Comparison Between Sotorasib with Docetaxel for the Treatment of Chinese Patients with Previously Treated NSCLC with KRASG12C Mutation: A Cost-Effectiveness Analysis to Inform Drug Pricing.

INTRODUCTION: This study sought to investigate the affordable price of sotorasib among patients with previously treated advanced KRASG12C-mutant non-small cell lung cancer (NSCLC) through a cost-effectiveness analysis from the perspectives of both the Chinese healthcare system and the patients. METHODS: We developed a Markov model spanning a 20-year time horizon with a cycle length of 21 days. Our data were derived from the CodeBreaK 200 clinical trial, supplemented with published literature, publicly available national databases, and local hospitals. The primary outcomes were the affordable prices of sotorasib which would result in the incremental cost-effectiveness ratios (ICERs) of sotorasib relative to docetaxel below the preset willing-to-pay (WTP) threshold. Sensitivity analyses were performed to evaluate the model's robustness. RESULTS: At the national level, from the perspective of the Chinese healthcare system and patients, the price of sotorasib should be lower than US$0.04673 and $0.03231, respectively, to make it affordable, which is equivalent to $1346 and $931 per box (120 mg × 240 pieces). At the provincial level, the price ceiling of sotorasib/mg fluctuated between $0.04084 to $0.08061 from the Chinese healthcare system's perspective and between $0.02642 to $0.06620 from the patients' perspective. Probabilistic sensitivity analyses revealed that, as the price of sotorasib decreased, its likelihood of being cost-effective increased. CONCLUSION: Sotorasib might be a cost-effective therapy in China. The pharmaco-economic evidence generated from this study has significant implications not only for guiding the drug pricing of the upcoming sotorasib but also for determining the reimbursement ratio for its potential inclusion in the National Reimbursement Drugs List in the future.

An accurate calculation method for inductor air gap length in high power DC-DC converters.

High-power inductors are fundamental components in high-power DC-DC converters, with their performance being a crucial metric of converter efficiency. This paper presents an in-depth analysis of a novel calculation method for the air gap length in such inductors. Taking into account the effects of air gap diffusion and the winding magnetic field, an expression for the air gap diffusion radius is derived, focusing on a distributed air gap structure. Furthermore, models for calculating the air gap and winding reluctance are developed, grounded in electromagnetic field theory. An equivalent magnetic circuit model, formulated based on Kirchhoff's second law, facilitates the proposed method for air gap length calculation. This study also involves the development of 3D models for both discrete and decoupled integrated inductors. The comparison between simulation outcomes and calculated air gap lengths indicates a maximum error of less than 8%, with the minimum error being as low as - 0.79%. Compared with traditional methods, the calculation method proposed in this paper has significant advantages. Additionally, the discrepancy between calculated values and experimental measurements is found to be 1.11%. These results validate the accuracy and applicability of the theoretical analysis and calculation method, underscoring their significance in the design and optimization of high-power DC-DC converters.

A study on whether deep learning models based on CT images for bone density classification and prediction can be used for opportunistic osteoporosis screening.

