First-line serplulimab plus chemotherapy versus chemotherapy in PD-L1-positive esophageal squamous-cell carcinoma: a cost-effectiveness analysis.

Patients with PD-L1-positive esophageal squamous-cell carcinoma (ESCC) were significantly more likely to survive when treated with serplulimab plus cisplatin plus 5-fluorouracil (serplulimab-CF). At this point, it is unknown whether this expensive therapy is cost-effective. From the Chinese healthcare system's perspective, we aimed to evaluate serplulimab-CF versus CF alone for cost-effectiveness. A partitioned survival model was constructed based on the ASTRUM-007 trial. Quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio (ICER) were calculated. A further analysis of subgroups and scenarios was conducted. The willingness to pay (WTP) threshold of $38,258/QALY or $84,866/QALY is defined as three times the per capita gross domestic product value of the general region or affluent region. Compared with CF alone, in the overall (scenario 1), patients with PD-L1 expression level of 1 ≤ CPS < 10 (scenario 2), and patients with PD-L1 CPS ≥ 10 (scenario 3) populations, the ICERs were $69,025/QALY, $82,533/QALY, and $75,436/QALY for serplulimab-CF. Nevertheless, the probability of serplulimab-CF becoming cost-effective based on scenarios 1, 2, and 3 is only 2.71%, 0.94%, and 2.84%, respectively, at a WTP threshold of $38,258/QALY. When serplulimab costs < $4.84/mg, serplulimab-CF may be cost-effective at the WTP threshold of $38,258/QALY; otherwise, CF was preferred. Similar results were obtained from sensitivity analyses, suggesting the robustness of these findings. There was no cost-effectiveness in general regions of China for serplulimab-CF in PD-L1-positive ESCC compared to CF, although it is probably considered cost-effective in affluent regions. Serplulimab-CF may achieve favorable cost-effectiveness by lowering the price of serplulimab.

Immune checkpoint inhibitors as the second-line treatment for advanced esophageal squamous cell carcinoma: a cost-effectiveness analysis based on network meta-analysis.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have demonstrated superior clinical efficacy in prolonging overall survival (OS) as the second-line treatment for advanced or metastatic esophageal squamous cell carcinoma (ESCC), and were recommended by the guidelines. However, it remains uncertain which ICI is the most cost-effective. This study assessed the cost-effectiveness of ICIs as the second-line treatment for ESCC based on the perspective of the Chinese healthcare system. METHODS: A network meta-analysis (NMA) was performed to obtain the Hazard ratios (HRs) for indirect comparisons. A three-state Markov model with a 10-year time horizon was conducted to assess the cost-effectiveness. The state transition probabilities were calculated with Kaplan-Meier (KM) curves data from clinical trial and HRs from the NMA. Utilities and costs were derived from local charges or previously published studies. Univariate and probabilistic sensitivity analyses (PSA) were performed to examine model robustness. The results were assessed based on the total costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). RESULTS: Five clinical trials (ATTRACTION-3, ESCORT, KEYNOTE-181, ORIENT-2, RATIONALE-302) with a total of 1797 patients were included in the NMA. The NMA showed that both camrelizumab and tislelizumab received relatively high rankings for progression-free survival (PFS) and OS. Compared with sintilimab, treatment with tislelizumab and camrelizumab gained 0.018 and 0.034 additional QALYs, resulting in incremental ICERs of $75,472.65/QALY and $175,681.9/QALY, respectively. Nivolumab and pembrolizumab produced lower QALYs and greater costs, suggesting that both were dominated in comparison to sintilimab. HRs and health state utilities were the most influential parameters in most univariate sensitivity analyses of paired comparisons. PSA results suggested that sintilimab had an 84.4% chance of being the most cost-effective treatment regimen at the WTP threshold of $38,223.34/QALY. In the scenario analysis, sintilimab would no longer be cost-effective, if the price of camrelizumab was assumed to decrease by 64.6% or the price of tislelizumab was assumed to decrease by 16.9%. CONCLUSIONS AND RELEVANCE: Among the five potential competing ICIs, sintilimab was likely to be the most cost-effective regimen as the second-line treatment for locally advanced or metastatic ESCC in China.

Cost-effectiveness analysis of tislelizumab vs. camrelizumab for the treatment of second-line locally advanced or metastatic esophageal squamous cell carcinoma.

