China is the most affected country by gastric cancer as it accounts for 42.6% of the global gastric cancer incidence and 45% of all gastric cancer-related deaths . Gastric cancer has a heavy societal burden for China, so an economic assessment of therapy regimens is vital to keep the balance between clinical benefits and health care costs. Therefore, we established a cost-effective analysis from the Chinese societal perspective to investigate the cost-effectiveness of S-1 plus leucovorin and oxaliplatin versus S-1 plus cisplatin as first-line therapy in patients with advanced gastric cancer. In this study, oxaliplatin cohort costs more ($130,677.30 vs $129,149.99) and yields more health outcomes (0.64 QALYs vs 0.62 QALYs) than cisplatin cohort, resulting in the ICER of $61,331.63/QALY, which beyond the prespecified WTP threshold ($30,505/QALY), suggesting that S-1 plus leucovorin and oxaliplatin is not a cost-effective choice compared with S-1 plus cisplatin. Probabilistic sensitivity analysis suggested that this result was robust.
In terms of cost-effectiveness acceptability, as shown in Fig. 3, the acceptance rate varied as the WTP threshold changed. Oxaliplatin regimen was less likely to be accepted by patients until the WTP threshold was over $60,000/QALY. According to the WTP threshold we set before at $30,505/QALY, the oxaliplatin regimen is not cost-effective.
The most influential factors driving our model were RDI-adjusted costs of drug in PFS state in both cohorts and utility of PFS state, followed by societal costs in oxaliplatin cohort and costs of grade 3–4 AEs in both cohorts. The main differences of PFS state costs between the two cohorts were the price of oxaliplatin and cisplatin ($0.49 per mg vs $0.22 per mg), so decreasing the price of oxaliplatin could be a way to reduce ICER. Besides, the usage of S-1 was quite different (S-1 orally twice daily for 7 days every 2 weeks in oxaliplatin cohort vs S-1 orally twice daily for 21 days every 5 weeks in cisplatin cohort). Moreover, before and after treatment of the cisplatin group, hydration shall be performed to maintain sufficient urinary volume, and 5-HT3 receptor antagonist and steroid are recommended to be administered as pretreatment for nausea and vomiting. All the above were the reasons for the different costs in the PFS state between two cohorts.
Oxaliplatin cohort and cisplatin cohort both maintain a manageable toxicity profile. In terms of the grade 3–4 AEs, decreased appetite, diarrhea, peripheral sensory neuropathy, weight decrease, and hypoalbuminemia occurred more frequently in the oxaliplatin cohort, whereas neutropenia, anemia, and leukopenia were greater in the cisplatin cohort. Since the toxicity-related dose reduction may affect the results, we adjusted the drug costs according to RDI given by SOLAR. In the S-1 plus leucovorin and oxaliplatin group, 50% patients required S-1 and leucovorin dose reduction and oxaliplatin dose reduction was required in 48% patients. In the S-1 plus cisplatin group, 34% patients required S-1 dose reduction and cisplatin dose reduction was required in 28% patients. The AEs related costs were $175.32 and $235.94 per month in the oxaliplatin cohort and cisplatin cohort, respectively. The sensitivity analysis revealed that AEs related costs in both cohorts had an important impact on the ICER.
Many cost-effectiveness analyses have previously investigated chemotherapy regimens for gastric cancer. Some literature [16–17] has been published to compare S-1 and XELOX (capecitabine plus oxaliplatin) and concluded that XELOX was more cost-effective as adjuvant treatment, while capecitabine monotherapy was proved to be cost-effective compared with XELOX for elderly patients . ECX (epirubicin, cisplatin, and capecitabine) followed by FOLFIRI (fluorouracil, leucovorin, and irinotecan) has been demonstrated to be a preferred strategy . Another analysis  has been conducted to compare second-line treatment options for patients with advanced gastric cancer and revealed that irinotecan alone was the most cost-effective regimen. Moreover, recent evidence  suggested that compared with FOLFIRI, FOLFOX7 (oxaliplatin, 5-fluorouracil, and leucovorin) was a more cost-effective alternative as the first-line treatment. To our best knowledge, this study is the first economic evaluation to investigate the cost-effectiveness of S-1 plus leucovorin and oxaliplatin versus S-1 plus cisplatin as first-line therapy in patients with advanced gastric cancer.
There exist several limitations in this cost-effectiveness study. First and foremost, due to the SOLAR trial hadn’t collected quality of life-related information, the utility of disease pattern was extracted from a previously published advanced gastric cancer economic model, which may not accurately reflect the patients’ quality of life in the SOLAR trial. An updated health quality survey might improve accuracy and robustness. Moreover, detailed information about subsequent therapy was not given in the SOLAR trial, therefore, differences in the usage, dosage, and duration of paclitaxel, ramucirumab, and irinotecan in subsequent therapy could lead to calculation bias. Last but not least, costs could vary between different medical centers or different countries, and this may affect the generalizability of our research. In our sensitivity analysis, the costs of drugs in both cohorts had the most significant impact on the ICER. A future prospective cost-effectiveness study of S-1 plus leucovorin and oxaliplatin versus S-1 plus cisplatin in advanced gastric cancer is expected to further verify our results.
In conclusion, this study indicates that S-1 plus leucovorin and oxaliplatin is not a cost-effective choice compared with S-1 plus cisplatin as first-line therapy in patients with advanced gastric cancer from a Chinese society perspective, which could be considered in the decision-making process to make recommendations regarding the therapy for advanced gastric cancer patients.