Immunotherapy Receives FDA Approval for High-Risk, BCG-Unresponsive, Non-Muscle-Invasive Bladder Cancer

On 8 January 2020, the US Food and Drug Administration (FDA) approved pembrolizumab (Keytruda) immunotherapy for Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle-invasive carcinoma in situ (CIS), with or without papillary tumors, in bladder cancer patients ineligible for or declining surgery.

This was the first approval for new-generation immune checkpoint inhibitor immunotherapiesat the earliest cancer stage, with wide-ranging implications for treatment.

The multicenter single-arm trial KEYNOTE-057enrolled high-risk non-blood-layer-invasive bladder cancer in 148 patients, of whom 96 had BCG-unresponsive CIS with or without papillary tumors. All received treatment every 3 weeks with 200 mg pembrolizumab, until unacceptable toxicity, persistent, recurrent, or progressive disease, or otherwise up to 24 months.

The main efficacy endpoints were complete response and duration. Complete response was assessed by cystoscopy, imaging and sampling with a thin camera-tipped tube, urine cytology, cellular analysis, and computed tomography.

Among 96 BCG-unresponsive patients, %41 achieved complete response with median duration 16.2 months. Among responders, % 46 maintained complete response for at least 12 months.

In KEYNOTE-057, the most common (≥% 10) adverse effects were fatigue, diarrhea, rash, itching, musculoskeletal pain, hematuria, cough, arthralgia, joint pain, nausea, constipation, urinary infection, peripheral edema, hand and foot swelling, hypothyroidism, low thyroid hormones, and nasopharyngitis, upper respiratory infection. Recommended pembrolizumab dose is every 3 weeks, 200 mg.