BACKGROUND: Esophageal carcinoma is a type of cancer that occurs in the esophagus. For patients with locally advanced or metastatic esophageal squamous cell carcinoma who have either experienced disease progression following first-line standard chemotherapy or are intolerant to it, the prognosis is typically poor. Additionally, these patients often bear a substantial economic burden during the course of their treatment. Tislelizumab is a selective PD-1 inhibitor with efficacy proven in locally advanced or metastatic esophageal squamous cell carcinoma. The study aims to evaluate the cost-effectiveness of tislelizumab versus camrelizumab as the second-line treatment in locally advanced or metastatic esophageal squamous cell carcinoma (ESCC) patients in China. METHODS: From the perspective of China's healthcare system, the partitioned survival model with three health states was established in a 3-week cycle and a lifetime horizon. Anchored matching adjusted indirect comparison was used for survival analyses based on individual patient data from RATIONALE 302 trial and the published ESCORT study due to the lack of head-to-head clinical trials. Only direct medical costs were included. Costs and utility values were derived from local charges, the published literature, and related databases. Sensitivity analyses and a scenario analysis were also performed to verify the robustness of the model results. RESULTS: Compared with camrelizumab monotherapy, tislelizumab monotherapy incurred a lower lifetime cost ($8,346 vs. $8,851) and yielded higher quality-adjusted life-years (QALYs) (0.87 vs. 0.63), which resulted in an incremental cost-effectiveness ratio (ICER) of -$2,051/QALY. Tislelizumab monotherapy is a dominant option over camrelizumab monotherapy in China. The three primary parameters upon which this result was most sensitive were the unit cost of camrelizumab, the unit cost of tislelizumab, and the duration of reactive cutaneous capillary endothelial proliferation (RCCEP). According to the probabilistic sensitivity analysis (PSA), tislelizumab monotherapy was 100% cost-effective when the WTP was 1-3 times GDP per capita in China($11,207/QALY∼$33,621/QALY). Scenario analysis showed that the result was consistent. CONCLUSION: Tislelizumab monotherapy is a dominant option compared with camrelizumab monotherapy as the second-line treatment for locally advanced or metastatic ESCC in China.

Cost-effectiveness analysis of tislelizumab plus chemotherapy as the first-line treatment for advanced or metastatic oesophageal squamous cell carcinoma in China.

OBJECTIVE: We aimed to investigate the cost-effectiveness of tislelizumab plus chemotherapy compared to chemotherapy alone as a first-line treatment for advanced or metastatic oesophageal squamous cell carcinoma (OSCC). METHODS: A partitioned survival model was developed to evaluate the cost-effectiveness of tislelizumab plus chemotherapy versus chemotherapy alone in patients with advanced or metastatic OSCC over a 10-year lifetime horizon from the perspective of the Chinese healthcare system. Costs and utilities were derived from the drug procurement platform and published literature. The model outcomes comprised of costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER). One-way and probabilistic sensitivity analyses were conducted to address uncertainty and ensure the robustness of the model. RESULTS: Tislelizumab plus chemotherapy yielded an additional 0.337 QALYs and incremental costs of $7,117.007 compared with placebo plus chemotherapy, generating an ICER of $21,116.75 per QALY, which was between 1 time ($12,674.89/QALY) and 3 times GDP ($38,024.67/QALY) per capita. In one-way sensitivity analysis, the ICER is most affected by the cost of oxaliplatin, paclitaxel and tislelizumab. In the probabilistic sensitivity analysis, when the willingness-to-pay threshold was set as 1 or 3 times GDP per capita, the probability of tislelizumab plus chemotherapy being cost-effective was 1% and 100%, respectively. CONCLUSION: Tislelizumab plus chemotherapy was probably cost-effective compared with chemotherapy alone as the first-line treatment for advanced or metastatic OSCC in China.

Cost-effectiveness analysis of PD-1 inhibitors as second-line therapy for advanced or metastatic esophageal squamous cell carcinoma in China: an economic evaluation based on network meta-analysis.

