Dr Singer on Systemic Pembrolizumab Monotherapy in BCG-unresponsive High-Risk NMIBC

Eric A. Singer, MD, professor of Urology and Bioethics, director, Division of Urologic Oncology, The Ohio State University Wexner Medical Center, The Ohio State University Comprehensive Cancer Center–James, discusses the use of systemic pembrolizumab (Keytruda) monotherapy in patients with Bacillus Calmette-Guérin (BCG)–unresponsive, high-risk non–muscle invasive bladder cancer (NMIBC).

The phase 2 KEYNOTE-057 trial (NCT02625961) was designed to evaluate the use of single-agent pembrolizumab in 2 cohorts of patients with high-risk BCG-unresponsive NMIBC, Singer says. Cohort A consisted of patients with carcinoma in situ (CIS) with or without papillary tumors, and cohort B included those with non-CIS papillary tumors. Patients in both cohorts were previously treated with 2 induction courses of BCG and were either ineligible for, or declined to undergo, radical cystectomy, Singer says. Pembrolizumab was delivered intravenously to provide systemic effects, Singer adds. The study's primary end point was a disease-free survival (DFS) rate greater than 20%.

Previously reported results from cohort A showed that the clinical CR rate with pembrolizumab in cohort A was 41% at 3 months, with a median duration of 16.2 months. In January 2020, the FDA approved pembrolizumab for use in this population according to these findings.

Data from cohort B were presented at the 2023 AUA Annual Meeting. In this cohort of 132 patients, pembrolizumab monotherapy produced a 12-month DFS rate of 43.5% at a median follow-up of 45.4 months, Singer reports. The median DFS was 7.7 months. Although 27% of patients subsequently underwent radical cystectomy, many other patients were able to avoid or considerably delay this procedure, Singer notes.

These data suggest that systemic pembrolizumab monotherapy is another viable option for patients with recurrent high-grade NMIBC who have progressed on BCG, Singer concludes.