The FDA approved pembrolizumab (Keytruda) for the treatment of patients with Bacillus Calmette-Guerin (BCG)–unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in-situ (CIS) with or without papillary tumors who are ineligible for or chose to not undergo cystectomy.1
This approval follows a 9-4 favorable vote from the agency’s Oncologic Drugs Advisory Committee (ODAC) supporting the approval of the new drug application for the drug.2
The FDA based its decision on results from the multicenter, open-label, single-arm, multicohort phase II KEYNOTE-057 trial (NCT02625961) – which enrolled 02 patients with BCG-unresponsive, high-risk, NMIBC with CIS with or without papillary tumors who were ineligible for or did not undergo cystectomy (cohort A). Cohort B of the study consists of 130 patients with papillary disease without CIS.
Pembrolizumab was administered at 200 mg every 3 weeks until unacceptable toxicity, persistent or recurrent high-risk NMIBC, or disease progression. Disease was assessed every 12 weeks, and those who did not have disease progression could receive treatment for up to 2 years. The primary outcome measures were CR, urine cytology, and computed tomography urography imaging, and duration of response.
In cohort A, 97 patients treated with pembrolizumab elicited a 41.2% (95% CI, 31.5-51.4) complete response (CR) rate and a median duration of CR of 16.2 months (range, 0.0+ to 26.8+). Nineteen (48%) of the 40 responding patients maintained their response for 1 year or more.
At an updated median follow-up of 21.1 months (range, 4.6-33.4), treatment was ongoing in 11 patients. Eighty-eight patients discontinued pembrolizumab due to persistent disease (n = 40), recurrent disease (n = 33), adverse events (AEs; n = 10), achieved CR (n = 2), physician decision (n = 1), protocol violation (n = 1), and patient withdrawal (n = 1).
The most common AEs (incidence ≥10%) were fatigue, diarrhea, rash, pruritis, musculoskeletal pain, hematuria, cough, arthralgia, nausea, constipation, urinary tract infection, peripheral edema, hypothyroidism, and nasopharyngitis.
The FDA recommended a dose of 200 mg pembrolizumab every 3 weeks.
1. Food and Drug Administration. FDA approves pembrolizumab for BCG-unresponsive, high-risk non-muscle invasive bladder cancer. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-appro.... Accessed January 8, 2020.
2. PEMBROLIZUMAB-P057V01MK3475 Advisory Committee Briefing Document. FDA. https://www.fda.gov/media/133542/download. Accessed December 17, 2019.