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

Abstract Purpose : Neoadjuvant cisplatin-based combination chemotherapy improves survival in muscle invasive bladder cancer (MIBC). 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. Methods : A phase II single arm trial was designed (Simon-2 stage), to recruit at least 26 evaluable patients. This would give 80% power to detect the primary endpoint, objective response rate (ORR) defined as pathological complete response (pCR) plus partial response (pathological downstaging), measured by pathologic staging (T stage) at cystectomy (p0 =0.35 and p1 =0.60, α =0.05). Results : Objective response was seen in 15 out of 26 evaluable patients, 57.7% and over a third of patients achieved pCR (9/26; 34.6%). 78% (21/27) of patients completed all cycles of treatment, with only 6.7% of the reported adverse events (AEs) being graded 3 or 4. There were 6 treatment related SAEs reported but no SUSARs. In the patients who achieved objective response, the median progression-free (PFS) and overall survival (OS) were not reached (median follow-up of 41.5m). In contrast the median PFS (7.2m) and OS (16.9m) were significantly worse (p=0.001, log-rank) in patients who did not achieve objective response. Conclusion : Cabazitaxel in combination with cisplatin for neoadjuvant treatment of MIBC can be considered a well-tolerated and effective regimen prior to definitive therapy with higher rates (57.7%) of objective response, which compares favorably to that with Cisplatin/Gemcitabine (23-26%). These results warrant further evaluation in a phase-3 study.