A Single-arm Phase II Trial of Neoadjuvant Cabazitaxel and Cisplatin Chemotherapy for Muscle-Invasive Transitional Cell Carcinoma of the Urinary Bladder

Neoadjuvant cisplatin-based combination chemotherapy improves survival in muscle-invasive bladder cancer. However, response rates and survival remain suboptimal. We sought to evaluate the efficacy, safety and tolerability of cisplatin in combination with cabazitaxel in this patient group. This combination can be considered well-tolerated and efficacious with higher response rates (57.7%), which compares favorably to that with cisplatin/gemcitabine (23%-26%). 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 (p 0 = 0.35 and p 1 = 0.60, alpha = 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.