Patients With High-Risk Non-Muscle Invasive Bladder Cancer Show Response to Keytruda

Patients with high-risk non-muscle invasive bladder cancer (NMIBC) have potential new hope in the immunotherapy drug Keytruda (pembrolizumab). An interim analysis showed that 38.8 percent of patients had no signs of disease at three months after not responding to standard of care.

The phase 2 trial, KEYNOTE-057, examined the use of Keytruda alone in previously-treated patients with NMIBC with carcinoma in situ (CIS; a group of abnormal cells) or CIS plus papillary disease who either were ineligible for or refused to undergo radical cystectomy.

The trial was broken into two groups with different primary endpoints: group A (130 participants) evaluating complete response (showing no signs of disease following treatment) and group B (130 participants) evaluating disease-free survival.

The interim data presented at the 2018 ESMO Congress in Munich, Germany, was from 103 of the 130 patients in group A. Researchers reported a complete response in 40 patients, with 80 percent having a complete response that lasted six months or longer. Fifty-seven patients (55.3 percent) did not achieve complete response — patients had either persistent disease, NMIBC stage progression or extravesical disease.

At the time of analysis, 72.5 percent of responding patients had an ongoing response and 25 percent experienced recurrent disease. One patient discontinued treatment and started alternative therapy. The median follow-up was 14 months.

“The nearly 40 percent complete response rate with Keytruda in patients with high-risk non-muscle invasive bladder cancer is encouraging and adds to the growing body of data showing the anti-tumor activity of Keytruda as monotherapy across different types of cancer,” Scot Ebbinghaus, M.D., vice president of clinical research at Merck Research Laboratories, said in a press release from Merck, the drug’s manufacturer.

Nearly all patients (96.1 percent) experienced at least one side effect. But they were consistent with what has been seen in previous Keytruda trials, according to researchers. The most common treatment-related side effects were chronic itchy skin (10.7 percent), fatigue (9.7 percent), diarrhea (8.7 percent), hypothyroidism (5.8 percent) and red, bumpy rash (5.8 percent). Grade 3/5 side effects occurred in 13 patients (12.6 percent). The most common grade 3/5 treatment-related side effects included low sodium levels (2.9 percent) and joint pain (1.9 percent). Three patients died — one related to treatment and two unrelated to bladder cancer.

This year, nearly 550,000 new cases of bladder cancer will be diagnosed, according to the World Cancer Research Fund. And 80 percent of patients with bladder cancer are diagnosed with NMIBC, which occurs when the cancer has not grown into the main muscle layer of the bladder.

“Treatment options for high-risk non-muscle invasive bladder cancer have historically been limited, with many patients relying on surgery as their only option following disease recurrence,” Ronald de Wit, M.D., Ph.D., group leader of experimental systemic therapy of urogenital cancers at Erasmus MC Cancer Institute in Rotterdam, The Netherlands, said in a press release.

“Additionally, about 40 percent of patients with high-risk non-muscle invasive bladder cancer progress to muscle invasive disease,” he added. “These data from KEYNOTE-057 are encouraging for patients with this hard-to-treat form of bladder cancer who are ineligible for surgery.”