BACKGROUND: Several economic studies have assessed the cost-effectiveness of programmed cell death protein-1 (PD-1) inhibitors compared to second-line chemotherapy in treating esophageal squamous cell carcinoma (ESCC). However, there is a lack of economic comparisons among the different PD-1 inhibitors. AIM: This study aimed to assess the cost-effectiveness of PD-1 inhibitors (nivolumab, pembrolizumab, camrelizumab, and tislelizumab) in second-line treatment for advanced or metastatic ESCC within the Chinese healthcare system. METHOD: The clinical trials were systematically retrieved from PubMed, Embase, Web of Science, and the Cochrane Library. We established a fractional polynomials model to conduct a network meta-analysis, enabling the calculation of hazard ratios and expected survival rates. Economic outcomes were estimated using a partitioned survival model. The costs and utilities were gathered from published sources. The threshold for willingness-to-pay (WTP) for a quality-adjusted life year (QALY) was set at three times China's per capita gross domestic product in 2022. Sensitivity analyses (SA) were performed to address uncertainties in the model. RESULTS: Four phase III randomized controlled trials were included, evaluating the cost-effectiveness of four PD-1 inhibitors, camrelizumab, nivolumab, tislelizumab, and pembrolizumab, compared to chemotherapy for the second-line treatment of advanced or metastatic ESCC. For camrelizumab, nivolumab, tislelizumab, and pembrolizumab, the corresponding incremental cost-effectiveness ratios were $27,375.43/QALY, $205,312.19/QALY, $9,266.73/QALY, and $220,368.10/QALY, respectively. The SA results indicated the robustness of the base analysis findings. CONCLUSION: From the Chinese healthcare system, under the WTP of $38,253.48/QALY, tislelizumab is a cost-effective treatment option for the second-line treatment of advanced or metastatic ESCC.

Cost-effectiveness analysis of toripalimab plus chemotherapy for patients with advanced esophageal squamous cell carcinoma in China.

BACKGROUND: The aim of the current analysis was to evaluate the cost-effectiveness of toripalimab plus chemotherapy compared with chemotherapy alone as the first-line option for patients with advanced esophageal squamous cell carcinoma (ESCC) from the perspective of Chinese health-care system. METHODS: A partitioned survival model was conducted to track 3-week patients' transition and evaluate the health and economic outcomes in 10-year horizon of the two competing first-line treatment among toripalimab plus chemotherapy and chemotherapy alone. The survival data were gathered from the JUPITER-06 trial, and cost and utility values were obtained from the local charges and published studies. Total costs, life-years, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER) were the model outcomes. Sensitivity and subgroup analyses were conducted. RESULTS: Treatment with toripalimab plus chemotherapy yields marginal cost of $8,639.74 and additional 0.65 QALYs, resulting in an ICER of $13,280.97 per additional QALY gained, which was lower than the willingness-to-pay (WTP) threshold of $38,224 in China. Sensitivity and subgroup analyses confirmed the robustness of the model outcomes. CONCLUSIONS: Toripalimab plus chemotherapy was likely to be the cost-effective first-line option for patients with advanced ESCC compared with chemotherapy alone with the WTP threshold of $38,224 per additional QALY gained from the perspective of the Chinese health-care system.

First-Line Tislelizumab for Advanced or Metastatic Esophageal Squamous Cell Carcinoma:A Cost-Effectiveness Analysis.

OBJECTIVE: The primary objective of this current study is to evaluate the cost-effectiveness of incorporating tislelizumab into the first-line treatment of metastatic or advanced esophageal squamous cell carcinoma (ESCC) in comparison to placebo with chemotherapy. METHOD: We conducted a partitioned survival model with a time horizon of 10 years from a Chinese perspective. The direct medical costs were collected from the local setting in China. To enhance the credibility and robustness of the findings, sensitivity analyses were also conducted. RESULTS: The inclusion of tislelizumab in conjunction with chemotherapy was shown to significantly enhance quality-adjusted life years (QALY) by 0.328 when compared to chemotherapy alone. This improvement comes at an additional cost of $9833.694. The incorporation of tislelizumab into the treatment regimen for advanced ESCC results in an incremental cost-effectiveness ratio (ICER) of $29980.774/QALY gained, which falls below the WTP threshold of $37304.346/QALY in China. One-way sensitivity analyses showed that no parameters were found to be adjustable within a specific range without altering the overall outcomes of our study. CONCLUSION: Tislelizumab plus chemotherapy as first-line treatment for advanced or metastatic ESCC is may be a cost-effective option compared to chemotherapy alone.

Economic evaluation of serplulimab plus chemotherapy as the first-line treatment of oesophageal squamous cell carcinoma in China.

