Pembrolizumab Monotherapy Shows Promise Among Patients With BCG-Unresponsive, High-Risk NMIBC With Papillary Tumors, Without Carcinoma in Situ

Results From Cohort B of the KEYNOTE-057 Trial

According to results from cohort B of the phase 2 KEYNOTE-057 trial, pembrolizumab monotherapy demonstrated promising activity with manageable toxicity among patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk non-muscle invasive bladder cancer (NMIBC) with papillary tumors and without carcinoma in situ. 

As previously reported in patients with carcinoma in situ and with or without papillary tumors, “pembrolizumab monotherapy led to a complete response rate of 41% at 3 months, and 46% of responders maintained a response lasting at least 12 months,” stated Andrea Necchi, MD, IRCCS San Raffaele Hospital, Milan, Italy, and coauthors.

There were 132 patients enrolled with BCG-unresponsive, high-risk non-muscle invasive bladder cancer, with papillary tumors (Ta or any grade T1) and without carcinoma in situ 12-weeks post transurethral resection of the bladder. Patients receive 200 mg of intravenous pembrolizumab every 3 weeks for a maximum of 35 cycles. The primary end point was 12-month disease-free survival (DFS). A key secondary end point was safety.

At a median follow-up of 45.4 months, patients received a median of 10 cycles of pembrolizumab and 12-month DFS was 43.5%. At that time, 4% of patients remained on treatment protocol. Treatment-related adverse events occurred in 73% of patients. Grade 3/4 treatment-related colitis and diarrhea occurred in 14% of patients. Serious treatment-related colitis occurred in 13% of patients. No treatment-related deaths occurred. 

“Pembrolizumab monotherapy showed antitumour activity and manageable toxicity in patients with BCG-unresponsive high-risk Ta or T1 bladder cancer without carcinoma in situ and could potentially be a suitable treatment option for patients who decline or are ineligible for radical cystectomy,” concluded Dr Necchi et al. “Findings will need to be confirmed in a randomised controlled trial.”

Source: 

Necchi A, Roumiguié M, Kamat AM, et al. Pembrolizumab monotherapy for high-risk non-muscle-invasive bladder cancer without carcinoma in situ and unresponsive to BCG (KEYNOTE-057): A single-arm, multicentre, phase 2 trial. Lancet Oncol. Published online: May 10, 2024. doi:10.1016/S1470-2045(24)00178-5