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 evaluated the efficacy, safety, and tolerability of cisplatin plus cabazitaxel.

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).

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.

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.

Clinical genitourinary cancer. 2021 Feb 18 [Epub ahead of print]

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

Department of Clinical Oncology, Bristol Cancer Institute, Bristol, UK., Department of Statistics, University of the West of England, Bristol, UK., Department of Urology, Bristol Urological Institute, North Bristol NHS Trust, Bristol, UK., Department of Pathology, North Bristol NHS Trust, Bristol, UK., Department of Oncology, Ain Shams University Hospitals, Egypt., Department of Radiology, North Bristol NHS Trust, Bristol, UK., IGFs & Metabolic Endocrinology Group, Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK., Department of Clinical Oncology, Bristol Cancer Institute, Bristol, UK. Electronic address: .

Read an Expert Commentary by Bishoy Faltas, MD