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

Roger Li, MD, genitourinary oncologist, Moffitt Cancer Center, discusses the clinical implications of findings from 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 phase 2 KEYNOTE-057 trial (NCT02625961).

Previously, investigators shared data from the KEYNOTE-057 trial, which demonstrated superiority with pembrolizumab as a bladder-sparing treatment option for patients with high-risk NMIBC unresponsive to BCG. At the 2024 ASCO Annual Meeting, investigators shared insights from a post hoc analysis that was conducted to evaluate the clinical outcomes of patients from KEYNOTE-057 who either proceeded with radical cystectomy or received other bladder-sparing treatments following progression on pembrolizumab. The post hoc analysis showed that oncologic outcomes were comparable between patients treated with bladder-sparing therapies vs radical cystectomy after pembrolizumab nonresponse, indicating that patients were not adversely affected by bladder-sparing therapy following pembrolizumab.

The clinical implications of these findings are significant, particularly in the context of treating patients with BCG-unresponsive bladder cancer, Li begins. The absence of notable differences in clinical outcomes among the 3 groups studied indicates that it is safe to continue treating patients even after they have developed BCG-unresponsive disease during their initial salvage therapy, he explains. This is a crucial insight because it underscores the possibility of prolonging bladder preservation strategies rather than immediately resorting to radical cystectomy, he states.

In recent years, several new agents have been approved by the FDA for use in this specific setting, offering more treatment options for patients, Li continues. The findings from this post hoc analysis support the notion that these treatments can be safely administered following progression on pembrolizumab without compromising patient outcomes, he adds. For oncologists, this evidence reinforces the viability of bladder-sparing approaches, providing reassurance that delaying more invasive procedures like cystectomy can be a safe and effective strategy for managing BCG-unresponsive bladder cancer, Li concludes.