This study utilized deep learning to classify osteoporosis and predict bone density using opportunistic CT scans and independently tested the models on data from different hospitals and equipment. Results showed high accuracy and strong correlation with QCT results, showing promise for expanding osteoporosis screening and reducing unnecessary radiation and costs. PURPOSE: To explore the feasibility of using deep learning to establish a model for osteoporosis classification and bone density value prediction based on opportunistic CT scans and to verify its generalization and diagnostic ability using an independent test set. METHODS: A total of 1219 cases of opportunistic CT scans were included in this study, with QCT results as the reference standard. The training set: test set: independent test set ratio was 703: 176: 340, and the independent test set data of 340 cases were from 3 different hospitals and 4 different CT scanners. The VB-Net structure automatic segmentation model was used to segment the trabecular bone, and DenseNet was used to establish a three-classification model and bone density value prediction regression model. The performance parameters of the models were calculated and evaluated. RESULTS: The ROC curves showed that the mean AUCs of the three-category classification model for categorizing cases into "normal," "osteopenia," and "osteoporosis" for the training set, test set, and independent test set were 0.999, 0.970, and 0.933, respectively. The F1 score, accuracy, precision, recall, precision, and specificity of the test set were 0.903, 0.909, 0.899, 0.908, and 0.956, respectively, and those of the independent test set were 0.798, 0.815, 0.792, 0.81, and 0.899, respectively. The MAEs of the bone density prediction regression model in the training set, test set, and independent test set were 3.15, 6.303, and 10.257, respectively, and the RMSEs were 4.127, 8.561, and 13.507, respectively. The R-squared values were 0.991, 0.962, and 0.878, respectively. The Pearson correlation coefficients were 0.996, 0.981, and 0.94, respectively, and the p values were all < 0.001. The predicted values and bone density values were highly positively correlated, and there was a significant linear relationship. CONCLUSION: Using deep learning neural networks to process opportunistic CT scan images of the body can accurately predict bone density values and perform bone density three-classification diagnosis, which can reduce the radiation risk, economic consumption, and time consumption brought by specialized bone density measurement, expand the scope of osteoporosis screening, and have broad application prospects.

The Effect of Dezocine on the Median Effective Dose of Sufentanil-Induced Respiratory Depression in Patients Undergoing Spinal Anesthesia Combined with Low-Dose Dexmedetomidine.

Purpose: The application of sedation and analgesia in spinal anesthesia has many benefits, but the risk of respiratory depression (RD) caused by opioids cannot be ignored. We aimed to observe the effect of dezocine, a partial agonist of µ-receptor, on the median effective dose (ED50) of sufentanil-induced RD in patients undergoing spinal anesthesia combined with low-dose dexmedetomidine. Patients and Methods: Sixty-two patients were randomly assigned to dezocine group (DS) and control group (MS). After spinal anesthesia, mask oxygen (5 L/min) and dexmedetomidine (0.1 ug/kg) were given. Five minutes later, patients in the DS group received an Intravenous (IV) bolus of sufentanil and 0.05mg/kg dezocine, while patients in the MS group only received an IV bolus of sufentanil. Results: ED50 of DS group was 0.342 ug/kg, 95% confidence interval (CI) was (0.269, 0.623) ug/kg, and the ED50 of MS group was 0.291 ug/kg, 95% CI was (0.257, 0.346) ug/kg. There was no difference in the type and treatment measures of RD and hemodynamic changes between the two groups, and no serious adverse reactions occurred in either group. Conclusion: Dezocine can improve RD induced by sufentanil in patients with spinal anesthesia combined with low-dose dexmedetomidine, and increase the safety window of sufentanil use.

Spatholobus suberectus inhibits lipogenesis and tumorigenesis in triple-negative breast cancer via activation of AMPK-ACC and K-Ras-ERK signaling pathway.

Background and aim: Triple-negative breast cancer (TNBC) is a highly invasive type of breast cancer with a poor prognosis. Currently, there are no effective management strategies for TNBC. Earlier, our lab reported the percolation of Spatholobus suberectus for the treatment of breast cancer. Lipid metabolic reprogramming is a hallmark of cancer. However, the anti-TNBC efficiency of S. suberectus extract and its causal mechanism for preventing lipogenesis have not been fully recognized. Hence, the present study aimed to investigate the inhibitory role of S. suberectus extract on lipogenesis and tumorigenesis in TNBC in vitro and in vivo by activating AMPK-ACC and K-Ras-ERK signaling pathways using lipidomic and metabolomic techniques. Experimental procedure: Dried stems of S. suberectus extract inhibited lipogenesis and tumorigenesis and promoted fatty acid oxidation as demonstrated by the identification of the metabolites and fatty acid markers using proteomic and metabolomic analysis, qPCR, and Western blot. Results and conclusion: The results indicated that S. suberectus extract promotes fatty acid oxidation and suppresses lipogenic metabolites and biomarkers, thereby preventing tumorigenesis via the AMPK-ACC and K-Ras-ERK signaling pathways. On the basis of this preclinical evidence, we suggest that this study represents a milestone and complements Chinese medicine. Further studies remain underway in our laboratory to elucidate the active principles of S. suberectus extract. This study suggests that S. suberectus extract could be a promising therapy for TNBC.