OBJECTIVE: The ASTRUM-007 study confirmed the significant efficacy and safety of serplulimab plus chemotherapy for patients with locally advanced/metastatic, programmed cell death-ligand 1 positive oesophageal squamous cell carcinoma (OSCC). The economics of this regimen, however, is unclear. Therefore, this study aimed to evaluate the cost-effectiveness of adding serplulimab to chemotherapy for the treatment of advanced OSCC from the perspective of the Chinese healthcare system. DESIGN: A partitioned survival model was established to simulate the costs and outcomes of chemotherapy versus serplulimab plus chemotherapy. The survival data came from the ASTRUM-007 study. Only direct medical costs were considered, and utility values were referred to the literature. Sensitivity analysis was performed to assess the effect of parameter uncertainty on the model. OUTCOME MEASURES: Total costs, incremental costs, life years, quality-adjusted life years (QALYs), incremental QALYs and incremental cost-effectiveness ratio (ICER). RESULTS: The base case analysis showed that the cost of serplulimab plus chemotherapy (US$69 356) was US$41 607 higher than that of chemotherapy (US$27 749), but it also gained 0.38 QALYs more (1.38 vs 1 QALYs), with an ICER of US$110 744.36/QALY, which was higher than the willingness to pay. The factors that most influenced the ICER were the price of serplulimab, weight and utility value of the progression-free survival stage. The subgroup analysis and scenario analysis also demonstrated that serplulimab plus chemotherapy was not economical. CONCLUSIONS: Compared with chemotherapy, serplulimab coupled with chemotherapy was not cost-effective for the treatment of advanced OSCC in China.

Tislelizumab Plus Chemotherapy Versus Placebo Plus Chemotherapy as First-Line Treatment for Chinese Patients with Advanced Esophageal Squamous Cell Carcinoma: A Cost-Effectiveness Analysis.

BACKGROUND AND OBJECTIVES: Advanced esophageal squamous cell carcinoma (ESCC) is a prevalent and highly malignant tumor with a poor prognosis. Recently, the RATIONALE-306 trial demonstrated that tislelizumab combined with chemotherapy provided overall survival benefits for these patients. This study aimed to assess the cost-effectiveness of this treatment approach in Chinese patients with advanced ESCC from the perspective of healthcare system. METHODS: A Markov model was constructed to assess the economic and health benefits associated with tislelizumab plus chemotherapy over a 10-year lifetime horizon, utilizing data from the RATIONALE-306 trial. The analysis encompassed the calculation of several key parameters, including the incremental cost-effectiveness ratio (ICER), total cost, incremental cost, total effectiveness, and incremental effectiveness. Tislelizumab was considered cost-effective if the ICER obtained was below the willingness-to-pay (WTP) threshold of US$38,223 per quality-adjusted life-year (QALY); otherwise, it would be deemed not cost-effective. To ensure the robustness of the findings, the results were subjected to one-way sensitivity analysis and probabilistic sensitivity analysis (PSA). RESULTS: In the base-case analysis, the incremental effectiveness and cost associated with tislelizumab plus chemotherapy, compared to chemotherapy alone, were determined to be 0.40 QALY and US$7604, respectively. This resulted in an ICER of US$18,846 per QALY, which is below the WTP threshold of US$38,223 per QALY. Furthermore, the results from the one-way sensitivity analysis and PSA indicated robustness of the findings. CONCLUSION: Our lifetime simulation study demonstrated that, in the case of advanced ESCC, the combination of tislelizumab and chemotherapy offers increased effectiveness compared to chemotherapy alone, albeit at a higher cost. Moreover, considering the current WTP threshold in China, the addition of tislelizumab to chemotherapy is considered a cost-effective approach.

Cost-effectiveness analysis of serplulimab as first-line treatment for advanced esophageal squamous cell carcinoma.

Objective: To evaluate the cost-effectiveness of serplulimab as first-line treatment for patients with advanced esophageal squamous cell carcinoma from the perspective of the Chinese healthcare system. Materials & methods: A partitioned survival model was created to evaluate costs and health outcomes. The model's robustness was evaluated using one-way and probabilistic sensitivity analyses. Results: Serplulimab demonstrated an incremental cost-effectiveness ratio of $104,537.375/quality-adjusted life-year in the overall population group. Subgroup analysis showed that serplulimab had incremental cost-effectiveness ratios of $261,750.496/quality-adjusted life-year and $68,107.997/quality-adjusted life-year in the populations with PD-L1 1 ≤ combined positive score <10 and PD-L1 combined positive score ≥10, respectively. Conclusion: Incremental cost-effectiveness ratios of serplulimab therapy were found to exceed the willingness-to-pay threshold of $37,304.34. Thus, serplulimab is not cost-effective compared with chemotherapy as a first-line treatment for esophageal squamous cell carcinoma patients.

