ASSESSING THE ROLE OF SEQUENCING UP TO THREE LINES OF CHEMOTHERAPY IN METASTATIC COLORECTAL CANCER TREATMENT: A COST EFFECTIVENESS ANALYSIS

Purpose: Advancements in chemotherapy treatment have improved long term survival for metastatic colorectal cancer (mCRC) while raising financial concerns. We analyze the cost-effectiveness of clinically accepted combinations of up to three lines of therapies from 8 chemotherapy regimens to evaluate the progress made in colorectal cancer treatment and examine how treatment sequencing affects the effectiveness of treatment plans.

Methods: We considered the process of administering chemotherapy treatments for mCRC patients where treatments are discontinued when they lead to disease progression or 2 adverse events (AE). Upon an AE, treatment in use is paused for 2 weeks to clean the adverse effects from the event. We calibrated probability distributions for survival, disease progression, and the occurrence of AEs using published data from over 500 clinical trials and evaluated the effectiveness of treatment sequences with respect to quality-adjusted life-years (QALYs) and costs. All outcomes were discounted at a 3% annual rate. We analyzed the sensitivity of the incremental cost effectiveness ratios (ICERs) to costs and various parameters. We assessed the probabilistic efficiency behavior of the sequences, and calculated the number of AEs and occurrences of disease progressions under each of them through simulations.  

Results: We tested 178 different sequences including single and two-lines of chemotherapy regimens and 8 of them formed the efficient frontier. The mean cost/QALY ranged from $5,963 to $87,430 for the efficient sequences. Under none of the efficient treatment plans, the mean number of AEs was more than 2.5 and the events were spaced more than 30 weeks apart on average. The ICER of the treatment plan consisting of FOLFOX+Bevacizumab, FOLFIRI+Bevacizumab and CapeOx was $153,820/QALY over LV5FU alone, and it was most sensitive to treatment disutility, drug cost, and the AE likelihood. While all treatment plans were efficient with at least 50% chance, those on the frontier were more robust in that all of them were efficient with at least 87% chance with more than half of them being efficient with at least 97% chance.

Conclusions: Improvements in health outcomes may come at a high incremental cost for mCRC patients and be highly dependent on sequencing of treatments. While single and two lines of therapies can be efficient based on cost/QALY, majority of the efficient sequences consist of three-lines of therapies.