Toumazis I., Kurt M., Toumazi A., Karacosta L.G., Kwon C., "Comparative Effectiveness of Up-to-Three Lines of Chemotherapy Treatment Plans for Metastatic Colorectal Cancer", MDM Policy & Practice, In Press
Modern chemotherapy agents transformed standard care for metastatic colorectal cancer (mCRC) but raised concerns about the financial burden of the disease. We studied comparative effectiveness of treatment plans that involve up to three lines of therapies and impact of treatment sequencing on health and cost outcomes. We employed a Markov model to represent the dynamically changing health status of mCRC patients and used Monte-Carlo simulation to evaluate various treatment plans consistent with existing guidelines. We calibrated our model by a meta-analysis of published data from an extensive list of clinical trials and measured the effectiveness of each plan in terms of cost per quality-adjusted life-year (QALY). We examined the sensitivity of our model and results with respect to key parameters in two scenarios serving as base- and worst-cases for patients’ overall and progression free survivals. The derived efficient frontiers included 7 and 5 treatment plans in base- and worst-cases, respectively. The incremental cost-effectiveness ratio (ICER) ranged between $26,260 and $152,530 when the treatment plans on the efficient frontiers were compared against the least costly efficient plan in base-case, and between $21,256 to $60,040 in worst-case. All efficient plans were expected to lead to fewer than 2.5 AEs and on average successive AEs were spaced more than 9 weeks apart from each other in base-case. Based on ICER, all efficient treatment plans exhibit at least 87% chance of being efficient. Sensitivity analyses show that the ICERs were most dependent on drug acquisition cost, distributions of progression free and overall survivals, and health utilities. We conclude that improvements in health outcomes may come at high incremental costs and are highly dependent in the order treatments are administered.