The Bristol Bladder trial: A single-arm phase II trial of cisplatin and cabazitaxel for muscle invasive transitional cell carcinoma of the urinary bladder prior to radical cystectomy.

Authors

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Amit Bahl

Bristol Haematology and Oncology Centre, University Hospitals Bristol NHS Foundation Trust, Bristol, United Kingdom

Amit Bahl , Susan Masson , Amarnath Challapalli , Alicia Bravo , Sylvia Pearson , Serena Hilman , Raj Persad , Anthony Koupparis , Edward Rowe , Emily Foulstone , Heidi Evans , Jon Oxley , Rosemary Greenwood , Hannah Kirk , Rebecca Huckett , Julian Kabala , Janice Ash-Miles , Narges Dailami , Claire Perks , Jeff Holly

Organizations

Bristol Haematology and Oncology Centre, University Hospitals Bristol NHS Foundation Trust, Bristol, United Kingdom, University Hospital Bristol NHS Foundation Trust, Bristol, United Kingdom, University Hospitals Bristol NHS Foundation Trust, Bristol, United Kingdom, Urology, Bristol Royal Infirmary, Bristol, United Kingdom, North Bristol NHS Trust, Bristol, United Kingdom, University of West of England, Bristol, United Kingdom, University of Bristol, Bristol, United Kingdom

Research Funding

Pharmaceutical/Biotech Company

Background: Neoadjuvant cisplatin-based combination chemotherapy improves survival in muscle invasive transitional cell carcinoma (MI-TCC). However response rates and survival remain suboptimal. We sought to evaluate the efficacy of cabazitaxel (CBZ) with cisplatin (CIS) in this setting. Methods: A single arm phase 2 study was designed with 80% power to detect an objective response rate (ORR) of >35%. Patients with MI-TCC were included if fit to receive neoadjuvant chemotherapy and to undergo radical cystectomy. Treatment was with CIS 70mg/m2 and CBZ 15mg/m2 on day 1 of a 21 day cycle, for 4 cycles prior to surgery. Primary prophylaxis was with pegylated GCSF. Toxicity was recorded using CTCAE v.4.03. Objective response was defined as a reduction in Tumour (T) stage from T2 or greater at diagnosis, to T1 or less at radical cystectomy. QoL data was assessed during and after chemotherapy using EQ-5D and EORTC-BLM30 questionnaires. Results: 28 patients were enrolled with median age 68.6 years (range 47-79). Response outcome (first 23 cases) and toxicity data (first 24 cases) are in this abstract; the remaining cases, currently scheduled for surgery, will be added to the final presentation. Pathological complete response (pCR) was observed in 7/23 patients (30.4%) and ORR was 56.5% (13/23). 18/24 (75%) completed 4 cycles; reasons for stopping were disease progression (2/24, 8.3%), adverse events (2/24, 8.3%) and patient choice (2/24, 8.3%). 7/24 patients (29%) experienced treatment related grade 3 and 4 adverse events. Conclusions: These results demonstrate that CIS and CBZ chemotherapy has an acceptable safety profile and is well tolerated in this setting. This combination shows promising efficacy (pCR 30.4%, ORR 56.5%) prior to definitive treatment for MI-TCC. Response outcomes for all patients and QoL data will be reported in the final presentation. Grade 3/4 adverse events. Clinical trial information: NCT01616875

EventGraden/24 (%)
Neutropenia31 (4.2%)
Thrombocytopenia41 (4.2%)
Acute kidney injury32 (8.4%)
Urinary infection32 (8.4%)
Pyrexia31 (4.2%)
Fatigue31 (4.2%)
Raised liver enzymes31 (4.2%)
Pulmonary embolus31 (4.2%)
Enterovesical fistula31 (4.2%)

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Abstract Details

Meeting

2018 Genitourinary Cancers Symposium

Session Type

Poster Session

Session Title

Poster Session B: Prostate Cancer, Urothelial Carcinoma, and Penile, Urethral, and Testicular Cancers

Track

Urothelial Carcinoma,Prostate Cancer,Penile, Urethral, and Testicular Cancers

Sub Track

Urothelial Carcinoma

Clinical Trial Registration Number

NCT01616875

Citation

J Clin Oncol 36, 2018 (suppl 6S; abstr 468)

DOI

10.1200/JCO.2018.36.6_suppl.468

Abstract #

468

Poster Bd #

H17

Abstract Disclosures