PRM252 - SIMULATED TREATMENT COMPARISON: IMPLICATIONS AND CHALLENGES OF AN ALTERNATIVE APPROACH TO ESTIMATING THE RELATIVE EFFICACY OF NIVOLUMAB VERSUS RELEVANT COMPARATOR CHEMOTHERAPY TREATMENTS FOR ADVANCED/METASTATIC UROTHELIAL CARCINOMA IN THE UK

Abstract

The inability to derive relative efficacy estimates through head-to-head trials or traditional indirect treatment comparison is common in oncology. Here, a simulated treatment comparison (STC) was used to address this issue for the UK health technology assessment (HTA) of nivolumab for second-line advanced/metastatic urothelial carcinoma (UC) versus relevant comparator chemotherapy treatments (paclitaxel, docetaxel and best supportive care [BSC]) where only single-arm data were available. The STC was conducted in accordance with the National Institute for Health and Care Excellence (NICE) Decision Support Unit (DSU) Technical Support Document (TSD) 18. Individual patient-level data from the nivolumab CheckMate 275 and 032 trials were used to model survival outcomes based on key prognostic factors (e.g. performance status, liver metastases). This output was used to predict how patients in the comparator trials might respond to nivolumab. Survival outcomes were evaluated using a fractional polynomial network meta-analysis approach to estimate time-varying hazard ratios (HRs). Using a second-order fractional polynomial model with random effects (P1=1, P2=1), the HR for overall survival versus nivolumab increased over time from 0–96 weeks and was greater than 1 (favouring nivolumab) from 8 weeks for BSC and from 20 weeks for the other comparators. For progression-free survival, the second order fixed effects model (P1=1, P2=1) predicted HRs for progression versus nivolumab that varied considerably over time. The STC allowed the derivation of relative efficacy estimates between nivolumab and the relevant comparators as required for HTA. Despite the attempt to utilise the STC methodology as per NICE DSU guidance, UK HTA bodies criticised the implementation of the STC approach in this indication. Given the applicability of this challenge to many oncology indications, and the anticipated increase in single-arm trials, HTA bodies may need to issue clearer methodological guidance on the use of novel approaches such as STC for future appraisals.