Cost-effectiveness analysis of serplulimab plus chemotherapy in the first-line treatment for PD-L1-positive esophageal squamous cell carcinoma in China.

Objective: The ASTRUM-007 trial (NCT03958890) demonstrated that serplulimab plus chemotherapy administered every 2-week significantly improved progression-free and overall survival in patients with previously untreated, programmed death-ligand 1 (PD-L1) positive advanced esophageal squamous-cell carcinoma (ESCC). This study was aimed to investigate the cost-effectiveness of serplulimab plus chemotherapy in the first-line treatment of PD-L1-positive advanced ESCC. Methods: A partitioned survival model with a 2-week cycle and a 10-year time horizon was constructed from the Chinese healthcare system perspective. The survival data, direct medical costs and utilities were derived from the ASTRUM-007 trial, YAOZHI database and published sources. Total costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs) were calculated. Scenario, one-way and probabilistic sensitivity analyses were performed to assess the uncertainty around model parameters. Results: Compared with chemotherapy, serplulimab plus chemotherapy provided additional 0.27 QALYs with an incremental cost of $33,460.86, which had an ICER of $124,483.07 per QALY. The subgroup analyses revealed that the ICERs of serplulimab plus chemotherapy were $134,637.42 and $105,589.71 in advanced ESCC patients with 1 ≤ CPS < 10 and CPS ≥ 10, respectively. The price of serplulimab, patient weight, utility values and discount rate were the most influential parameters on base-case results. At a willingness-to-pay threshold of three times per capita GDP ($40,587.59) in 2022, the probability of serplulimab plus chemotherapy being cost-effective was 0% compared with chemotherapy. When the price of serplulimab decreased by 70%, the probabilities of serplulimab plus chemotherapy being cost-effective were 81.42%, 67.74% and 96.75% in advanced ESCC patients with PD-L1-positive, PD-L1 1≤CPS<10 and CPS≥10, respectively. Conclusion: Serplulimab plus chemotherapy in the first-line treatment for PD-L1-positive advanced ESCC might not be cost-effective in China.

Cost-effectiveness of camrelizumab plus chemotherapy versus chemotherapy alone as first-line therapy in advanced or metastatic esophageal squamous cell carcinoma.

OBJECTIVE: Camrelizumab combination therapy for advanced or metastatic esophageal squamous cell carcinoma (ESCC) has considerable survival benefits. This study investigated the cost-effectiveness of camrelizumab combination therapy versus chemotherapy alone as a first-line treatment for patients with ESCC from the perspective of the Chinese healthcare system. METHODS: A three-state partitioned survival model was developed to estimate total costs, life years (LYs), quality-adjusted life years (QALYs), incremental cost-effectiveness ratios (ICERs) and incremental net health benefits (INHBs) over a 20-year time horizon. Sensitivity and scenario analyses were also performed. RESULTS: Camrelizumab plus chemotherapy increased QALYs by 0.30 (0.43 LYs), with an incremental cost of $9,272. The ICERs for camrelizumab plus chemotherapy vs chemotherapy alone was $31,062/QALY ($21,599/LY), and the INHB was 0.05 QALY at the cost-effective threshold of $37,653/QALY (3 times China's GDP per capita). One-way sensitivity analyses showed that the ICER was the most sensitive to utility values in the PFS state. Probabilistic sensitivity analyses suggested that camrelizumab combination therapy had a probability of 74.04% cost-effectiveness at a threshold of $37,653/QALY. Scenario analyses confirmed that the findings were robust. CONCLUSIONS: Camrelizumab combination therapy is likely to have a cost-effectiveness advantage over chemotherapy alone for previously untreated advanced or metastatic ESCC in China.

Economic evaluation of toripalimab plus chemotherapy compared with chemotherapy as first-line treatment for advanced esophageal squamous cell carcinoma in China.

