Presentation Authors: Girish S. Kulkarini*, Toronto, Canada, Ronald de Wit, Rotterdam, Netherlands, Arjun V. Balar, New York, NY, Ashish Kamat, Houston, TX, Edward Uchio, Orange, CA, Loic Mourey, Toulouse, France, Laurence Krieger, St. Leonards , Australia, Eric A. Singer, New Brunswick, NJ, Dean Bajorin, New York, NY, Petros Grivas, Seattle, WA, Ho Kyung Seo, Goyang, Korea, Republic of, Hiroyuku Nishiyama, Tsukuba, Japan, Badarinath Konety, Minneapolis, MN, Kijoeng Nam, Ekta Kapadia, Tara Frenkl, Kenilworth, NJ, Joost L. Boormans, Rotterdam, Netherlands
Introduction: Most patients with non-muscle invasive bladder cancer (NMIBC) who receive standard-of-care TURBT and Bacillus Calmette-Guerin (BCG) experience recurrence. For BCG-unresponsive disease, radical cystectomy is the standard treatment option, though it is associated with significant morbidity and mortality. Upregulation of the PD-1 pathway has been observed in BCG-resistant NMIBC, suggesting that patients who receive PD-1/PD-L1 inhibitors may benefit. Efficacy and safety of the PD-1 inhibitor pembrolizumab as monotherapy in patients with high-risk (HR), BCG-unresponsive NMIBC were evaluated in the single-arm phase 2 KEYNOTE-057 study (NCT02625961); results for patients with carcinoma in situ (CIS) with or without papillary tumor (cohort A) are reported.
Methods: Patients were enrolled if they had histologically confirmed HR, BCG-unresponsive CIS with or without papillary disease and were unable or unwilling to undergo radical cystectomy. Patients received pembrolizumab 200 mg Q3W for 24 mo or until recurrence, progression, or unacceptable toxicity. Patients with HR NMIBC or progressive disease during treatment were required to discontinue. The primary end point was complete response (CR) rate, and key secondary end points were duration of response and safety.
Results: 103 pts (median age 73 years; CIS alone 71.8%; median number of prior BCG instillations 12) enrolled in cohort A. With a median follow-up of 14.0 mo (range 4.0-26.3), the 3-mo CR rate was 38.8% (95% CI 29.4%-48.9%) by central assessment. Among patients who achieved CR at 3 mo, median CR duration had not been reached (range 0+ to 14.1+ mo). 80.2% of patients had a CR duration of at least 6 mo (Kaplan-Meier method). 10 (25.0%) experienced recurrent NMIBC after CR; at the time of analysis, none progressed to muscle-invasive or metastatic disease. Treatment-related adverse events (AEs) occurred in 65 (63.1%) patients. Most frequent treatment-related AEs were pruritus (10.7%), fatigue (9.7%), diarrhea (8.7%), hypothyroidism (5.8%), and maculopapular rash (5.8%). Grade 3/4 treatment-related AEs occurred in 13 (12.6%) patients. 6 patients (5.8%) discontinued due to a treatment-related AE.
Conclusions: Pembrolizumab monotherapy had encouraging activity and a promising duration of response in patients with HR, BCG-unresponsive CIS with or without papillary tumors. The safety profile was consistent with that of previous experience. Updated data using additional follow-up will be presented.
Source of Funding: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.