The FDA has approved the anti-PD-1 therapy pembrolizumab (KEYTRUDA) as monotherapy for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, nonmuscle-invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.
The approval was based on data from the multicenter, open-label KEYNOTE-057 trial in 96 patients. Patients received pembrolizumab, 200 mg every 3 weeks. At a median follow-up of 28 months, pembrolizumab demonstrated a complete response rate of 41%. Among the 39 patients who achieved a complete response, the median duration of response was 16.2 months, and 46% had a response of 12 months or longer.
“Historically, patients with high-risk, nonmuscle-invasive bladder cancer with CIS whose cancer is unresponsive to BCG treatment had limited non-surgical treatment options. As a physician who specializes in the management of bladder cancer, it is encouraging to now have a new treatment option for these patients,” said KEYNOTE-057 lead investigator Arjun V. Balar, MD, of NYU Langone Health’s Perlmutter Cancer Center, New York.
Pembrolizumab was discontinued due to adverse reactions in 11% of patients in KEYNOTE-057. The most common adverse reaction (>1%) resulting in its permanent discontinuation was pneumonitis (1.4%). Adverse reactions leading to interruption of pembrolizumab occurred in 22% of patients; the most common (≥2%) were diarrhea (4%) and urinary tract infection (2%). Serious adverse reactions occurred in 28% of pembrolizumab -treated patients. The most frequent serious adverse reactions (≥2%) were pneumonia (3%), cardiac ischemia (2%), colitis (2%), pulmonary embolism (2%), sepsis (2%), and urinary tract infection (2%). The most common adverse reactions (≥20%) were fatigue (29%), diarrhea (24%), and rash (24%).