Value-Based Analysis of Therapies in Refractory Metastatic Colorectal Cancer in US

Background: Recent phase 2 trials have provided data supporting regorafenib dose optimization (ReDO) and trifluridine/tipiracil (TAS-102) with bevacizumab (TAS-BEV) as treatment options in refractory metastatic colorectal cancer (mCRC). Historically, regorafenib standard dose (RSD) and TAS-102 have been utilized as third-line options in mCRC. Given the incorporation of ReDO and TAS-BEV as treatment options, we sought to evaluate relative cost-effectiveness of ReDO vs. RSD, TAS-102, and TAS-BEV for mCRC from a payer perspective. Methods: A Markov model was constructed to estimate total costs and quality-adjusted life-years (QALYs) for ReDO, RSD, TAS-102, and TAS-BEV. Clinical parameters were obtained from phase 2 and 3 trials for comparators. Health state utility values were from the RSD phase 3 clinical trial. Incremental cost-effectiveness ratios (ICERs) were utilized to compare treatments. Model robustness was checked with one-way and probabilistic sensitivity analyses. Results: In the base case, ReDO was dominant over TAS-BEV (ie provided a higher QALY at a lower cost). ReDO produced an ICER of $104,308 per QALY relative to RSD and $37,966 relative to TAS-102. In one-way sensitivity analyses, monthly drug cost of TAS-BEV was the most influential parameter determining relative cost-effectiveness between TAS-BEV and ReDO. When TAS-102 and RSD were independently compared to ReDO, the most influential parameters were related to duration of OS and PFS and costs of managing AEs. Conclusions: The optimum dosing strategy for regorafenib has improved its benefit-to-toxicity ratio and relative cost-effectiveness compared to RSD, TAS-102, and TAS-BEV.