OBJECTIVES: The purpose of this study was to compare the cost-effectiveness of toripalimab versus Chemotherapy for patients with advanced esophageal squamous cell carcinoma (ESCC) from the perspective of the Chinese healthcare system. METHODS: A partitioned survival model was designed. Clinical data on survival was taken from the JUPITER-06 trials. Direct medical expenditures and utilities were gathered from published literature and a local database. One-way and probability sensitivity methods were used to evaluate the model's robustness. RESULTS: Compared with chemotherapy alone, toripalimab offered an incremental cost of $8950.427 with an additional 0.294 QALYs, yielding an ICER of 30,443.629$/QALYs first-line therapy for advanced ESCC. The ICER was below the threshold of willingness to pay in China, indicating that the toripalimab group had a cost-effective advantage. Sensitivity analysis showed that the ICERs were most sensitive to the utility of PD, but all the parameters had no significant impact on the model's outcomes. CONCLUSION: Toripalimab may be a cost-effective first-line treatment choice in our research when compared to chemotherapy alone for patients with advanced ESCC.

Cost-effectiveness of sintilimab plus chemotherapy versus chemotherapy alone as first-line treatment of locally advanced or metastatic oesophageal squamous cell carcinoma.

Background: Sintilimab plus chemotherapy significantly prolongs overall survival (OS) for patients with advanced or metastatic oesophageal squamous cell carcinoma (OSCC). However, the cost-effectiveness of this high-priced therapy is currently unknown. We evaluated the cost-effectiveness of sintilimab plus chemotherapy vs chemotherapy alone as fist-line therapy in patients with advanced or metastatic OSCC from the perspective of Chinese healthcare system. Methods: A partitioned survival model consisting of 3 discrete health states was constructed to assess the cost and effectiveness of sintilimab plus chemotherapy vs chemotherapy as first-line treatment of OSCC. Key clinical data in the model came from the ORIENT-15 trial. Costs and utilities were collected from published sources. Life-years, quality-adjusted life-years (QALYs), incremental cost-effectiveness ratio (ICER), incremental net health benefits (INHB), and incremental net monetary benefits (INMB) were calculated for the two treatment strategies. One-way and probabilistic sensitivity analyses were conducted to account for uncertainty and model stability. Additional subgroup and scenario analyses were performed. Results: Treatment with sintilimab plus chemotherapy provided an additional 0.37 QALYs and an incremental cost of $8,046.58 compared with chemotherapy, which resulted in an ICER of $21,782.24 per QALY gained. One-way sensitivity analysis revealed that the model was most sensitive to utility of progression-free survival (PFS) and the cost of sintilimab. The probabilistic sensitivity analysis indicated that the probability of sintilimab plus chemotherapy being cost-effective was 0.01%, 76.80% and 98.60% at the threshold of 1, 2 or 3 times GDP per capita per QALY, respectively. Subgroup analysis found that all subgroups other than PD-L1 expression combined positive scores < 1 subgroup favored sintilimab plus chemotherapy treatment due to its association with positive INHBs by varying the hazard ratios for OS and PFS. The scenario analyses showed altering the time horizon of the model or fitting survival curves separately did not reverse results of the model. Conclusion: Sintilimab plus chemotherapy was associated with improved QALYs and an additional cost but was estimated to be cost-effective compared with chemotherapy alone as a first-line treatment for patients with advanced or metastatic OSCC at the commonly adopted willingness-to-pay threshold of 3 times GDP per capita per QALY in China.

Cost-effectiveness of toripalimab plus chemotherapy for advanced esophageal squamous cell carcinoma.

BACKGROUND: Toripalimab is an immune checkpoint inhibitor (ICI) against programmed death ligand 1 (PD-L1). It has been approved for advanced esophageal squamous cell carcinoma (ESCC) as the first-line treatment due to significantly improved progression-free survival (PFS) and overall survival (OS) in the JUPITER-06 trial. AIM: This study aimed to compare the cost-effectiveness between toripalimab plus chemotherapy and placebo plus chemotherapy from the perspective of the Chinese health system. METHOD: The study developed a 3-year partitioned survival model to assess costs and outcomes in two treatment groups with or without toripalimab. The critical indicator was the incremental cost-effectiveness ratio (ICER). Scenario and sensitivity analyses were performed to evaluate the robustness of the findings and identify the parameters with the greatest impact on cost-effectiveness. RESULTS: In the base case analysis, the incremental effectiveness and cost of toripalimab plus chemotherapy versus placebo plus chemotherapy were 0.26 quality-adjusted life year (QALYs) and $11,254.84, respectively, resulting in an ICER of $43,405.09/QALY, higher than the 2021 willingness-to-pay threshold in China ($37,658.70/QALY). The results were sensitive to the utility of PFS, the incidence of neutropenia in the toripalimab group, and the cost of toripalimab. The toripalimab plus chemotherapy group was cost-effective only if the price of toripalimab decreased by more than 40%. CONCLUSION: Adding toripalimab to chemotherapy was not cost-effective in patients with advanced ESCC in China.

