Pembrolizumab active in non-muscle-invasive bladder cancer unresponsive to BCG
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SAN FRANCISCO — Pembrolizumab monotherapy exhibited antitumor activity among certain patients with high-risk non-muscle-invasive bladder cancer, according to results of a single-arm phase 2 study.
The findings — presented at ASCO Genitourinary Cancers Symposium — highlighted the agent’s potential benefit among patients with papillary tumors without carcinoma in situ who did not respond to bacillus Calmette-Guèrin (BCG) therapy.
“I am pretty confident that we can at least rediscuss the way of conceiving new therapies in papillary tumors and potentially overcoming the need for limitations of a randomized study in this very-difficult-to-treat patient population, because we do not have reliable data with standard-of-care therapies,” Andrea Necchi, MD, director of genitourinary medical oncology at IRCCS San Raffaele Hospital and Scientific Institute and associate professor at Vita-Salute San Raffaele University in Italy, told Healio.
Background and methodology
Standard of care for high-risk non-muscle-invasive bladder cancer includes BCG.
The prognosis for patients who do not respond to this treatment, or who relapse within 12 months, is poor. These patients often undergo radical cystectomy, according to study background.
The single-arm, multicenter phase 2 KEYNOTE-057 trial included 132 patients (median age 72, range 37-87; 78.8% men) with high-risk non-muscle-invasive bladder cancer whose cancer did not respond to BCG. All patients either were ineligible for or had declined cystectomy.
Patients received 200 mg pembrolizumab (Keytruda, Merck) every 3 weeks. Treatment continued for up to 24 months, or until unacceptable toxicity, persistent or recurrent high-risk disease, or progressive disease.
Patients underwent disease assessments at 12 weeks and 24 weeks.
Twelve-month DFS for high-risk non-muscle-invasive bladder cancer and safety served as the primary endpoints. Secondary endpoints included 12-month DFS for any disease, as well as PFS and OS.
Results
Patients received pembrolizumab monotherapy for a median 9.5 cycles (range, 1-35). Median follow-up was 45.4 months (range, 14.9-77.1)
Researchers reported a median DFS for high-risk non-muscle-invasive bladder cancer of 7.7 months (95% CI, 5.5-13.6). Researchers reported DFS rates of 43.5% (95% CI, 34.9-51.9) at 12 months, and 34.9% at both 24 months and 36 months.
Results showed median DFS for any disease of 6 months (95% CI, 4.3-12), with a 12-month DFS rate of 41.7% (95% CI, 33.1-50).
Median PFS defined as time to worsening of grade, worsening of stage or death was 44.5 months (95% CI, 34.6-not available). Median PFS defined as time to muscle invasion, metastasis or death was 46.2 months (95% CI, 36.8-not available).
Median OS had not been reached; however, nearly all (96.2%; 95% CI, 91.1-98.4) patients survived at least 12 months.
Ninety-seven patients (73.5%) experienced treatment-related adverse events. Nineteen (14.4%) experienced grade 3/grade 4 treatment-related adverse events, and 14 (10.6%) discontinued therapy due to a treatment-related adverse event. No deaths due to treatment-related adverse events occurred.
Next steps
Pembrolizumab monotherapy appears to have significant potential for this patient population, Necchi said.
“I think we can rediscuss ... the possibility of extending the indication for pembrolizumab [among patients with] higher-risk disease [who] are nonresponsive to bacillus Calmette-Guérin,” Necchi told Healio.
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Necchi A, et al. Abstract LBA442. Presented at: ASCO Genitourinary Cancers Symposium; Feb. 16-18, 2023: San Francisco.
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