Dr Li on Patient Outcomes From the KEYNOTE-057 Trial in BCG-Unresponsive NMIBC

Roger Li, MD, genitourinary oncologist, Moffitt Cancer Center, discusses results 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) in the phase 2 KEYNOTE-057 trial (NCT02625961).

Primary results from KEYNOTE-057 demonstrated that pembrolizumab can serve as a bladder-sparing option for patients with high-risk NMIBC who are BCG-unresponsive and are unable or unwilling to undergo radical cystectomy. However, the outcomes of patients who do not respond to bladder-sparing therapies, including pembrolizumab, are of concern. Accordingly, Li and colleagues conducted a post hoc analysis of the KEYNOTE-057 trial to assess the clinical outcomes of patients who experienced persistent or recurrent high-risk NMIBC despite pembrolizumab therapy and subsequently received either radical cystectomy or other bladder-sparing therapies.

The analysis focused on progression-free survival (PFS), metastasis-free survival (MFS), and overall survival (OS), Li says. Patients with BCG-unresponsive carcinoma in situ (CIS) and/or papillary-only tumors who had nonresponse during treatment with pembrolizumab were divided into 3 different groups based on the timing of their radical cystectomy after non-response to pembrolizumab, using the 4-month mark as a categorization point, he explains. These groups included patients who underwent immediate radical cystectomy within the first 4 months, those who had late radical cystectomy after 4 months, and those who did not undergo radical cystectomy at all, opting instead for other bladder-sparing therapies, Li details.

Key findings from this analysis were presented at the 2024 ASCO Annual Meeting, and revealed no significant differences in PFS, MFS, or OS among these 3 groups, Li reports. Additionally, a comparison of patients who underwent radical cystectomy within the first 4 months vs those who had it after 4 months showed no difference in the distribution of pathological staging. These findings suggest that the timing of radical cystectomy following non-response to pembrolizumab does not impact key survival outcomes and that patients may have flexible options for managing persistent or recurrent high-risk NMIBC after pembrolizumab therapy, he concludes.