Dr Li on the Rationale for a Post Hoc Analysis of KEYNOTE-057 in BCG-Unresponsive NMIBC

Roger Li, MD, genitourinary oncologist, Moffitt Cancer Center, discusses results from the phase 2 KEYNOTE-057 trial (NCT02625961) that have been previously reported, detailing how the trial led way to a post hoc analysis of patients with Bacillus Calmette-Guérin (BCG)–unresponsive, high-risk non–muscle-invasive bladder cancer (NMIBC) who did not respond to treatment with pembrolizumab (Keytruda) on the study.

KEYNOTE-057 was the first study that evaluated pembrolizumab in patients with BCG-unresponsive NMIBC, Li begins. The trial was structured into 2 cohorts; cohort A included patients with carcinoma in situ (CIS)–containing tumors, and cohort B consisted of patients with papillary-only tumors. The study assessed the efficacy of pembrolizumab in these disease settings, he explains.

For cohort A, the primary end point was the complete response (CR) rate at 3 months, which was found to be 41%, Li reports. This result demonstrated a significant level of effectiveness for pembrolizumab in patients with CIS-containing tumors, according to Li. For cohort B, the primary end point was the 12-month disease-free survival rate, which was reported in 2023 as 43.5%, he explains. These findings were crucial in securing FDA approval for pembrolizumab’s use in patients with BCG-unresponsive NMIBC, making it a new therapeutic option for patients with limited treatment alternatives, Li notes.

The rationale for conducting a post hoc analysis of KEYNOTE-057 stemmed from the observation that, despite pembrolizumab’s FDA approval, many patients still experience disease recurrence after treatment, he continues. These patients are often elderly and frail, making radical cystectomy, the standard treatment for nonresponse, a less viable option due to its associated risks and impact on quality of life, Li emphasizes. The purpose of the post hoc analysis was to determine whether patients who continued on a bladder-sparing therapeutic strategy, rather than undergoing immediate radical cystectomy, faced poorer outcomes after developing a nonresponse to pembrolizumab, Li states. This analysis provided insights into the potential benefits of less aggressive treatment approaches for this vulnerable patient population, he concludes.