On January 8, 2020, the FDA approved pembrolizumab (Keytruda; Merck) for the treatment of patients with Bacillus Calmette-Guérin (BCG)-unresponsive, high-risk, non–muscle-invasive bladder cancer with carcinoma in situ with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy. Keytruda has received previous FDA approval as a single agent or in combination with other agents for the treatment of many types of cancers.
This new indication was based on results of KEYNOTE-057, a multicenter, single-arm, clinical trial of 148 patients with high-risk, non–muscle-invasive bladder cancer; 96 of whom had BCG-unresponsive carcinoma in situ with or without papillary tumors. Patients were treated with 200 mg of pembrolizumab every 3 weeks until unacceptable toxicity; persistent or recurrent high-risk, non–muscle-invasive bladder cancer or progressive disease; or up to 24 months of therapy without disease progression.
The major efficacy outcome measures in the trial were complete response (CR), defined by negative results for cystoscopy (with transurethral resection of bladder tumor/biopsies as applicable, urine cytology, and computed tomography urography imaging) and duration of response. Median follow-up was 28.0 months.
Treatment with pembrolizumab resulted in a CR rate of 41% in the 96 patients with high-risk BCG-unresponsive non–muscle-invasive bladder cancer with carcinoma in situ. Among the 39 patients who achieved a CR, median duration was 16.2 months, and 46% had a response lasting ≥12 months.
The most common (≥20%) adverse reactions in patients treated with pembrolizumab in the KEYNOTE-057 trial were fatigue, diarrhea, rash, pruritis, musculoskeletal pain, hematuria, cough, arthralgia, nausea, constipation, urinary tract infection, peripheral edema, hypothyroidism, and nasopharyngitis.