Pembrolizumab (pembro) for the treatment of patients with Bacillus Calmette-Guérin (BCG) unresponsive, high-risk (HR) non–muscle-invasive bladder cancer (NMIBC): Over two years follow-up of KEYNOTE-057.

Abstract

5041 Background: Pembro was recently approved for the treatment of HR NMIBC based on results from the phase 2 KEYNOTE-057 (NCT02625961) study. Herein we present safety, efficacy, and posttreatment outcomes with > 2 y follow-up from KEYNOTE-057 cohort A. Methods: Patients with histologically confirmed HR BCG-unresponsive carcinoma in situ (CIS) with or without papillary tumors who received adequate BCG therapy and were ineligible for or opted out of radical cystectomy (RC) received pembro 200 mg Q3W for up to 2 y or until disease recurrence, progression, or unacceptable toxicity. The primary end point was complete response rate (CRR). Key secondary end points were duration of response (DOR) and safety. Results: Overall, 102 patients were initially enrolled, and 96 were included in the efficacy analysis. Median time from enrollment to data cut off was 28.4 months (range, 18.2-40.5). CRR was 40.6% (95% CI, 30.7-51.1), and median DOR was 16.2 months (range, 0+ to 30.4+). Among 39 patients with CR, 18 (46.2%) had a DOR ≥12 months. No patient’s disease progressed to muscle-invasive or metastatic bladder cancer while on study treatment. Median PFS and OS were not reached. At 12 months, PFS was 82.7% and OS was 97.9%. A total of 36 patients (37.5%) underwent RC after discontinuation from study treatment, which included 9 of 22 patients (40.9%) who had recurrence after initial CR and 27 of 57 (47.4%) nonresponders. Of the 36 who underwent RC, 33 (91.6%) had no pathological upstaging to MIBC and 3 (8.3%) had at least pT2 disease at time of RC. For subsequent treatments other than RC, 27 of 96 (28.1%) patients received additional intravesical therapy (eg, BCG, gemcitabine, or mitomycin), 21 of 96 (21.9%) underwent local procedures (eg, TURBT), and 3 of 96 (3.1%) received systemic therapy (eg, pembro). In 102 patients treated with pembro, treatment-related AEs (TRAEs) occurred in 67 (65.7%) patients; most frequently reported TRAEs were fatigue, pruritus, and diarrhea (10.8% each). Grade 3/4 TRAEs occurred in 13 patients (12.7%), and 21 patients (20.6%) experienced immune-mediated AEs. There were no grade 5 TRAEs. Conclusions: After > 2 y of follow-up, durable and clinically meaningful activity of pembro was observed in patients who had HR BCG-unresponsive CIS with or without papillary tumors and who were ineligible for or opted out of RC. Pembro did not seem to limit the opportunity for subsequent therapies, including RC. The safety profile was consistent with what is reported in the literature. Clinical trial information: NCT02625961 .