On January 8, 2020, the FDA accelerated the approval of a new indication for pembrolizumab (Keytruda; Merck & Co) for the treatment of Bacillus Calmette-Guérin (BCG)-unresponsive, high-risk, non–muscle invasive bladder cancer and carcinoma in situ, with or without papillary tumors, in patients who are ineligible for or who have elected not to undergo cystectomy. Pembrolizumab has been previously approved for many indications.
The approval was based on efficacy results from the KEYNOTE-057 clinical trial, a multicenter, single-arm study involving 148 patients with high-risk non–muscle invasive bladder cancer, of whom 96 had BCG-unresponsive carcinoma in situ with or without papillary tumors. Patients received pembrolizumab 200 mg every 3 weeks until unacceptable toxicity, persistent or recurrent high-risk disease, or progressive disease, or up to 24 months of therapy without disease progression.
The major efficacy outcomes were complete response, urine cytology, computed tomography urography, and duration of response. The complete response rate in the 96 patients with high-risk BCG-unresponsive disease with carcinoma in situ was 41% (95% confidence interval, 31-51), and the median response duration was 16.2 months. Overall, 46% of responding patients had a complete response lasting ≥12 months.
The most common (≥10%) adverse reactions with pembrolizumab in this study were fatigue, diarrhea, rash, pruritis, musculoskeletal pain, hematuria, cough, arthralgia, nausea, constipation, urinary tract infection, peripheral edema, hypothyroidism, and nasopharyngitis.