OBJECTIVES: This study compared the cost-effectiveness, from the US Medicare perspective, of tyrosine kinase inhibitors tepotinib and capmatinib for treating line-agnostic adult patients with metastatic non-small cell lung cancer (mNSCLC) harboring mesenchymal-epithelial transition factor gene exon 14 (METex14) skipping alterations.

METHODS: A de novo three-state partitioned survival model was used to assess outcomes in the target population over a lifetime (20-year) horizon. Overall and progression-free survival and time to treatment discontinuation (TTD) for tepotinib were based on a parametric survival analysis of the Phase II VISION trial (February 2021 data cut-off). Capmatinib outcomes were captured using hazard ratios derived from a matching-adjusted indirect comparison study or published literature. Drug acquisition/administration, treatment monitoring, and disease and adverse event management expenditures were obtained from US national cost databases (IBM Micromedex^® Redbook^®, InHealth Professional Services, CMS.gov, HCUP.net) or published literature. Utility inputs were collected from clinical trial data and the literature. Uncertainty on key parameters and structural assumptions were explored through deterministic and probabilistic sensitivity analyses (DSA/PSA) and scenario analyses.

RESULTS: Compared to capmatinib, tepotinib yielded an additional 0.4080 life-years, 0.2872 quality-adjusted life-years (QALYs), and incremental costs of $30,223 (driven by increased monthly drug costs and longer treatment duration of tepotinib), culminating in an incremental cost-effectiveness ratio (ICER) of $105,235/QALY. This compared favorably with the Institute for Clinical and Economic Review’s current “health-benefit price benchmark” of $100,000-150,000/QALY. The DSA suggested results were sensitive to TTD and drug acquisition costs, whereas the PSA supported the base case results. Scenario analyses exploring shorter time horizons (5 and 10 years), alternative payer perspectives (Medicaid), cost-sharing mechanisms ($35 co-payment and 10% co-insurance), and published sources for utility weights produced ICERs from $97,825 to $121,198.

CONCLUSIONS: From the US Medicare perspective, tepotinib could be cost-effective relative to capmatinib in treating patients with mNSCLC harboring METex14 skipping alterations.