Background: The Enhancing Oncology Model (EOM) is a voluntary two-sided risk model that compares practice expenditures relative to calculated benchmarks for seven cancer types. To account for changes in cancer costs based on clinical characteristics, the EOM applies metastatic (M0 vs. M1) and HER2 clinical adjustments. These adjustments modify lung and small intestine/colorectal episodes for ever-metastatic status by a factor of 1.06 and 1.10, respectively, and breast cancer episodes by a factor of 1.23 for ever-metastatic status and HER2 positivity. However, it is unclear how well these methodological additions capture indication-specific treatment costs of care within an EOM disease group. Methods: Medicare Part B Drug and Biological Average Sales Price (ASP) data were analyzed to estimate total cost to Medicare for a six-month course of systemic therapy within three common EOM disease groups: breast cancer, lung cancer, and colorectal cancer. Diseases were further broken down by M0 vs. M1 and HER2 status consistent with EOM methodology. All treatment regimens selected for analysis are concordant with National Comprehensive Cancer Network guidelines and considered standard of care based on clinical phenotypes – including PD-L1 status, lymph node status, and tumor size – which are not captured by EOM methodology. Results: Within common EOM disease groups and after accounting for EOM clinical adjusters, six-month episode costs of standard of care systemic treatments vary widely based on clinical features not captured in the model. For instance, the cost of care from drug treatment alone varies by over 220-fold for M0 NSCLC, 72-fold for M0 HER2- high risk breast cancer, 7-fold for M0 HER2+ high risk breast cancer, 270-fold for M1 HER2- high risk breast cancer, and 6-fold for M1 colorectal cancer based on clinical features that guide treatment decisions in real practice. Conclusions: Despite methodological attempts to reduce the influence of case mix on performance in EOM, the variability in cost of indication-specific treatments based on clinical characteristics not captured in the model might create performance risk for participating practices.

*Costs calculated based on 100% Medicare ASP. **Costs calculated for biosimilar trastuzumab-pkrb.