# Cost-effectiveness of switching to S-1 after fluoropyrimidine-induced hand-foot syndrome or cardiovascular toxicity in the treatment of metastatic colorectal cancer

## TL;DR

Switching to S-1 after hand-foot syndrome or cardiovascular toxicity in colorectal cancer treatment can be cost-effective.

## Contribution

This study evaluates the cost-effectiveness of switching to S-1 in metastatic colorectal cancer patients experiencing toxicity.

## Key findings

- Switching to S-1-based treatment after toxicity is cost-effective under certain scenarios.
- The incremental cost-effectiveness ratios for S-1 strategies were below or near the Dutch cost-effectiveness threshold.
- S-1 allows treatment continuation with lower toxicity compared to fluoropyrimidines.

## Abstract

The fluoropyrimidines 5-fluorouracil (5FU) and capecitabine are the backbone of systemic therapy for metastatic colorectal cancer (mCRC). Side effects include hand-foot syndrome (HFS) and cardiovascular toxicity (CVT), which may necessitate dose reductions or discontinuation of treatment. S-1 (Teysuno®) is an oral fluoropyrimidine that is licensed for use after fluoropyrimidine-induced HFS or CVT as it showed a lower incidence of those toxicities. It can be used as monotherapy or in combination with oxaliplatin or irinotecan. In this study, we assessed the cost-effectiveness of switching from 5FU or capecitabine-based treatment to S-1-based treatment after a patient with mCRC experiences HFS or CVT.

We developed a cohort-level decision analytic model to compare the costs and quality-adjusted life years (QALYs) when hypothetical patients would follow several different treatment strategies. We considered three different scenarios in which patients experienced toxicity on their initial first-line treatment of either CAPOX (1), FOLFOX (2) or capecitabine monotherapy (3), respectively. The step of first-line to second-line is denoted with an arrow (→). We used medication costs and administration costs, a lifelong time axis and compared strategies using incremental cost-effectiveness ratios (ICERs) and net benefit.

Costs for treatment administration often exceeded costs for treatment medication. For scenario 1, the ICER of the strategy of switching to SOX → Irinotecan (which was identical to SOX → IRIS) was €60 303 compared with the next best strategy of discontinuation of CAPOX → Irinotecan. This is below the threshold of €80 000/QALY used by the Dutch government for high-impact health conditions. Results of scenario 2 were similar to scenario 1. For scenario 3, the ICER of S-1 → SOX was €92 551 compared with reduced dosage capecitabine monotherapy → CAPOX.

S-1 based treatment strategies can be cost-effective when a treatment switch is required due to HFS or CVT during fluoropyrimidine-based treatment.

•S-1 is an oral fluoropyrimidine approved for use in mCRC patients who cannot continue treatment due to HFS or CVT.•S-1 showed lower incidences of HFS and CVT and allowed first-line treatment to immediately continue.•The cost-effectiveness of S-1 is not yet researched.•We developed a model to compare the costs and QALY for several different treatment strategies.•We found that S-1 based treatment strategies can be cost-effective when a switch is required due to HFS or CVT.

S-1 is an oral fluoropyrimidine approved for use in mCRC patients who cannot continue treatment due to HFS or CVT.

S-1 showed lower incidences of HFS and CVT and allowed first-line treatment to immediately continue.

The cost-effectiveness of S-1 is not yet researched.

We developed a model to compare the costs and QALY for several different treatment strategies.

We found that S-1 based treatment strategies can be cost-effective when a switch is required due to HFS or CVT.