[18 F] -FAPI-42 PET/CT assessment of Progressive right ventricle fibrosis under pressure overload.

BACKGROUND: Right heart failure (RHF) is a complication of pulmonary hypertension (PH) and increases the mortality independently of the underlying disease. However, the process of RHF development and progression is not fully understood. We aimed to develop effective approaches for early diagnosis and precise evaluation of RHF. METHODS: Right ventricle (RV) pressure overload was performed via pulmonary artery banding (PAB) surgery in Sprague-Dawley (SD) rats to induce RHF. Echocardiography, right heart catheterization, histological staining, fibroblast activation protein (FAP) immunofluorescence and 18 F-labelled FAP inhibitor-42 ([18 F] -FAPI-42) positron emission tomography/computed tomography (PET/CT) were performed at day 3, week 1, 2, 4 and 8 after PAB. RNA sequencing was performed to explore molecular alterations between PAB and sham group at week 2 and week 4 after PAB respectively. RESULTS: RV hemodynamic disorders were aggravated, and RV function was declined based on right heart catheterization and echocardiography at week 2, 4 and 8 after PAB. Progressive cardiac hypertrophy, fibrosis and capillary rarefaction could be observed in RV from 2 to 8 weeks after PAB. RNA sequencing indicated 80 upregulated genes and 43 downregulated genes in the RV at both week 2 and week 4 after PAB; Gene Ontology (GO) analysis revealed that fibrosis as the most significant biological process in the RV under pressure overload. Immunofluorescence indicated that FAP was upregulated in the RV from week 2 to week 8 after PAB; and [18 F] -FAPI-42 PET/CT revealed FAPI uptake was significantly higher in RV at week 2 and further increased at week 4 and 8 after PAB. CONCLUSION: RV function is progressively declined with fibrosis as the most prominent molecular change after pressure overload, and [18 F] -FAPI-42 PET/CT is as sensitive and accurate as histopathology in RV fibrosis evaluation.

Manipulating the Solvation Structure and Interface via a Bio-Based Green Additive for Highly Stable Zn Metal Anode.

The practical application of aqueous zinc-ion batteries (AZIBs) is limited by serious side reactions, such as the hydrogen evolution reaction and Zn dendrite growth. Here, the study proposes a novel adoption of a biodegradable electrolyte additive, γ-Valerolactone (GVL), with only 1 vol.% addition (GVL-to-H2 O volume ratio) to enable a stable Zn metal anode. The combination of experimental characterizations and theoretical calculations verifies that the green GVL additive can competitively engage the solvated structure of Zn2+ via replacing a H2 O molecule from [Zn(H2 O)6 ]2+ , which can efficiently reduce the reactivity of water and inhibit the subsequent side reactions. Additionally, GVL molecules are preferentially adsorbed on the surface of Zn to regulate the uniform Zn deposition and suppress the Zn dendrite growth. Consequently, the Zn anode exhibits boosted stability with ultralong cycle lifespan (over 3500 h) and high reversibility with 99.69% Coulombic efficiency. The Zn||MnO2 full batteries with ZnSO4 -GVL electrolyte show a high capacity of 219 mAh g-1 at 0.5 A g-1 and improved capacity retention of 78% after 550 cycles. This work provides inspiration on bio-based electrolyte additives for aqueous battery chemistry and promotes the practical application of AZIBs.

GABRP is a Promising Prognostic Biomarker and Associated with Immune Cell Infiltration in Lung Squamous Cell Carcinoma.

