpoint was complete response (CR) rate at month 6, defined by negative cystoscopy, urine cytology, and absence of high-grade recurrence on bladder mapping biopsy. The null hypothesis specified a CR rate of 18% and alternative hypothesis of 40%. According to the Simon two-stage design, if <= 3/13 patients achieved CR during stage 1, the trial is stopped due to futility.Results: Between March 8, 2017, and January 24, 2020, 17 patients were accrued whereas 4 withdrew from study treatment after bladder biopsy at month 3 was positive for CIS. Two of 17 (12%) achieved a CR at month 6, with duration of response of 10 and 18 months, respectively. A single grade 3 lipase elevation was attributed to durvalumab, and immune-related adverse events were observed in 7/17 (41%) patients. Only 1/17 patients had high programmed death-ligand 1 expression pretreatment. On RNA sequencing, complement activation genes were elevated posttreatment, along with enrichment of tumor-associated macrophage signature.Conclusions: Durvalumab monotherapy conferred minimal efficacy in treating BCG-unresponsive CIS of the bladder, with 6-month CR of 12%. Complement activation is a potential mechanism behind treatment resistance.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据