S. B. Qin1, W. Yu2, Z. S. He2, X. S. Gao1, H. Hao2, H. Z. Li1, and Y. Bai1; 1Department of Radiation Oncology, Peking University First Hospital, Beijing, China, 2Department of Urology, Peking Universtiy First Hospital, Beijing, China
Purpose/Objective(s):This is a Phase 2, single arm, single-site study of Pembrolizumab as maintenance therapy in muscle-invasive bladder cancer (MIBC) participants who has received maximum Transurethral resection of bladder tumor (TURBT) and tri-modality treatment (TMT) and achieved complete response (CR). Materials/
Methods: This trial includes Patients with cT2-4N0M0 MIBC who declined or were ineligible for cystectomy (RC), ECOG PS 0/1, urothelial carcinoma > 50%, and achieved CR after receiving maximal TURBT then Stereotactic ablative radiotherapy (SABR) boost to bladder tumor or tumor bed and concurrent radio-chemotherapy. Patients received SABR to the tumor or tumor bed in the bladder followed by conventionally fractionated RT (CFRT) to pelvis and total bladder with concomitant weekly low-dose Gemcitabine chemotherapy. During SABR, intravesical installation of isovolumetric saline through urinary catheter ensured adequate bladder filling. After TMT, patients who achieved CR will receive Pembrolizumab as maintenance therapy. Pembrolizumab (200 mg q3w) monotherapy will begin on Day 1 of each 3-week cycle and will continue for up to 17 cycles. The primary endpoint was progression-free survival (PFS). Results: From January 11, 2022 to March 7, 2024, forty-six patients with MIBC were enrolled. The median age of included patients was 69 years (IQR 34-86) and clinical stage ranged from cT2 (n=39) to cT3 (n=7). TURBT was visibly complete in eighteen cases. Nine patients received neoadjuvant chemotherapy before chemoradiotherapy. Forty-four patients received concurrent weekly Gemcitabine chemotherapy during RT. After a median follow-up time of 10 months, ten patients completed Pembrolizumab for 17 cycles. seventeen patients stopped immunotherapy, one due to death caused by pulmonary infection, one severe hematuria, two local recurrence, two distant metastasis, three concomitant diseases (high blood pressure, atrial fibrillation and coronary heart disease), and eight immune-related adverse effects (AEs).11/46 (24%) patients reported immune-related AEs, of which 3 (7%) patients experienced severe toxicity (G3) including myocarditis, pneumonitis, and cystitis. The estimated 1-year PFS, overall survival and local control rate was 85%, 97% and 93%. Two patients experienced intravesical recurrence, two patients reported bone and lung metastasis respectively. One patient received salvage cystectomy due to severe hematuria. One patient died from pulmonary infection related to COVID-19, the others are alive with no evidence of cancer and with intact well-functioning urinary bladder at median follow-up of 10 months. Conclusion: Pembrolizumab maintenance therapy after SABR boost to bladder tumor and concurrent radio-chemotherapy was well-tolerated with promising efficacy in the early analysis. Immune related toxicity was consistent with prior monotherapy trials. Selected correlative analyses from serially collected blood and tissue specimens will be presented.