Background: GABRP has been reported to play an oncogenic role in various carcinomas. However, no report has been found for its involvement in lung squamous cell carcinoma (LUSC) development yet. We aimed to explore the expression and prognostic roles of GABRP and assessment of its association with tumor microenvironment in LUSC. Methods: The GABRP expression in LUSC was analyzed using TCGA, GEO, and HPA databases. The Kaplan-Meier, Cox regression analysis, and receiver operating characteristic (ROC) curve were applied to assess the prognostic and diagnostic values of GABRP in LUSC. We also performed ESTIMATE and ssGSEA to explore the association between GABRP expression and immune cell infiltrations. GABRP was highly expressed in LUSC patients, and up-regulation of GABRP was associated with shorter overall survival (OS). Cox regression analysis indicated that GABRP was an independent prognostic factor for LUSC patients. KEGG analysis revealed that GABRP may play an important role in starch and sucrose metabolism and nicotine addiction. Specifically, GABRP expression showed significant positive correlations with the infiltration levels of most types of immune cells, as well as immune checkpoint molecules expression. Conclusion: Up-regulation of GABRP in LUSC could be severed as a prognostic marker and a potential target for immunotherapy in LUSC.

First-line systemic treatment strategies for unresectable hepatocellular carcinoma: A cost-effectiveness analysis.

BACKGROUND: Oral multikinase inhibitors and immune checkpoint inhibitors (ICIs) are effective for treating advanced hepatocellular carcinoma (aHCC) but may increase cost. This study compared the cost-effectiveness of oral multikinase inhibitors and ICIs in the first-line treatment of patients with aHCC. METHODS: A three-state Markov model was established to study the cost-effectiveness of drug treatment from the perspective of Chinese payers. The key outcomes in this study were total cost, quality-adjusted life years (QALYs), and the incremental cost-effectiveness ratio (ICER). RESULTS: The total costs and QALYs of sorafenib, sunitinib, donafenib, lenvatinib, sorafenib plus erlotinib, linifanib, brivanib, sintilimab plus IBI305, and atezolizumab plus bevacizumab were $9070 and 0.25, $9362 and 0.78, $33,814 and 0.45, $49,120 and 0.83, $63,064 and 0.81, $74,814 and 0.82, $81,995 and 0.82, $74083 and 0.85, and $104,188 and 0.84, respectively. The drug regimen with the lowest ICER was sunitinib ($551 per QALY), followed by lenvatinib ($68,869 per QALY). For oral multikinase inhibitors, the ICER of lenvatinib, sorafenib plus erlotinib, linifanib and brivanib compared with sunitinib was $779576, $1534,347, $1768,971, and $1963,064, respectively. For ICIs, sintilimab plus IBI305 is more cost effective than atezolizumab plus bevacizumab. The model was most sensitive to the price of sorafenib, the utility of PD, and the price of second-line drugs. CONCLUSION: For oral multikinase inhibitors, the order of possible treatment options is sunitinib > lenvatinib > sorafenib plus erlotinib > linifanib > brivanib > donafenib. For ICIs, the order of possible treatment options is sintilimab plus IBI305 > atezolizumab plus bevacizumab.

Dynamic zero-COVID strategy in controlling COVID-19 in Shanghai, China: A cost-effectiveness analysis.

BACKGROUND: The sustainability and generalizability of China's dynamic zero-COVID strategy on eliminating SARS-CoV-2 transmission has casted doubt globally, mainly because it has exacted high social and economic cost. This study aimed to estimate the disease burden during the first wave of Omicron in China and compared the cost-effectiveness of implementing a Real-world strategy (adjusted dynamic zero-COVID strategy) with two simulated strategies (routine and stricter dynamic zero-COVID strategy) to inform appropriate strategies for COVID-19 pandemic control. METHODS: A dynamic state-transition simulation model was developed to compare the health and cost outcomes between different dynamic zero-COVID strategies. Omicron-related healthcare costs were estimated from the societal perspective. Epidemiological parameter values were derived from data of real-world or generated by model calibration; costs and effectiveness parameter values were informed either by local data or published literature. The primary outcomes were total social cost, disability adjusted life-years (DALYs) and net monetary benefit (NMB). Deterministic sensitivity analyses (DSA) and scenario analyses were performed to assess the model robustness. RESULTS: The first wave of Omicron in Shanghai resulted in 47,646 DALYs lost and 415 billion RMB losses. At a willingness-to-pay threshold of 173,630 RMB (the GDP per capita of Shanghai in 2021) per DALY saved, the Real-world strategy was considered as the most cost-effective strategy due to its highest NMB (-407 billion). Results from DSA confirmed the robustness of our findings. CONCLUSION: Our finding supported the Real-world strategy taken by the Shanghai Municipal Government between March 1 and May 21, 2022 to control the first wave of Omicron outbreak. Moreover, our results indicated that whether the Stricter dynamic zero-COVID strategy is worth implementing at the beginning of the COVID-19 outbreak mainly depended on the infection rate of COVID-19 among primary contacts. Our analysis provides important evidence to inform policy makers to make appropriate decisions regarding COVID-19 pandemic management.

