Abstract: PD19-08
Sources of Funding: Cancer Research UK funded the trial administration (trial number CRUK/09/012). Kyowa Hakko UK Ltd kindly gave the trial a total of GBP75,000 which helped to fund the procurement and maintenance costs of the Synergo system. Medical Enterprises Europe B.V. supplied the Synergo system at a discounted rate and its associated disposables to the participating sites. All funders had no role in the study design, data collection, data analysis, data interpretation, writing of the report and in the decision to submit the paper for publication. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.

Introduction

Despite maintenance BCG, ≥50% of patients will develop bladder cancer recurrence and 10-20% will progress within 52 months. There is no effective second-line therapy for NMIBC following BCG failure. The combination of intravesical mitomycin-C (MMC) with RITE has shown efficacy when compared to BCG. This study aims to determine whether RITE improves disease-free survival (DFS) compared to standard of care in patients with recurrence of NMIBC following BCG.

Methods

This multicentre, open-label, phase III randomised controlled trial was performed in 14 UK centres (ClinicalTrials.gov: NCT01094964). Patients with NMIBC who developed recurrence following BCG induction/ maintenance therapy were randomly assigned (1:1) to either RITE (60 min, 40 mg mitomycin-C at 42°C) using the Synergo® SB-TS 101 System or a second course of BCG/ institutional standard. All patients had complete resection of papillary visible tumours and must be either unfit or unwilling to have radical cystectomy. Randomisation was stratified by centre, CIS and prior BCG response. Primary outcomes were DFS and complete response (CR) at three months in patients with CIS at randomisation. A log-rank test was performed to compare arms on an intention-to-treat basis.

Results

Between May 2010 and July 2013, 104 patients were randomised. 48 (46%) assigned to RITE and 56 (54%) control. Median DFS was 35.1 months (IQR: 23.1-445.3 months) with no difference between treatment arms (HR 1.32, [0.83-2.1], p=0.23). Three-month CR in CIS patients for both treatment arms were similar (RITE: 75% vs control: 80%, p=0.62). DFS in patients with papillary-only disease was higher in RITE patients (HR 0.42, [0.19-1.03], p=0.0531) but not significantly different in CIS-only patients (HR 1.61, [0.8-3.2], p=0.17). Papillary disease and concurrent CIS patients had significantly better DFS in the control arm (HR 6.9, [2.06-23.25], p<0.001). No difference in adverse events between treatment arms were observed.

Conclusions

The HYMN trial did not show an overall difference between RITE and the control arm. However, there was a benefit for RITE in participants with papillary-only disease. RITE was well tolerated with comparable adverse events compared with BCG. Further trials are needed to investigate the efficacy of RITE in CIS patients.

Funding

Cancer Research UK funded the trial administration (trial number CRUK/09/012). Kyowa Hakko UK Ltd kindly gave the trial a total of GBP75,000 which helped to fund the procurement and maintenance costs of the Synergo system. Medical Enterprises Europe B.V. supplied the Synergo system at a discounted rate and its associated disposables to the participating sites. All funders had no role in the study design, data collection, data analysis, data interpretation, writing of the report and in the decision to submit the paper for publication. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.