Pembrolizumab Monotherapy Following Tri-modality Treatment for Selected Patients With Muscle-invasive Bladder Cancer

This is a Phase II, single-arm, study of pembrolizumab as maintenance therapy in muscle-invasive bladder cancer (MIBC) participants who have received maximum TURBT and tri-modality treatment (TMT) and achieved CR. All participants will receive pembrolizumab monotherapy per 21 days no longer than 17 cycles until disease progression or death.

Radical cystectomy (RC) has long been the standard of care for the treatment of muscle-invasive bladder cancer (MIBC). Modern RC series have demonstrated 5-yr overall survival (OS) rates of 56-66%. There has been an increasing trend of utilizing organ-preserving therapies in the management of bladder cancer over the past several decades. A multidisciplinary approach has led to the development of bladder-sparing approaches using maximal transurethral resection (TURBT) followed by radiotherapy with concomitant radio-sensitizing chemotherapy for MIBC. Multiple tri-modality treatment (TMT) series have suggested that TMT can yield favorable results in well-selected patients. The 5-yr OS is 48-75%, and 75-80% of the survivors have preserved their native bladder. Even if local recurrence occurred after concurrent radio-chemotherapy, salvage cystectomy can also bring 50-57.6% of 5-year disease-specific survival (DSS) without more complications associated with surgery. So, NCCN guidelines have regarded this TMT strategy as a preferred choice for patients with MIBC since 2019. However, distant metastasis after TMT was still the main concern. Giacalone NJ, et al. reported that the 5-yr distant metastasis rate was 32% in MIBC patients who received an organ-preserving strategy. Up to now, there was no consensus on adjuvant therapy after concurrent radio-chemotherapy. Some retrospective studies demonstrated that adjuvant chemotherapy had no survival benefit, and only approximately 50% of patients completed the planned adjuvant chemotherapy due to intolerable toxicities. These years, studies on PD-(L)1 inhibitors for urothelial carcinoma showed the efficacy and safety. FDA has approved indications of pembrolizumab used as 1L (selected patients) and 2L treatment for metastatic urothelial carcinoma. Checkmate-274 has reported that adjuvant immunotherapy improved disease-free survival (DFS) in MIBC patients after RC. Javelin Bladder 100 prolonged OS of mUC patients by Avelumab as maintenance therapy who achieved CR, PR or PD after 1L chemotherapy. These results support our hypothesis that, for those MIBC patients who have received bladder-preserving TMT and achieved CR, pembrolizumab monotherapy as maintenance therapy is superior to observation.