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).

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