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.

Development of a rhodamine-based fluorescent probe for ATP detection for potential applications in meat freshness assessment.

Adenosine triphosphate (ATP) plays a vital role in physiological processes and is an essential indicator of microbial content in food. Herein, a new sensitive, rapid and water-soluble probe for ATP detection was developed. Rhodamine B and pentaethylenehexamine were employed to design and synthesise the probe rhodamine-pentaethylenehexamine (RP) for selective ATP detection. The synthesised probe RP was characterized using Fourier transform infrared, NMR and dynamic light scattering size distributions. Upon the addition of ATP, the probe exhibited a distinct change in fluorescence intensity, with fluorescence emission at 580 nm. A linear relationship was observed between fluorescence intensity and ATP concentrations at 0-50 µmol/L, with a limit of detection of 10.97 × 10-9 mol/L. The results of the zeta potential and molecular dynamics simulation demonstrated that the detection mechanism of the probe RP is associated with the electrostatic adsorption interaction between the multi-positively charged sites of RP and the negatively charged triphosphate structure of ATP. Our study provides new insights into improving charge site identification in small molecule detection. Furthermore, the successful detection of ATP on meat surfaces indicates that RP has the potential to assess meat freshness.

Cost-effectiveness analysis of anlotinib versus sunitinib as first-line treatment for metastatic renal cell carcinoma in China.

BACKGROUND: Sunitinib was approved several years ago as a first-line drug for treating metastatic renal cell carcinoma (mRCC); however, its high price and broad side effects when administered at the standard dose have limited its clinical use. A clinical trial (NCT02072031) confirmed that anlotinib could be used as the first-line treatment for mRCC. This study was conducted to evaluate the cost-effectiveness of anlotinib as a first-line treatment for mRCC compared to that of sunitinib in China. METHODS: A Markov model was established to compare the cost-effectiveness of anlotinib with that of sunitinib. Clinical data were obtained from a multi-center phase II trial (clinical trial information: NCT02072031). Utility values were obtained from the literature. Total costs were calculated from a Chinese societal perspective. A sensitivity analysis was conducted to assess the model uncertainty. The life-year (LY), quality-adjusted life-year (QALY), and incremental cost-effectiveness ratio were calculated. RESULTS: The base-case analysis over a lifetime horizon of 10 years showed that the anlotinib group had 2.196 LYs and 1.487 QALYs at a total cost of $68,597.84. The sunitinib group had 2.194 LYs and 1.432 QALYs at a total cost of $88,060.02. This resulted in incremental cost-effectiveness ratios (ICER) of anlotinib versus sunitinib of $-9,210,858.93 per LYs and $-354,117.07 per QALYs, suggesting that anlotinib is a more effective and less costly strategy than sunitinib. CONCLUSION: Anlotinib may be a more cost-effective first-line treatment strategy for mRCC than sunitinib in China.