A single arm phase II trial of neoadjuvant cabazitaxel and cisplatin chemotherapy for muscle invasive transitional cell carcinoma of the urinary bladder

Challapalli, Amarnath; Masson, Susan; White, Paul; Dailami, Narges; Pearson, Sylvia; Rowe, Edward; Koupparis, Anthony; Oxley, Jon; Abdelaziz, Ahmed; Ash-Miles, Janice; Bravo, Alicia; Foulstone, Emily; Perks, Claire; Holly, Jeff; Persad, Raj; Bahl, Amit

Abstract

Introduction: Neoadjuvant cisplatin-based combination chemotherapy improves survival in muscle-invasive bladder cancer. However, response rates and survival remain suboptimal. We evaluated the efficacy, safety, and tolerability of cisplatin plus cabazitaxel. Methods: A phase II single-arm trial was designed to recruit at least 26 evaluable patients. This would give 80% power to detect the primary endpoint, an objective response rate defined as a pathologic complete response plus partial response (pathologic downstaging), measured by pathologic staging at cystectomy (p0 = 0.35 and p1 = 0.60, α = 0.05). Results: Objective response was seen in 15 of 26 evaluable patients (57.7%) and more than one- third of patients achieved a pathologic complete response (9/26; 34.6%). Seventy-eight percent of the patients (21/27) completed all cycles of treatment, with only 6.7% of the reported adverse events being graded 3 or 4. There were 6 treatment-related serious adverse event reported, but no suspected unexpected serious adverse reactions. In the patients who achieved an objective response, the median progression-free survival and overall survival were not reached (median follow-up of 41.5 months). In contrast, the median progression-free survival (7.2 months) and overall survival (16.9 months) were significantly worse (P = .001, log-rank) in patients who did not achieve an objective response. Conclusion: Cabazitaxel plus cisplatin for neoadjuvant treatment of muscle-invasive bladder cancer can be considered a well-tolerated and effective regimen before definitive therapy with higher rates (57.7%) of objective response, comparing favorably to that with of cisplatin/gemcitabine (23%–26%). These results warrant further evaluation in a phase III study.

• Journal Article Type: Article
• Acceptance Date: Feb 13, 2021
• Online Publication Date: Feb 17, 2021
• Publication Date: Aug 1, 2021
• Deposit Date: Feb 14, 2021
• Publicly Available Date: Feb 18, 2022
• Journal: Clinical Genitourinary Cancer
• Print ISSN: 1558-7673
• Electronic ISSN: 1938-0682
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 19
• Issue: 4
• Pages: P325-332
• DOI: https://doi.org/10.1016/j.clgc.2021.02.001
• Keywords: Neoadjuvant chemotherapy; Pathologic complete response; Bladder cancer; Radical cystectomy; Adverse events
• Public URL: https://uwe-repository.worktribe.com/output/7094593