Shahrokh Shariat, MD
“BACILLUS CALMETTE-GUÉRIN (BCG) failures are quite common, with a 66% recurrence rate at 5 years, and about 25% of patients will have disease progression,” explained formal discussant Shahrokh Shariat, MD, Chair of the Department of Urology at Medical University, Vienna, and Adjunct Professor at Weill-Cornell Medicine, New York.
“Radical cystectomy, the treatment of choice for BCG failure, leads to excellent survival, but more than 60% of patients have significant morbidity, and 5% die within 90 days of surgery. In some cases, radical cystectomy is overtreatment. We need to do better where we can’t use BCG,” he told listeners. Currently approved drugs for intravesical salvage therapy are largely ineffective, he said, and delaying radical cystectomy could result in an increased mortality rate of about 20% of patients due to progression to muscle-invasive disease.
Potential Role for Checkpoint Inhibitors
“EMERGING DATA support a potential role for checkpoint inhibitors in non–muscle invasive bladder cancer. KEYNOTE-057 is the first study to use the right definition of adequate BCG, BCG-unresponsive, BCG-refractory, and BCG-relapsing patients, and therefore has not artificially enriched its population with ‘good players,’” he continued.
“Pembrolizumab is easier than radical cystectomy, and it is not more toxic. It has fewer complications and clinically acceptable efficacy. The complete response rate of 38.8% is the highest so far of any therapy, despite 30% of these patients harboring more aggressive disease than carcinoma in situ alone. None of the patients in whom pembrolizumab therapy failed experienced disease progression, so the window of opportunity for a curative intervention was preserved. Indeed, one could still salvage patients with radical cystectomy with curative intent,” Dr. Shariat said.
“The response rates in KEYNOTE-057 are encouraging, but we need more mature data with longer follow-up and phase III trials to determine the usefulness of pembrolizumab,” he stated. “We also need more biomarkers to identify patients who are most likely to benefit from a salvage systemic therapy such as pembrolizumab vs those who should undergo a radical cystectomy. The next threshold will be combining pembrolizumab with BCG. There are a lot of ongoing efforts to help these patients, including studies of avelumab (Bavencio), atezolizumab (Tecentriq), nivolumab (Opdivo), and durvalumab (Imfinzi),” he told listeners. He concluded that “high risk non–muscle invasive bladder cancer is the next frontier for checkpoint inhibitor strategies in bladder cancer care.” ■
DISCLOSURE: Dr. Shariat has received honoraria from, is a consultant or advisor for, and is on the speakers bureau for Astellas, AstraZeneca, Bayer, BMS, Cepheid, Ferring, Ipsen, Janssen Lilly, MSD, Olympus, Pfizer, Pierre Fabre, Roche, Sanochemia, Sanofi, Urogen, and Wolff. He also holds patents related to methods for detecting bladder cancer and for determining prognosis after treatment for bladder cancer.
THE ANTI–PROGRAMMED cell death protein 1 (anti–PD-1) checkpoint inhibitor pembrolizumab (Keytruda) was found to have antitumor activity in patients with high-risk non–muscle invasive bladder cancer who were nonresponsive to bacillus Calmette-Guérin (BCG), according to the preliminary results of the ...