The complete chloroplast genome and phylogenetic analysis of Christella dentata (Forssk.) Brownsey & Jermy (Thelypteridaceae).

Christella dentata (Forssk.) Brownsey & Jermy (Thelypteridaceae) is endemic to the tropical and subtropical regions of Africa, Asia, and Asia Pacific. In this study, the complete chloroplast genome sequence of C. dentata was assembled using next-generation sequencing data. The complete chloroplast genome was 151,662 bp in length and had a typical quadripartite structure, which consisted of a small single-copy region (21,776 bp) and a large single-copy region (82,624 bp) that were separated by a pair of inverted repeats (23,631 bp each). A total of 131 genes were predicted, including 89 protein coding (CDS), 34 tRNA, and eight rRNA genes. The overall GC content of the chloroplast genome was 42.48%. Based on the concatenated shared unique CDS sequence dataset, phylogenetic analysis using both the maximum-likelihood and the Bayesian inference methods revealed that C. dentata is placed within Thelypteridaceae and is closely related to Christella appendiculata. Such genetic information would be useful for studies on the evolution pattern in ferns. The availability of chloroplast genome sequence for the species also paves the way to resolving the complicated relationship among members of Christella.

Label-free Aptasensor for the Ultrasensitive Detection of Insulin Via a Synergistic Fluorescent Turn-on Strategy Based on G-quadruplex and AIEgens.

Insulin, the only hormone regulating blood glucose level, is strongly associated with diabetes and its complications. Specific recognition and ultrasensitive detection of insulin are of clinical significance for the early diagnosis and treatment of diabetes. Inspired by aggregation-induced emission, we presented a turn-on label-free fluorescence aptasensor for insulin detection. Quaternized tetraphenylethene salt was synthesized as the fluorescence probe. Guanine-rich aptamer IGA3 was selected as recognition element. Graphene oxide was chosen as the quencher. Under optimized conditions, the fluorescence aptasensor displayed a wide linear range (1.0 pM-1.0 µM) with a low limit of detection (0.42 pM). Furthermore, the aptasensor was successfully applied to detect insulin in human serum. Spiked recoveries were obtained in the range of 96.06%-104.26%. All these results demonstrated that the proposed approach has potential application in the clinical diagnostics of diabetes.

Economic evaluation of FLOT and ECF/ECX perioperative chemotherapy in patients with resectable gastric or gastro-oesophageal junction adenocarcinoma.