Cost-Effectiveness Analysis of Toripalimab Plus Paclitaxel and Cisplatin as First-Line Treatment for Advanced or Metastatic Esophageal Squamous Cell Carcinoma.

INTRODUCTION: First-line treatment with toripalimab plus paclitaxel and cisplatin (TTP) is very effective for patients with advanced or metastatic esophageal squamous cell carcinoma (ESCC) in China, although its effects on economic burden are unknown. The present study aimed to evaluate the cost-effectiveness of TTP from the perspective of the Chinese healthcare system. METHODS: A Markov model was established to evaluate the cost-effectiveness of first-line treatment with TTP for patients with advanced or metastatic ESCC. Survival data were derived from the JUPITER-06 trial. The costs and utilities were gathered from the literature and a local database. The primary outcomes were total costs, quality-adjusted life year (QALY), and incremental cost-effectiveness ratios (ICERs) at a willingness-to-pay (WTP). One-way and probability sensitivity analyses were used to evaluate the robustness of the model. RESULTS: The total cost of TTP was $123,646.43 and gained 1.10 QALYs, while the paclitaxel and cisplatin (TP) chemotherapy group yielded 0.84 QALY at cost of $16,259.65. First-line TTP treatment yielded an incremental cost of $7,386.78 with an additional 0.26 QALY, providing an ICER of $28,348.42/QALY, which was lower than the WTP threshold ($36,257.91) in China. CONCLUSIONS: TTP was likely more cost-effective than TP chemotherapy from the perspective of the Chinese healthcare system. This study may provide evidence required to establish decision-making criteria to support guidance for cost-effective selection of an immunotherapeutic regimen.

Cost-effectiveness analysis of pembrolizumab vs. chemotherapy as second-line treatment for advanced esophageal carcinoma in the United States.

Background: The national Comprehensive Cancer Network has suggested pembrolizumab as a second-line therapy for esophageal squamous cell carcinoma (ESCC) patients with a programmed death ligand-1 (PD-L1) combined positive score (CPS) ≥ 10. However, despite the increased survival rate associated with pembrolizumab in these patient population, the high cost of pembrolizumab may influence its antitumor effect. This study aimed to evaluate the cost-effectiveness of pembrolizumab compared to chemotherapy as second-line treatments for esophageal carcinoma (EC) based on KEYNOTE-181 trial. Methods: A Markov model was constructed using TreeAge 2021 based on three different groups: all intent-to-treat patients (ITT population), patients with ESCC (ESCC population), and patients with a PD-L1 CPS ≥10 (CPS ≥10 population). Incremental cost, Incremental effect, Life-years, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio (ICER) were calculated. Analyses were conducted on the setting of a willingness-to-pay threshold of $150,000 from the US perspective. Results: The ICERs for pembrolizumab were $157,589.545 per QALY, $60,238.823 per QALY, and $100,114.929 per QALY compared with chemotherapy in the ITT, ESCC, and CPS≥10 populations, respectively. The ICER of the ITT population was higher than $150,000, suggesting that pembrolizumab was not a cost-effective treatment scheme in patients with a PD-L1 CPS ≤ 10 or esophageal adenocarcinoma. The ICER was < $150,000 in the ESCC and CPS≥10 populations, indicating that pembrolizumab was cost-effective in these two subgroups. Conclusion: The determining of pembrolizumab as a cost-effective second-line therapy for EC in the United States depends on the histologic type and PD-L1 expression.

Assessment of durable chemoimmunotherapy response via circulating tumor DNA in advanced esophageal squamous cell carcinoma.

