FDA advisory committee supports approval of Keytruda for high-risk bladder cancer
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An FDA advisory committee today voted to support approval of pembrolizumab for the treatment of patients with bacillus Calmette-Guérin-unresponsive, high-risk, nonmuscle-invasive bladder cancer with carcinoma in situ with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.
The final vote of 9-4 by the Oncologic Drugs Advisory Committee reflected the panel’s confidence in the safety and efficacy of pembrolizumab (Keytruda, Merck) for this indication despite a lack of phase 3 randomized trials. The panel also debated the use of complete response rate and duration of response as trial endpoints to support the agent’s efficacy.
“I voted yes because the drug is safe and it seems to be effective for these patients and has a role for treatment in a very specific situation,” Christian Hinrichs, MD, clinical researcher at NCI Center for Cancer Research, said after the vote. “I also have a lot of confidence in the physicians who are counseling these patients to present this as an option and in the context of what’s known and what’s not known.”
Results from the phase 2, single-arm KEYNOTE-057 trial, presented at Genitourinary Cancers Symposium in February, showed that pembrolizumab induced durable complete responses among patients with high-risk, nonmuscle-invasive, bacillus Calmette-Guérin (BCG)-unresponsive bladder carcinoma in situ with or without papillary tumors.
These results led to the FDA granting priority review to the supplemental biologics license application for pembrolizumab.
The trial included 102 patients (median age, 73 years) who received adequate BCG therapy and could not or did not wish to undergo radical cystectomy.
Patients received 200 mg pembrolizumab every 3 weeks for 24 months or until recurrence, progression or unacceptable toxicity.
Overall, 40.2% (95% CI, 30.6-50.4) of the trial population achieved complete response.
Median follow-up for patients in complete response was 16.7 months (range, 5.9-28.2).
Of these 41 responding patients, 24 (58.5%) had an ongoing response at the time of data cutoff.
Updated data included in background documents presented to the advisory committee showed median duration of response of 16.2 months (range, 1 day+ to 30 months+), and 48% of responding patients maintained their response for at least 1 year, representing 20% of all treated patients.
Thirty-eight patients who did not achieve complete response or who developed recurrence after complete response underwent subsequent cystectomy. Three of these patients (8%) developed muscle-invasive disease.
The most common adverse events in the trial included diarrhea, fatigue, hematuria, pruritis and cough. Twenty-nine percent of patients experienced grade 3 to grade 4 adverse events, the most common of which included pneumonia, hyperglycemia, hyponatremia, pulmonary embolism, urinary tract infection, arthralgia and cellulitis.
Not all panelists were convinced that the efficacy data were sufficient for approval.
“I struggled with this because my patients need better treatments,” Andrea Apolo, MD, NIH Lasker Clinical Research Scholar at NCI, said after the vote. “But the data are still too early and we need more follow-up in order to put this is in as a standard treatment option for these patients.”– by John DeRosier
Reference:
Balar AV, et al. Abstract 350. Presented at: Genitourinary Cancers Symposium; Feb. 14-16, 2019; San Francisco.