OBJECTIVE: The perioperative chemotherapy with fluorouracil, leucovorin, oxaliplatin plus docetaxel (FLOT) was recommended by the Chinese Society of Clinical Oncology Guidelines for gastric cancer (2018 edition) for patients with resectable gastric or gastro-oesophageal junction adenocarcinoma (class IIA). However, the economic impact of FLOT chemotherapy in China remains unclear. The analysis aimed to compare the cost-effectiveness of FLOT versus epirubicin, cisplatin plus fluorouracil or capecitabine (ECF/ECX) in patients with locally advanced resectable tumours. DESIGN: We developed a Markov model to compare the healthcare and economic outcomes of FLOT and ECF/ECX in patients with resectable gastric or gastro-oesophageal junction adenocarcinoma. Costs were estimated from the perspective of Chinese healthcare system. Clinical and utility inputs were derived from the FLOT4 phase II/III clinical trial and published literature. Sensitivity analyses were employed to assess the robustness of our result. The annual discount rate for costs and health outcomes was set at 5%. OUTCOME MEASURES: The primary outcome of incremental cost-effectiveness ratios (ICERs) was calculated as the cost per quality-adjusted life years (QALYs). RESULTS: The base-case analysis found that compared with ECF/ECX, the use of FLOT chemotherapy was associated with an additional 1.08 QALYs, resulting in an ICER of US$851/QALY. One-way sensitivity analysis results suggested that the HR of overall survival and progression-free survival had the greatest impact on the ICER. Probabilistic sensitivity analysis demonstrated that FLOT was more likely to be cost-effective compared with ECF/ECX at a willingness-to-pay threshold of US$31 513/QALY. CONCLUSIONS: For patients with locally advanced resectable tumours, the FLOT chemotherapy is a cost-effective treatment option compared with ECF/ECX in China. TRIAL REGISTRATION NUMBER: NCT01216644.

Alpha emitter radium-223 in patients with metastatic castration-resistant prostate cancer: A cost-utility analysis.

Objective: To assess the cost effectiveness of radium-223 dichloride for patients with metastatic castration-resistant prostate cancer (mCRPC) in China. Materials and methods: A Markov model was developed to estimate the long-term health and economic outcomes of radium-223 plus best standard care (BSC) treatment and BSC only for bone mCRPC patients over a lifetime horizon. The patients and interventions were modeled according to the ALSYMPCA trial. Costs were collected from a Chinese health system perspective. Utility values were derived from the published literature. The base-case model results were quality-adjusted life year (QALY), total cost, and incremental cost-utility ratio (ICUR). Uncertainty analyses were performed to assess the robustness of our conclusions. Results: Compared with the BSC arm, radium-223 achieved an excess 0.344 QALYs with an incremental cost of $29,459, resulting in an ICUR of $85,647 per QALY. The probability of Ra-223 being cost effective for the patients with bone mCRPC was sharply low (<0.5%) at a willingness-to-pay threshold of $38,136/QALY. Uncertainty analyses revealed that the model is robust to all the input parameters. Conclusion: Radium-223 is unlikely to be cost effective in patients with bone mCRPC at the current WTP threshold, from a Chinese health system perspective. In affluent areas with a high per-capita GDP, radium-223 therapy may be cost effective.

Propagation characteristics and prediction of airblast overpressure outside tunnel: a case study.

The drilling and blasting method is widely used in tunnel engineering. The accompanying airblast may damage structures and annoy nearby occupants. The prediction of airblast overpressure (poa) outside the tunnel is necessary to improve the safety of blasting works. A study of propagation characteristics of airblasts induced by tunnel blasting was carried out through experimental and numerical studies. The results indicate that the distributions of the poa outside the tunnel were anisotropic, which does not conform to the decay law of an explosion in free-field. The propagation of airblasts induced by tunnel blasting is related to the airblast shape. The phenomenon that the poa along the axial direction of the tunnel was higher than along other directions can be explained by the numerical results of the process of airblasts. The airblasts outside the tunnel traveled as a spherical wave, but the pressure was not uniformly distributed. After an airblast plane wave with high speed and high pressure inside the tunnel was transmitted out of the tunnel, its inertia strengthened the pressure in the axial direction. The airblast outside the tunnel is related to the propagation distance Rout, the angle from the measurement to the tunnel axis α, and the pressure intensity p0 at the tunnel portal. Subsequently, an ellipsoidal contour curve of the poa outside the tunnel was plotted, and therefore a new prediction equation was validated by numerical results and field data. Finally, the newly proposed methodology guided the blast design.

Lung cancer screening with low-dose computed tomography: National expenditures and cost-effectiveness.

