Geographic transferability of health economic analyses (HEA) may be facilitated by addressing differences in treatment and patient characteristics of an original trial population vs the population of interest. For a health technology assessment–driven HEA, applicability of the FIRE-3 trial comparing cetuximab to bevacizumab added to FOLFIRI (CET+F; BEV+F) as first-line treatment of RAS wild-type metastatic colorectal cancer was explored. In FIRE-3, a proportion of patients received panitumumab (PAN) as a subsequent treatment. Treatment-switching analyses were used to adjust overall survival (OS) for later-line treatment effects in jurisdictions where PAN is unavailable.
The two-stage method (TSM) was applied to adjust trial outcomes. In scenario analyses, excluding (EXC) or censoring (CEN) PAN-receiving patients from FIRE-3 OS was explored. TSM adjusts patients’ survival times (ST) by multiplying ST beyond start of second-line treatment with an acceleration factor (AF), which represents relative effectiveness of PAN vs other subsequent treatments (first step). AFs were derived from the FIRE-3 trial (internal [INT]) and external (EXT) published data. Resulting counterfactual ST estimates were calculated for each patient according to the first-line treatment received (second step). Recensoring was applied to correct for imbalances resulting from AF <1. Counterfactual ST were compared, and hazard ratios (HRs) were calculated for each method. Bootstrap analyses were performed to estimate uncertainty over the outcomes.
The FIRE-3 trial HR (95% CI) for CET+F vs BEV+F was 0.697 (0.539-0.903). HRs adjusted for subsequent PAN use were 0.682 (0.526-0.885; TSM INT), 0.696 (0.530-0.914; TSM EXT), 0.702 (0.531-0.929; EXC), and 0.714 (0.540-0.944; CEN). P-values for all HRs were ≤0.05.
Adjusted HRs showed OS improvement favouring CET+F. Bootstrap analyses confirmed deterministic results. Consequently, data from the FIRE-3 trial can be applied in HEA in a range of jurisdictions to calculate robust ICERs for CET+F vs BEV+F.
© 2020 Published by Elsevier Inc.