患有膀胱癌（BC）的患者如果无法使用顺铂或者患有不可切除的疾病，治疗选项就比较有限。我们之前已经表明，使用durvalumab（durva）和放疗疗法（RT）联合治疗BC病人的PD-L1为靶点是安全的。我们现在报告一项II期研究的结果，评估durva和RT对局部BC毒副作用和疗效的影响。这是一项单臂和多机构II期研究，N=26。纳入的患者有未切除的肿瘤，不能接受手术或者不能使用顺铂的UBC（T2-4 N0-2 M0）。患者在接受7周的RT时，同时接受durva治疗，之后再进行durva辅助治疗1年。(A) 一年进展生存期（PFS）和(B) 接受durva辅助治疗后的疾病控制率（DCR）。关键次要终点：(A)在durvaRT后的完全缓解（CR）（8周），(B)总生存期(OS),(C)PFS和(D)毒副作用。相关研究包括对基线肿瘤和血液（基线、durvaRT后）的生物标志物进行评估。中位随访时间为27个月。可评价的患者：24/26在durvaRT后，22/26在接受durva辅助治疗时进行了DCR评估，所有患者都进行了PFS和OS评估。在接受durva辅助治疗后，DCR为72.7％，CR为54.5％。一年PFS为71.5％，中位PFS为21.8个月。1年OS为83.8％，中位OS为30.8个月。durvaRT后8周的CR为62.5％。N + 患者的中位PFS和OS相似。durvaRT耐受性良好。等级≥3的与治疗相关的不良事件：贫血、高脂酶/淀粉酶、免疫性肾炎、转氨酶增高、呼吸困难(4级COPD/免疫反应)、疲劳、皮疹、腹泻和巩膜炎。没有发现基线肿瘤的PD-L1状态与结果之间的差异。具有CR / PR或SD的患者，其CD4 T细胞数量增加，PD-1 + CD4 T细胞数量减少，在外周血中的分泌细胞包括干扰素γ（IFNγ）产生细胞的CD8T细胞数量增加。Durva与RT并进行补充治疗，对患有N +患者的并发症的局部BC患者具有安全性和有前途的疗效。需要进行更大规模的随机研究，例如S1806和EA8185，以评估在BC中结合免疫疗法和放疗疗法的疗效。NCT02891161。©作者(或其雇主)（2023）。在CC BY-NC许可下重新使用。不得进行商业再利用。由BMJ出版。

Patients with bladder cancer (BC) who are cisplatin ineligible or have unresectable disease have limited treatment options. Previously, we showed targeting programmed death-ligand 1 (PD-L1) with durvalumab (durva) and radiation therapy (RT) combination was safe in BC. We now report results from a phase II study evaluating the toxicity and efficacy of durva and RT in localized BC.This is a single-arm, multi-institutional phase II study; N=26. Enrolled patients had pure or mixed urothelial BC (T2-4 N0-2 M0) with unresectable tumors and were unfit for surgery or cisplatin ineligible. Patients received durva concurrently with RT ×7 weeks, followed by adjuvant durva × 1 year.(A) progression-free survival (PFS) at 1 year and (B) disease control rate (DCR) post adjuvant durva. Key secondary endpoints: (A) complete response (CR) post durvaRT (8 weeks), (B) overall survival (OS), (C) PFS and (D) toxicity. Correlative studies included evaluation of baseline tumor and blood (baseline, post durvaRT) for biomarkers.Median follow-up was 27 months. Evaluable patients: 24/26 post durvaRT, 22/26 for DCR post adjuvant durva, all patients for PFS and OS. Post adjuvant durva, DCR was seen in 72.7%, CR of 54.5%. 1-year PFS was 71.5%, median PFS was 21.8 months. 1-year OS was 83.8%, median OS was 30.8 months. CR at 8 weeks post durvaRT was 62.5%. Node positive (N+) patients had similar median PFS and OS. DurvaRT was well tolerated. Grade ≥3 treatment-related adverse events: anemia, high lipase/amylase, immune-nephritis, transaminitis, dyspnea (grade 4-COPD/immune), fatigue, rash, diarrhea and scleritis. No difference in outcome was observed with PD-L1 status of baseline tumor. Patients with CR/PR or SD had an increase in naïve CD4 T cells, a decrease in PD-1+CD4 T cells at baseline and an increase in cytokine-producing CD8 T cells, including interferon gamma (IFNγ) producing cells, in the peripheral blood.Durva with RT followed by adjuvant durva was safe with promising efficacy in localized BC patients with comorbidities, including N+ patients. Larger randomized studies, like S1806 and EA8185, are needed to evaluate the efficacy of combining immunotherapy and RT in BC.NCT02891161.© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.