Objective: To compare the cost-effectiveness of undertaking low-dose computed tomography (LDCT) screening for early detection of lung cancer (LC) with different frequencies within the healthcare system of China, and estimate the additional national healthcare expenditure and five-year LC mortality associated with different screening frequencies. Material and methods: A Markov model was established using national LC epidemiological data from the Chinese Center for Disease Control and Prevention, demographic data from the Chinese Statistical Yearbook, and cost and effectiveness data mainly from the Cancer Screening Program in China. The model included thirty sex-specific screening strategies, which were classified by initial screening age (30, 35, 40, 45, and 50), and screening intervals (intervals at single time point, 1, 2, 5, 10, and 20 years). The main model outputs were incremental cost-effectiveness ratios (ICERs), additional national healthcare expenditure and five-year LC mortality. Results: The ICERs for LDCT screening strategies vs. non-screening strategy ranged from $16,086 per quality-adjusted life-year (QALY) to $3,675,491 per QALY in the male cohort, and from $36,624 per QALY to $5,943,556 per QALY in the female cohort. The annual increment national healthcare expenditures related to LDCT screening were varied from $0.25 to $13.39 billion, with the lower cost in the cohort with older screening ages and lower screening frequencies. More frequent screening with LDCT was associated with a greater reduction in LC death: an annual LDCT screening was linked to an estimated reduction in five-year LC death by 27.27-29.07%, while a one-off screening was linked to a reduction by 5.56-5.83%. Conclusion: Under a willingness-to-pay (WTP) threshold of three times the Chinese gross domestic product (GDP) per capita (US $37,654), annual screening with an initiating age at 50 was most cost-effective in both male and female cohorts. By taking into account both the national healthcare expenditures and the effect of LDCT screening, our study results support undertaking LDCT screening annually from 50 years old in general populations.

Cost-effectiveness of ensartinib, crizotinib, ceritinib, alectinib, brigatinib and lorlatinib in patients with anaplastic lymphoma kinase-positive non-small cell lung cancer in China.

Objective: Six anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKIs), including one domestic (ensartinib) and five imported ALK-TKIs (crizotinib, ceritinib, alectinib, brigatinib, and lorlatinib), have been recommended as first-line treatments for advanced ALK-positive NSCLC in China. This study sought to examine the cost-effectiveness of these six novel therapies in Chinese patients. Material and methods: We constructed a Markov model to compare the cost-effectiveness of the six ALK-TKIs as a first-line treatment for patients with advanced ALK-positive NSCLC from the perspective of the Chinese healthcare system. Transition probabilities were estimated by synthesizing data from the PROFILE 1,029 trial and a network meta-analysis. Health state utilities and costs were sourced from published literature, publicly available national databases, and local general hospitals. The robustness of model was assessed via deterministic sensitivity analyses and probabilistic sensitivity analyses. Results: Compared with crizotinib, ensartinib achieved additional 0.12 quality-adjusted life-year (QALY) with marginal costs of $3,249, resulting in an incremental cost-effectiveness ratio (ICER) of $27,553/ QALY. When compared with ceritinib and brigatinib, ensartinib achieved additional 0.06 and 0.03 QALYs with substantially reduced costs. When compared with lorlatinib and alectinib, ensartinib was associated with a lower QALY and decreased total costs; the ICERs for lorlatinib and alectinib were $934,101/ QALY and $164,888/ QALY, respectively. Conclusion: For Chinese patients with advanced ALK-positive NSCLC, ensartinib was a cost-effective option compared with crizotinib, and was a dominant alternative to ceritinib and brigatinib. Although lorlatinib and alectinib were associated with prolonged survival compared with ensartinib, they were less cost-effective than ensartinib due to the overwhelming total costs.

Cost-effectiveness analysis of tislelizumab, nivolumab and docetaxel as second- and third-line for advanced or metastatic non-small cell lung cancer in China.

