Olivia Newton-John Cancer and Wellness Centre, Austin Hospital, Melbourne, Australia.
Olivia Newton-John Cancer and Wellness Centre, Austin Hospital, Melbourne, Australia.
Eur Urol Oncol. 2024 Jun;7(3):469-477. doi: 10.1016/j.euo.2023.09.011. Epub 2023 Oct 7.
Radiation may improve the efficacy of immune checkpoint inhibition. This study investigates the combination of pembrolizumab and chemoradiation (CRT) for muscle-invasive bladder cancer (MIBC).
To assess the feasibility and safety of pembrolizumab combined with CRT for MIBC.
DESIGN, SETTING, AND PARTICIPANTS: A single-arm phase 2 trial was performed with 28 participants having cT2-T4aN0M0 MIBC (Eastern Cooperative Oncology Group performance status 0-1; estimated glomerular filtration rate ≥40 ml/min; no contraindications to pembrolizumab) suitable for CRT.
Whole bladder radiation therapy (RT; 64 Gy in 32 daily fractions, over 6.5 wk, combined with cisplatin (35 mg/m intravenously [IV] weekly, six doses) and pembrolizumab (200 mg IV q3 weeks, seven doses), both starting with RT. Surveillance cystoscopy/biopsy and computerised tomography scans performed 12 and 24 wk after CRT.
The primary endpoint was feasibility, determined by a prespecified satisfactory low rate of grade 3 or worse nonurinary toxicity or completion of planned CRT according to defined parameters. Secondary endpoints were complete cystoscopic response, locoregional progression-free survival (LRPFS), distant metastasis-free survival (DMFS), and overall survival (OS).
Twenty-eight patients were enrolled with a 31-mo median follow-up. Six had Grade >3 nonurinary adverse events during/within 12 wk after treatment; three had more than one cisplatin dose reduction. The 24-wk post-CRT complete response (CR) rate was 88%. Eight patients developed metastatic disease, and three had nonmetastatic progression. The DMFS at 2 yr is 78% (95% confidence interval [CI] 54-90%), with LRPFS at 2 yr of 87% (95% CI 64-96%) and median OS of 39 mo (95% CI 17.1-not evaluable). Limitations are the single-arm design and sample size.
Combining pembrolizumab with CRT for MIBC was feasible, with manageable toxicity and promising CR rates.
Immunotherapy treats nonmetastatic/metastatic bladder cancer effectively. We combined pembrolizumab with chemotherapy and radiation to assess its safety and impact on treatment delivery. The combination was feasible with encouraging early activity. Further larger trials are warranted.
放疗可能会提高免疫检查点抑制剂的疗效。本研究探讨了帕博利珠单抗联合放化疗（CRT）治疗肌层浸润性膀胱癌（MIBC）。
评估帕博利珠单抗联合 CRT 治疗 MIBC 的可行性和安全性。
设计、地点和参与者：这是一项单臂 2 期临床试验，纳入了 28 例适合 CRT 的 cT2-T4aN0M0 MIBC 患者（东部肿瘤协作组体力状况 0-1 分；估算肾小球滤过率≥40ml/min；无帕博利珠单抗使用禁忌）。
全膀胱放疗（RT；64Gy/32 次，6.5 周，联合顺铂[35mg/m 静脉内（IV）每周一次，共 6 剂]和帕博利珠单抗[200mg IV 每 3 周一次，共 7 剂]，均从 RT 开始）。在 CRT 后 12 周和 24 周进行膀胱镜检查/活检和计算机断层扫描。
主要终点是可行性，通过预定的较低的 3 级或更高级别的非尿毒性或按规定参数完成计划 CRT 的发生率来确定。次要终点是完全膀胱镜反应、局部区域无进展生存期（LRPFS）、远处无转移生存期（DMFS）和总生存期（OS）。
28 例患者入组，中位随访时间为 31 个月。6 例患者在治疗期间/治疗后 12 周内发生 3 级或更高级别的非尿毒性不良事件；3 例患者顺铂剂量减少超过 1 次。24 周 CRT 后完全缓解（CR）率为 88%。8 例患者发生远处转移，3 例患者发生非远处转移进展。2 年 DMFS 为 78%（95%置信区间[CI]：54-90%），2 年 LRPFS 为 87%（95% CI：64-96%），中位 OS 为 39 个月（95% CI：17.1-不可评估）。局限性在于单臂设计和样本量。
帕博利珠单抗联合 CRT 治疗 MIBC 是可行的，具有可管理的毒性和有希望的 CR 率。
免疫疗法可有效治疗非转移性/转移性膀胱癌。我们将帕博利珠单抗与化疗和放疗联合使用，以评估其安全性和对治疗效果的影响。该联合治疗方案具有可行性，且早期疗效令人鼓舞。需要进一步开展更大规模的试验。
