Matching Adjusted Indirect Comparison (MAIC) in RET-Mutation Positive Medullary Thyroid Cancer (MTC)




Conducting comparative effectiveness research is challenging in the absence of direct head-to-head trials and are complicated with data from single-arm trials and when patient-level data are not available from all comparators. An unanchored MAIC was conducted comparing the single-arm LIBRETTO-001 (selpercatinib) trial with summary data from the EXAM trial (cabozantinib and placebo) in advanced/metastatic MTC.


Progression free and overall survival (PFS, OS) were adjusted using propensity-score weighting. Patient-level data from LIBRETTO-001 were matched to digitized curve data from the EXAM trial. PFS curve data were available for the RET-positive cohort but OS was only provided forthe RET M918T subgroup in EXAM. Cohorts were all RET mutation+ and were balanced on all available covariates (age, weight, performance status, sex, smoking status, prior tyrosine kinase inhibitor therapy, and RET M918T mutation status). Since only summary statistics for baseline characteristics were available from the EXAM study, an unanchored MAIC model was applied and a weighted Cox model was conducted in R.


Before weighting, all comparisons were highly statistically significant (all p<0.001). After weighting, the PFS hazard ratio (HR) versus cabozantinib was 0.15 (95% CI:0.09,0.24;p<0.001) and versus placebo 0.06 (95% CI:0.04,0.10;p<0.001). The selpercatinib OS HR was 0.25 (95% CI:0.12,0.54; p=0.002) and 0.11 (95% CI:0.05,0.24;p<0.001) versus cabozantinib and placebo, respectively.


In both a naïve comparison and an unanchored MAIC, selpercatinib demonstrated a significant improvement in PFS and OS versus cabozatinib and versus placebo. This study is limited by the lack of randomized trials comparing selpercatnib vs cabozantinib and the limited number of covariates available for inclusion. As a result, there is a risk of unmeasured confounding that could influence these findings. While best practices were followed to ensure the comparisons were conducted in accordance with NICE Guidelines, these findings must be interpreted with caution considering the limitations of an unanchored MAIC.

Conference/Value in Health Info

2021-05, ISPOR 2021, Montreal, Canada

Value in Health, Volume 24, Issue 5, S1 (May 2021)




Clinical Outcomes

Topic Subcategory

Comparative Effectiveness or Efficacy



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