Cost-effectiveness of Capecitabine + Irinotecan Versus Leucovorin + Fluorouracil + Irinotecan in the Second-line Treatment of Metastatic Colorectal Cancer in China

Highlights

• The present study is the first to investigate both the overall health and economic effects of capecitabine plus irinotecan versus leucovorin, fluorouracil, and irinotecan as second-line therapy for metastatic colorectal cancer based on the Phase III, randomized, double-blind AXEPT trial in China.

• In base-case analysis, our results suggested that mXELIRI treatment is a cost-effective second-line treatment for mCRC compared with FOLFIRI treatment in China.

• We performed sensitivity analysis to evaluate robustness of the model and address uncertainty of estimated parameters, and the results of the sensitivity analysis are consistent with the base case analysis.

• Our study should give suggestions of pharmacoeconomics for the decision-making process to make better recommendations regarding the second-line therapy for patients with metastatic colorectal cancer.

Abstract

Purpose

The AXEPT trial demonstrated that modified XELIRI (mXELIRI; capecitabine + irinotecan) was noninferior to standard treatment with FOLFIRI (fluorouracil + leucovorin + irinotecan), both ± bevacizumab, in the treatment of metastatic colorectal cancer (mCRC). The present study was designed to evaluate the cost-effectiveness of mXELIRI versus FOLFIRI as a second-line treatment of mCRC.

Methods

We developed a Markov model to estimate the costs and health outcomes of mXELIRI and FOLFIRI in patients with mCRC from the Chinese payer perspective. Survival data, transition probabilities, and health utility values were obtained from published studies. The costs of drugs were obtained from the West China Hospital. Life-years (LYs), quality-adjusted life-years (QALYs) gained, incremental cost-utility ratio (ICUR), and incremental cost-effectiveness ratio (ICER) values were regarded as the primary end points. One-way sensitivity analysis and probabilistic sensitivity analysis were performed to evaluate the impact of uncertainty of parameters in the analysis.

Findings

The effectiveness was found to be 0.48 QALYs (1.14 LYs) in the mXELIRI arm and 0.41 QALYs (1.05 LYs) in the FOLFIRI arm, with total costs of 29,896.41 US dollars (USD) in the mXELIRI arm and 28,894.68 USD in the FOLFIRI arm. The ICER and ICUR with mXELIRI versus FOLFIRI were 11,130.33 USD/LY and 14,310.43 USD/QALY gained, which were less than the willingness-to-pay threshold in China (25,840.88 USD/QALY).

Implications

Based on the results of this study, mXELIRI was found to be a cost-effective alternative to FOLFIRI as a second-line treatment of mCRC in patients in China.

Introduction

Colorectal cancer (CRC), involved in 881,000 deaths worldwide in 2018, is the third most commonly diagnosed cancer in men and the second most frequent in women.¹ Approximately 35% of patients with CRC are diagnosed with Stage IV metastatic disease when presenting with disease symptoms.² Moreover, 20%–50% of patients with Stage II/III disease progress to metastatic disease after curative surgery.^2,3

Fluorouracil (5-FU) + leucovorin + irinotecan (FOLFIRI) is the standard second-line treatment in patients with metastatic (m)-CRC.4, 5, 6 In 2000, Saltz et al⁷ demonstrated that, compared with patients receiving 5-FU + leucovorin, patients treated with FOLFIRI displayed a mean 36% lower risk for progression and a 22% lower risk for death. Capecitabine is an oral fluoropyrimidine that is activated in tumor tissues by a 3-step enzymatic conversion culminating in the formation of thymidine phosphorylase.⁸ Capecitabine, unlike many other antitumor drugs, does not require IV administration. Thus, the additional cost of a peripherally inserted central catheter and possible adverse events (AEs) that occur with IV administration (eg, phlebitis) do not apply to patients receiving capecitabine treatment. The results of a Phase 3 multicenter, open-label, randomized, noninferiority trial (AXEPT [Modified XELIRI (Capecitabine Plus Irinotecan) Versus FOLFIRI (Leucovorin, 5-FU, and Irinotecan), Both Either With or Without Bevacizumab, as Second-Line Therapy for Metastatic Colorectal Cancer]⁹; ClinicalTrials.gov identifier: NCT01996306) suggested that modified XELIRI (mXELIRI; capecitabine + irinotecan) ± bevacizumab is well tolerated and noninferior to FOLFIRI ± bevacizumab in the second-line treatment of mCRC.

Decision makers and patients require more information in addition to therapeutic efficacy to make reasonable decisions regarding cancer treatment, and cost represents a crucial factor. In recent years, expenditures in cancer care have proliferated, with cancer having become one of the most common concerns worldwide, especially in countries, such as China, with limited health care resources. Thus, the evaluation of the pharmacoeconomic profile of treatment regimens is increasingly crucial. Cost-effectiveness analysis is a principal tool in health economic evaluation that allows for the analysis of both the cost of a specific medical intervention and the benefits that it provides.¹⁰ Several studies have evaluated the cost-effectiveness of capecitabine + 5-FU in patients with mCRC in a variety of countries. Shiroiwa et al,¹¹ Tran et al,¹² and Wen et al¹³ reported that, compared with oxaliplatin + IV 5-FU/leucovorin, capecitabine + oxaliplatin is a cost-effective regimen in patients with mCRC in Japan, Australia, and China, respectively. The findings from a study by De Portu et al¹⁴ suggested that capecitabine treatment cost less than 5-FU treatment. However, no economic evaluation has compared the differences in costs and outcomes between the mXELIRI and FOLFIRI treatment regimens. Therefore, the present study was performed to investigate the cost-effectiveness of mXELIRI versus FOLFIRI in the second-line treatment of mCRC from the Chinese payer perspective.