Dr. Necchi on Key Results From Cohort B of the KEYNOTE-057 Trial in MIBC

Andrea Necchi, MD, director of Genitourinary Medical Oncology, IRCCS San Raffaele Hospital and Scientific Institute, associate professor, Vita-Salute San Raffaele University, Milan, Italy, discusses updated analysis of cohort B in the phase 2 KEYNOTE-057 trial (NCT02625961) in non-muscle invasive bladder cancer (nMIBC).

The multicohort study evaluated the activity of pembrolizumab (Keytruda) monotherapy in patients with Bacillus Calmette-Guerin (BCG)-unresponsive nMIBC who declined or were ineligible for cystectomy, Necchi begins.

Three-year follow-up data from cohort A of the study were previously published and demonstrated that single-agent pembrolizumab produced clinically meaningful responses and was well tolerated in patients with histologically confirmed BCG-unresponsive carcinoma in situ (CIS) of the bladder, with or without papillary tumors. These findings led to the FDA approval of pembrolizumab for this population and established the regimen as a standard of care.

Subsequent analysis was conducted in a cohort of patients with high-risk, BCG-unresponsive, nMIBC without a CIS component, Necchi continues. Notably, patients in cohort B were ineligible or elected not to undergo cystectomy, he says. The study’s primary end point was 12-month disease-free survival (DFS).

Results showed that pembrolizumab monotherapy elicited a DFS rate of 43.5% in patients with high-risk disease, Necchi states. Quality of life (QOL) scores were also reported and indicated that QOL was improved or maintained over time in patients who continued treatment and did not experience disease recurrence with pembrolizumab.

Secondary end points such as overall survival (OS) and progression-free survival (PFS) were also encouraging, Necchi continues. The 1-year PFS rate was 88.2%, and the 1-year OS rate was 96.2%. Importantly, median OS was not yet reached at the 45 months of median follow-up.

No new safety signals were observed with the regimen, and its adverse effect (AE) profile is consistent with previously observed data from both cohort A of KEYNOTE-057 and several other disease settings, Necchi notes.

These findings indicate that pembrolizumab monotherapy may be a viable treatment alternative for this patient population with nMIBC, Necchi explains. Continued development of the regimen may require a comparison with a standard of care arm, according to FDA regulations, he concludes.

Editor’s Note: Dr. Necchi reports serving as a consultant or in an advisory role for AstraZeneca, Basilea Pharmaceutical, Bayer, Bristol Myers Squibb, Catalym, Clovis Oncology, GlaxoSmithKline, Incyte, Janssen, Merck Sharp & Dohme, Rainier Therapeutics, Roche, Seattle Genetics/Astellas; he reports receiving funding from AstraZeneca (Inst), Gilead Sciences, Ipsen, Merck Sharp & Dohme (Inst); he obtained honoraria from Astellas Pharma, AstraZeneca, Bristol Myers Squibb, Foundation Medicine, Janssen, Merck, Roche; he is currently employed by and has ownership interest in Bayer.