MP43-01 PHASE 2 KEYNOTE-057 STUDY: PEMBROLIZUMAB FOR PATIENTS WITH HIGH-RISK NON–MUSCLE INVASIVE BLADDER CANCER UNRESPONSIVE TO BACILLUS CALMETTE-GUERIN

You have accessJournal of UrologyBladder Cancer: Non-invasive III (MP43)1 Apr 2019MP43-01 PHASE 2 KEYNOTE-057 STUDY: PEMBROLIZUMAB FOR PATIENTS WITH HIGH-RISK NON–MUSCLE INVASIVE BLADDER CANCER UNRESPONSIVE TO BACILLUS CALMETTE-GUERIN Girish S. Kulkarini*, Ronald de Wit, Arjun V. Balar, Ashish Kamat, Edward Uchio, Loic Mourey, Laurence Krieger, Eric A. Singer, Dean Bajorin, Petros Grivas, Ho Kyung Seo, Hiroyuku Nishiyama, Badarinath Konety, Kijoeng Nam, Ekta Kapadia, Tara Frenkl, and Joost L. Boormans Girish S. Kulkarini*Girish S. Kulkarini* More articles by this author , Ronald de WitRonald de Wit More articles by this author , Arjun V. BalarArjun V. Balar More articles by this author , Ashish KamatAshish Kamat More articles by this author , Edward UchioEdward Uchio More articles by this author , Loic MoureyLoic Mourey More articles by this author , Laurence KriegerLaurence Krieger More articles by this author , Eric A. SingerEric A. Singer More articles by this author , Dean BajorinDean Bajorin More articles by this author , Petros GrivasPetros Grivas More articles by this author , Ho Kyung SeoHo Kyung Seo More articles by this author , Hiroyuku NishiyamaHiroyuku Nishiyama More articles by this author , Badarinath KonetyBadarinath Konety More articles by this author , Kijoeng NamKijoeng Nam More articles by this author , Ekta KapadiaEkta Kapadia More articles by this author , Tara FrenklTara Frenkl More articles by this author , and Joost L. BoormansJoost L. Boormans More articles by this author View All Author Informationhttps://doi.org/10.1097/01.JU.0000556224.50163.adAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVES: 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. Toronto, Canada; Rotterdam, Netherlands; New York, NY; Houston, TX; Orange, CA; Toulouse, France; St. Leonards, Australia; New Brunswick, NJ; New York, NY; Seattle, WA; Goyang, Korea, Republic of; Tsukuba, Japan; Minneapolis, MN; Kenilworth, NJ; Rotterdam, Netherlands© 2019 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 201Issue Supplement 4April 2019Page: e616-e616 Advertisement Copyright & Permissions© 2019 by American Urological Association Education and Research, Inc.MetricsAuthor Information Girish S. Kulkarini* More articles by this author Ronald de Wit More articles by this author Arjun V. Balar More articles by this author Ashish Kamat More articles by this author Edward Uchio More articles by this author Loic Mourey More articles by this author Laurence Krieger More articles by this author Eric A. Singer More articles by this author Dean Bajorin More articles by this author Petros Grivas More articles by this author Ho Kyung Seo More articles by this author Hiroyuku Nishiyama More articles by this author Badarinath Konety More articles by this author Kijoeng Nam More articles by this author Ekta Kapadia More articles by this author Tara Frenkl More articles by this author Joost L. Boormans More articles by this author Expand All Advertisement PDF downloadLoading ...

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.