Pembrolizumab after TMT shows promise in muscle-invasive bladder cancer

Maintenance pembrolizumab (Keytruda) following stereotactic ablative radiotherapy (SABR) boost to bladder tumor and concurrent radio-chemotherapy was found to be both effective and well tolerated in patients with muscle-invasive bladder cancer, according to data presented at the 2024 American Society for Radiation Oncology Annual Meeting in Washington, DC.¹

“The estimated PFS, local control, and OS were 85%, 93%, and 97%, respectively,” Qin reported.

“There has been an increasing trend of utilizing organ-preserving therapies in the management of bladder cancer over the past decades. TMT [tri-modal therapy], including [transurethral resection of bladder tumor], chemotherapy, and radiotherapy, is an established multi-disciplinary approach for bladder preservation with outcomes that are comparable to those of radical cystectomy. However, [previous research] has shown the 5-year local recurrence in the bladder is close to 40%, and 5-year distant metastasis was more than 30%.² Our pilot study showed that the strategy for SABR boost as part of TMT was well tolerated and effective in [patients with] MIBC. So we conducted this study to evaluate the effectiveness of pembrolizumab as maintenance therapy following TMT in [patients with] bladder cancer,” said study author Shang-bin Qin, MD, of Peking University First Hospital, Beijing, China.

The primary end point for the study was PFS. Secondary end points included overall survival (OS), bladder-intact event-free survival, and safety signals.

The study was single arm and single site. Patients received pembrolizumab for 1 year in up to 17 cycles. Patients were eligible if they had cT2-4N0M0 MIBC, declined or were ineligible for radical cystectomy, had an ECOG Performance Status of 0 or 1, had primary bladder cancer with urothelial carcinoma > 50%, and achieved complete response (defined as tumor free on bladder MRI and cystoscopy) after receiving maximal TURBT then SABR.

“Patients received SABR to the tumor or tumor bed in the bladder followed by conventionally fractionated RT to pelvis and total bladder with concomitant weekly low-dose gemcitabine chemotherapy,” wrote the authors. Following TMT, patients who achieved a CR went on to receive maintenance pembrolizumab.

A total of 46 patients were enrolled in the study. Median age was 69 years (range, 34-86 years). In addition, 78% of the patient population was male. In terms of clinical staging, 39 (85%) patients had T2 disease and 7 (15%) patients had T3 disease. Eighteen (39%) patients had complete TURBT vs 28 (61%) patients who had incomplete TURBT. Forty-four (96%) patients received concurrent chemotherapy, and 9 (20%) patients received neoadjuvant chemotherapy.

Median follow-up was 10 months. Ten patients completed 17 cycles of pembrolizumab.

“The estimated PFS, local control, and OS were 85%, 93%, and 97%, respectively,” Qin reported.

Any-grade treatment-related adverse events (TRAEs) were reported in 11 (24%) patients. Grade 3 TRAEs occurred in 3 (7%) patients and consisted of myocarditis, cystitis, and pneumonitis. Seventeen patients discontinued treatment with pembrolizumab.

“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. Correlative analyses from blood and tissue specimens will be presented in the future,” Qin concluded.

REFERENCES

1. Qin SB, Yu W, He ZS, et al. Pembrolizumab monotherapy following tri-modality treatment for selected patients with muscle-invasive bladder cancer. Presented at: 2024 American Society for Radiation Oncology Annual Meeting. September 29-October 2, 2024. Washington, DC. Abstract 220. https://astro2024.eventscribe.net/agenda.asp?startdate=9/30/2024&enddate=9/30/2024&BCFO=M&pfp=Browse%20by%20Day&fa=&fb=&fc=&fd=

2. Giacalone NJ, Shipley WU, Clayman RH, et al. Long-term outcomes after bladder-preserving tri-modality therapy for patients with muscle-invasive bladder cancer: an updated analysis of the Massachusetts General Hospital experience. Eur Urol. 2017;71(6):952-960. doi:10.1016/j.eururo.2016.12.020