Immune checkpoint inhibitor (ICI)-based therapies have shown promising advances for the first-line treatment of advanced or metastatic esophageal cancer (EC). However, few studies concerning the identification of patients who achieve durable response from ICIs have been previously reported. In the present study, pre- and on-treatment plasma circulating tumor DNA (ctDNA) were analyzed in 10 patients with advanced esophageal squamous cell cancer (ESCC) receiving first-line chemoimmunotherapy. Patients with decreased molecular tumor burden index (mTBI) >7% experienced longer progression-free survival (PFS) and durable clinical benefit (DCB, PFS ≥ 6 months). In addition, five patients showed stable disease at first scan, all three patients with decreased mTBI > 7% achieved DCB, while two cases with decreased mTBI ≤ 7% experienced non-DCB. Our results demonstrate that ctDNA monitor might help identify which ESCC patients respond to chemoimmunotherapy.

Cost-Effectiveness Analysis of Pembrolizumab Plus Chemotherapy vs. Chemotherapy Alone as First-Line Treatment in Patients With Esophageal Squamous Cell Carcinoma and PD-L1 CPS of 10 or More.

Background: This study aimed to analyze the economics of pembrolizumab plus chemotherapy as first-line treatment in patients with esophageal squamous cell carcinoma (ESCC) and programmed cell death-Ligand 1 (PD-L1) combined positive score (CPS) of 10 or more in China. Methods: Based on the advanced ESCC of the KEYNOTE-590 clinical trial data, a Markov model was performed to simulate the clinical course and evaluate the patient's total lifetime, total costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER) for pembrolizumab plus chemotherapy (cisplatin and 5-fluorouracil) vs. chemotherapy alone in first-line treatment of ESCC and PD-L1 CPS of 10 or more. Utility values and direct costs related to the treatments were gathered from the published literature data. One-way and probabilistic sensitivity analyses were conducted to check the stability of the model. Results: The baseline analysis indicated that the incremental effectiveness and cost of pembrolizumab plus chemotherapy vs. chemotherapy alone added 1.23 QALYs and resulted in an incremental cost of $51,320.22, which had an ICER of $41,805.12/QALY, higher than the willingness-to-pay (WTP) threshold of China ($37,663.26/QALY). The sensitivity analysis demonstrated that the ICERs were most sensitive to the cycle of pembrolizumab used and the cost of pembrolizumab. Conclusion: The result of our present analysis suggests that the addition of pembrolizumab plus chemotherapy as first-line treatment might not be cost-effective for patients with ESCC and PD-L1 CPS of 10 or more in China.

Cost-Effectiveness of Nivolumab Immunotherapy vs. Paclitaxel or Docetaxel Chemotherapy as Second-Line Therapy in Advanced Esophageal Squamous Cell Carcinoma in China.

This study aimed to evaluate and compare nivolumab's cost-effectiveness with chemotherapy in patients with advanced esophageal squamous cell carcinoma from the Chinese healthcare system perspective. To this end, the researchers utilized a partitioned survival model with three mutually exclusive health stages. The characteristics of the patients used as inclusion and exclusion criteria in this model were the same as those used for patients with advanced esophageal squamous cell carcinoma in the ATTRACTION-3 study. The ATTRACTION-3 trial, which took place between January 7, 2016 and November 12, 2018, also yielded important clinical data. Data on medical and economic preferences were collected from real-world clinical practices. Costs, quality-adjusted life years, and incremental cost-effectiveness ratio were calculated for the two therapy options. The model uncertainty was investigated using a deterministic and probabilistic sensitivity analysis. When compared to chemotherapy, nivolumab was linked with an increase of 0.28 quality-adjusted life years with an increased cost of US$ 36,956.81 per patient in the base case analysis of a hypothetical sample of 419 patients. The incremental cost-effectiveness ratio in the deterministic sensitivity analysis was US$ 132,029.46/quality-adjusted life year, with a 48.02% probability of being cost-effective at willingness-to-pay thresholds of US$ 132,029.22/quality-adjusted life year. The incremental cost-effectiveness ratio remained greater than US$ 80,000/quality-adjusted life year in the deterministic sensitivity analyses. To be more cost-effective and remain below the threshold of 37,653 US$/quality-adjusted life year, which the Chinese population can afford, nivolumab's price would have to be lowered sharply by 53.50%. Nivolumab is clinically beneficial but not cost-effective when compared to chemotherapy. A substantial reduction in nivolumab's drug acquisition cost would be necessary to make it cost-effective for immunotherapy.