Objective: Domestic PD-1inhibitor tislelizumab has emerged as a promising treatment for Chinese patients with driver-negative advanced or metastatic non-small cell lung cancer (NSCLC). The purpose of our study to evaluate whether tislelizumab is cost-effective as a second- or third-line treatment for this population compared with docetaxel (conventional chemotherapy) and nivolumab (imported PD-1inhibitor), from the perspective of the Chinese healthcare system. Material and Methods: A Markov model with a 3-week Markov cycle and a 30-year time horizon was built to compare the cost-effectiveness of second- or third-line tislelizumab versus docetaxel and nivolumab. Transition probabilities, including disease progression, survival, and adverse events (AEs)-related treatment discontinuation event, were estimated from the clinical trials. Costs and health utilities were collected from local hospitals, public database and published literature. Results: Compared with docetaxel, tislelizumab provided an additional 0.33 quality-adjusted life-years (QALYs) (1.37 vs. 1.04 QALYs) at an incremental cost of $9,286 ($23,646 vs. $14,360) for Chinese patients with driver-negative advanced or metastatic NSCLC, resulting in an incremental cost-effectiveness ratio (ICER) of $27,959/QALY under the WTP threshold of $35,663/QALY used in the model. Compared with nivolumab, tislelizumab was associated with a lower cost ($23,646 vs. $59,447) and higher QALYs (1.37 vs. 1.20 QALYs), resulting in its dominance of nivolumab. Conclusion: From the perspective of the Chinese healthcare system, domestic PD-1inhibitor tislelizumab immunotherapy represents a cost-effective treatment strategy compared with conventional docetaxel chemotherapy and imported PD-1inhibitor nivolumab immunotherapy in the treatment of driver-negative advanced or metastatic NSCLC beyond the first-line setting. In the era of "Universal Medical Insurance System", the rational use of domestic anticancer drugs guided by cost-benefit evidence would be an effective means to balance the limited expenditure of medical insurance fund and the growing demand for cancer treatments.

The Cost-Effectiveness of Tislelizumab Plus Chemotherapy for Locally Advanced or Metastatic Nonsquamous Non-Small Cell Lung Cancer.

Objective: To investigate the cost-effectiveness of adding Chinese-developed anti-PD-1 antibody tislelizumab to first-line pemetrexed-platinum chemotherapy in (1) a study population of patients with locally advanced or metastatic nonsquamous non-small cell lung cancer (nsqNSCLC) and without known sensitizing EGFR mutations or ALK rearrangements and (2) its subgroups from the perspective of Chinese healthcare system. Material and Methods: Separate Markov models were constructed for the entire study population and its subgroups; 10,000 patients with locally advanced or metastatic nsqNSCLC and without driver gene mutations were simulated in the first-line tislelizumab plus pemetrexed-platinum (TPP) arm and first-line pemetrexed-platinum (PP) arm, respectively. Transition probabilities were extracted from the RATIONALE 304 trial. Public health state utilities and costs were obtained from published literature, public national databases, and local general hospitals. The main outputs were incremental cost-effectiveness ratios (ICERs). The ICERs were compared to a willingness-to-pay threshold of $35,663 per quality-adjusted life-years (QALYs) to determine the cost-effective treatment. Sensitivity analyses were employed to assess the uncertainty in the model. Results: For the entire patient population, first-line TPP versus PP use increased the effectiveness by 0.99 QALYs and healthcare costs by $28,749, resulting in an ICER of $28,749/QALY that was lower than the prespecified WTP threshold. For patient subgroups, first-line TPP conferred the greatest survival benefit in patients with PD-L1 expression ≥50%, followed by patients with liver metastasis and those who are current or former smokers. Overall, the ICERs for the first-line TPP versus PP ranged from $27,018/QALYs to $33,074/QALYs, which were consistently below the WTP threshold. Conclusion: For Chinese patients with locally advanced or metastatic nsqNSCLC who had no known sensitizing EGFR mutations or ALK rearrangements, adding the Chinese-developed anti-PD-1 antibody tislelizumab to the first-line pemetrexed-platinum chemotherapy was cost-effective regardless of their baseline characteristics.