Pembrolizumab (pembro) with chemoradiotherapy (CRT) as treatment for muscle-invasive bladder cancer (MIBC): Long-term follow up of secondary endpoints of efficacy including overall survival of the PCR-MIB phase II clinical trial (ANZUP 1502).

• DOI: 10.1200/jco.2025.43.16_suppl.4577
• Publication Date: 2025-05-28T13:29:58Z
• Authors: Andrew James Weic...; Farshad Foroudi; Nathan Lawrentschuk; Jing Xie; Yi-An Ko; Mark Sidhom; Abhijit Pal; Peter S. Grimison; Alison Yan Zhang; Siobhan Ng; Colin Tang; Elizabeth Jane Hovey; Colin Chen; George Hruby; Alexander David G...; Samantha Richelle...; Ciara Conduit; Ben Tran; Ian D. Davis; Dickon Hayne
• Keywords: Chemoradiotherapy; Clinical endpoint; Urothelial cancer

4577 Background: We hypothesised pembro could be added without undue toxicity to CRT and would improve efficacy in patients (pts) with MIBC. Methods: This multicentre phase 2 trial included people non-metastatic cT2-T4aN0M0 MIBC (>50% urothelial histology) who declined cystectomy or for whom was unsuitable, no contraindications pembro, ECOG performance status 0 1, eGFR ≥40 mL/min. Neoadjuvant chemotherapy not permitted. Pts had maximal TURBT, then whole bladder radiation therapy (RT) (64Gy 32 daily fractions, mostly IMRT) over 6.5 weeks weekly cisplatin (35 mg/m IV, 6 doses) 200mg IV q3wk x 7 doses, both starting RTx. Surveillance cystoscopy, urine cytology, CT chest-abdomen-pelvis were performed 12 & 24 after CRT. The primary endpoint feasibility, determined by a prespecified satisfactory low rate of grade 3-4 non-urinary toxicity, completion planned within defined parameters (RT < weeks, >1 dose omission). Secondary endpoints include complete cystoscopic response metastatic disease at distant metastases free survival (DMFS), overall (OS), loco-regional progression (LRPFS). Longer term follow up (median 54 months) is presented here from the November 2024 analysis. Results: From 2016 – 2021, 28 pts (93% male, median age 72, 96% pure carcinoma, 29% carcinoma situ, 90% pT2) enrolled sites. At 48 months, DFMS 68% (95% CI 46-82%), OS 64 % 42-79%), reached 25.6m NE). Local-regional failure months 84% 63 94). Complete (CR) post 88% 70-98%, 23 CR, 3 PD, regimen deemed feasible as previously presented: Gr >3 any adverse events (AEs) during treatment completing (2 delay RT >7 wks), reductions due G2 AEs. 1 pt G3 colitis, polymyalgia, nephritis. There additional immune related reported longer follow-up. Conclusions: shows promising OS, DMFS LRPFS combination new events. Larger randomised trials test this approach are ongoing. Clinical information: NCT02662062 .