Purpose: Results from the LAUNCH trial suggest transarterial chemoembolization (TACE) in combination with lenvatinib is significantly more effective than lenvatinib as a first-line treatment option for advanced hepatocellular carcinoma (HCC). However, the cost of TACE is substantial. This study compares the cost-effectiveness of TACE in combination with lenvatinib (TACE-LEN) with that of lenvatinib alone as the first-line treatment for advanced HCC from the perspective of the Chinese healthcare system.Methods: Markov models of different health states were constructed to simulate first-line treatment, disease progression, and survival in patients with advanced HCC. Clinical efficacy was obtained from the LAUNCH trial. The cost of drugs was sourced from national tender prices, and the treatment cost of weight-decreased was obtained from the Fujian Provincial Bureau of Prices. Other costs and utility values were based on the published literature. Total costs, life years (LYs), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) comprised the model output. One-way and probabilistic sensitivity analyses were performed to validate model robustness and subgroup analyses were also conducted.Results: Analysis of the model showed that compared to lenvatinib, TACE-LEN improved effectiveness by 1.60 QALYs at a total cost increase of $48,874.69, with an ICER value of $30,482.13/QALY. A one-way sensitivity analysis found that the progression-free survival utility value per year had the greatest impact on the model. A probabilistic sensitivity analysis showed that TACE-LEN had a 97.9% probability of being cost-effective as the first-line treatment option for advanced HCC compared to lenvatinib when the willingness-to-pay (WTP) value was $38,201/QALY (three times the Chinese GDP per capita in 2022). Subgroup analysis showed that all subgroups of patients preferred TACE-LEN. However, when the WTP threshold was below $30,300/QALY, TACE-LEN is no longer cost-effective.Conclusion: Our study found TACE-LEN to be a cost-effective treatment option for patients with advanced HCC compared to lenvatinib from a Chinese healthcare system perspective, but not so in low-income provinces in China.

Background: The SPOTLIGHT trial demonstrated that zolbetuximab plus mFOLFOX6 (ZOL-FO) as a first-line regimen compared with placebo plus mFOLFOX6 (PLB-FO) conferred clinical benefits to patients with CLDN18.2-positive, HER2-negative advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. However, due to the high cost of zolbetuximab, whether ZOL-FO is cost-effective compared with PLB-FO is unclear. This study aimed to evaluate the cost-effectiveness of ZOL-FO as a first-line treatment option for CLDN18.2-positive, HER2-negative advanced G/GEJ adenocarcinoma from the perspective of the Chinese healthcare system.Methods: Markov models with three different health states were developed to assess the cost-effectiveness of ZOL-FO as a first-line treatment option for CLDN18.2-positive, HER2-negative advanced G/GEJ adenocarcinoma. Clinical efficacy data were obtained from the SPOTLIGHT trial; the drug’s cost was calculated at national bid prices, and other costs and utility values were obtained from the published literature. Outcomes included total costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). The model’s robustness was verified using one-way sensitivity and probabilistic sensitivity analyses.Results: The ZOL-FO group gained 1.64 QALYs at $87,746.35, while the PLB-FO group gained 1.23 QALYs at $11,947.81. The ICER for ZOL-FO versus PLB-FO was $185,353.28 per QALY gained. The parameters exerting an important impact on the model results were the price of zolbetuximab, body surface area, and progression-free survival utility. At a willingness-to-pay threshold of $38,201/QALY, ZOL-FO had a 0% probability of cost-effectiveness compared with PLB-FO.Conclusion: From the perspective of the Chinese healthcare system, ZOL-FO is unlikely to be cost-effective as the first-line treatment option for CLDN18.2-positive, HER2-negative advanced G/GEJ adenocarcinoma.

Background: Sintilimab plus chemotherapy (SIDCHM) is more effective than placebo plus chemotherapy (PLCHM) for advanced or metastatic esophageal squamous cell carcinoma (ESCC). However, considering the high cost of sintilimab, this study evaluated the cost-effectiveness of SIDCHM in comparison with PLCHM for advanced or metastatic ESCC from the Chinese healthcare system perspective.Methods: Polymorphic Markov models were constructed to simulate the course and cost of SIDCHM. Treatment drug costs were calculated at national list prices and clinical data, other costs, and utility values were extracted from the reference literature. Primary outcomes included quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs). The robustness of the model was verified by one-way sensitivity analysis and probabilistic sensitivity analysis (PSA).Results: SIDCHM obtained 1.03 QALYs at $24,044.49, whereas the effectiveness and cost of PLCHM were 0.67 QALYs and $14,166.24, respectively. The ICER for SIDCHM versus PLCHM was $23,458.08/QALY. The utility of the PFS state was the parameter that had the greatest effect on the ICER. The PSA showed that SIDCHM had an 86% probability of being cost-effective at the willingness-to-pay threshold of 3* Chinese gross domestic product per capita ($37,653/QALY).Conclusion: From the Chinese healthcare system perspective, SIDCHM is considered a cost-effective treatment option compared with PLCHM as first-line therapy for advanced or metastatic ESCC.

Background: The EMPOWER-LUNG 3 clinical trial has shown that cemiplimab plus chemotherapy (CCT) significantly extended overall survival (OS) and progression-free survival (PFS) for patients with advanced non-small cell cancer (NSCLC) compared to placebo plus chemotherapy (PCT). However, the cost-effectiveness of this new treatment option remains unknown. Thus, we evaluated the cost-effectiveness of CCT versus (vs.) PCT as the first-line treatment for patients with advanced NSCLC from the perspective of the Chinese healthcare system.Methods: We constructed a Markov model to evaluate the cost-effectiveness of CCT as the first-line treatment for patients with advanced NSCLC. The transition probabilities were extracted from the survival data of the EMPOWER-LUNG 3 trial. The drugs’ costs were referred from national tender prices, while other model input parameters were derived from the EMPOWER-LUNG 3 trial and published literature. The outcome parameters mainly included quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs). One-way sensitivity analysis and probabilistic sensitivity analysis were performed to evaluate the robustness of the model outcomes.Results: Compared to PCT, in the CCT regimen, an additional $79,667 was spent in terms of the total cost and with an additional 0.31 QALYs, resulting in an ICER value of $253,148/QALY. Sensitivity analysis indicated that the hazard ratio (HR) of OS, the cost of cemiplimab (100 mg), and the HR of PFS, all significantly impacted the model’s results. The probability of CCT (vs. PCT) being cost-effective was 0% at a willingness-to-pay threshold of $38,201/QALYs in China. The scenario analysis showed that when the price of cemiplimab was reduced to less than $184.09/100 mg, the CCT regimen could be considered cost-effective as the first-line treatment for patients with advanced NSCLC compared to the PCT.Conclusion: In China, the CCT was not cost-effective as the first-line treatment for patients with advanced NSCLC.

Background: Results from the GEMSTONE-303 trial indicate that compared with placebo plus capecitabine and oxaliplatin (PLA-CAP), sugemalimab plus capecitabine and oxaliplatin (SUG-CAP) as first-line therapy provides clinical benefits for patients with advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma with programmed cell death ligand 1 (PD-L1) combined positive score (CPS) ≥5. However, the addition of sugemalimab increases medical costs. This study aimed to assess the cost-effectiveness of SUG-CAP vs. PLA-CAP for the first-line treatment of advanced G/GEJ adenocarcinoma with PD-L1 CPS ≥5 from the perspective of China's healthcare system.Methods: A Markov model with three health states was developed to compare the cost-effectiveness of SUG-CAP and PLA-CAP. Clinical data were obtained from the GEMSTONE-303 trial, drug costs were determined based on national bidding prices, and other costs and utility values were obtained from published literature. Outcomes included total costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). Sensitivity analysis was used to verify the robustness of the model.Results: The SUG-CAP incurred costs of $70,673.28 and gained 1.28 QALYs. In the PLA-CAP, the effectiveness was 1.00 QALYs at a cost of $11,241.52. Compared with PLA-CAP, SUG-CAP yielded an increase of 0.28 QALYs at an incremental cost of $59,431.76. The ICER for SUG-CAP vs. PLA-CAP was $217,686.71 per QALY, which exceeds the preset willingness-to-pay (WTP) threshold of $41,511 per QALY, with a 0% probability of being cost-effective. The parameters that significantly affected the model were the cost of sugemalimab, progression-free survival (PFS) utility, and discount rate.Conclusion: From the perspective of China's healthcare system, SUG-CAP as first-line therapy for advanced G/GEJ adenocarcinoma with PD-L1 CPS ≥5 is not cost-effective compared with chemotherapy alone.

Background: PARP inhibitors exhibit significant lethality in tumors with BRCA1/2 mutations or homologous recombination defects; however, their clinical application is limited by the rarity of BRCA1/2 mutations, complex resistance mechanisms, and limited efficacy of monotherapy. Objective: This study aimed to investigate how Niraparib induces dysregulation of sphingolipid metabolism—particularly upregulation of the key enzyme SPHK1—in triple-negative breast cancer (TNBC) cells, and to elucidate a novel super-enhancer (SE)-mediated mechanism of Niraparib resistance. We also applied AI-based virtual screening to identify compounds targeting key nodes and develop strategies for sensitizing TNBC to Niraparib. Results: Niraparib induced sphingolipid metabolic imbalance and significantly upregulated SPHK1 in TNBC. Multi-omics analyses revealed that SPHK1 is regulated by a super-enhancer. Mechanistically, Niraparib inhibited PARylation of the transcription factor SP1, enhancing its occupancy at the SE region and reactivating its transcriptional activity, thereby promoting SPHK1 expression. This process activated pro-survival signaling pathways and conferred niraparib resistance. AI-facilitated virtual screening identified the natural compound Echinatin as a potent SP1 inhibitor, which stably binds to SP1 and exhibits marked synergistic effects with Niraparib. While targeting downstream SPHK1 also provided therapeutic benefit by enhancing the anti-tumor efficacy of Niraparib, Echinatin demonstrates a superior advantage due to its more favorable toxicity profile. Conclusions: Niraparib induces resistance through the SP1-SE-SPHK1 axis, whereas Echinatin effectively reverses this mechanism by inhibiting the upstream regulator SP1, significantly potentiating the efficacy of Niraparib. This study reveals a novel molecular mechanism underlying Niraparib resistance and proposes a promising combination therapy strategy.