Drug Pricing of Domestic Anti-PD-L1 Antibody Adebrelimab: Cost-Effectiveness Analysis of the First-Line ES-SCLC Treatment in China.

Purpose: The market price of adebrelimab, the first Chinese-developed anti-PD-L1 antibody used as a first-line treatment for extensive stage-small-cell lung cancer (ES-SCLC), has garnered significant public attention. This study sought to investigate the affordable price of adebrelimab for Chinese patients with untreated ES-SCLC through a cost-effectiveness analysis. Patients and Methods: We conducted a cost-effectiveness analysis using a Markov model, incorporating a what-if scenario of adding adebrelimab to first-line etoposide/platinum (EP) chemotherapy is cost-effective for ES-SCLC patients from the perspective of the Chinese healthcare system. The model included three mutually exclusive health states, with transition probabilities derived from the CAPSTONE-1 trial. Health state utilities and costs were acquired from a myriad of authoritative sources. We compared the incremental cost-effectiveness ratios (ICERs) for adebrelimab plus EP chemotherapy (AEP) versus EP with a willingness-to-pay threshold of $37,654 per quality-adjusted life-years (QALYs) to estimate the affordable price ceiling of the upcoming adebrelimab. Results: For the entire ES-SCLC population, the estimated price ceiling of adebrelimab/mg was $0.542 (95% CI, $0.542-$0.552). Subgroup analyses found that the highest price ceiling of adebrelimab/mg was observed in ES-SCLC patients with lactate dehydrogenase concentration ≤ upper normal limit [$0.824 (95% CI, $0.815-$0.830)]; and the lowest was found in ES-SCLC patients with liver metastasis [$0.252 (95% CI, $0.250- $0.256)]. Sensitivity analysis revealed a heightened probability of cost-effectiveness for the first-line AEP as the price of adebrelimab decreased, encompassing both the entire ES-SCLC population and its subgroups. Conclusion: The affordable price range for adebrelimab/mg Chinese patients with untreated ES-SCLC was estimated to be between $0.252 and $0.824, with variations observed across different subgroups. In the context of universal healthcare coverage, our study provides valuable evidence to inform the implementation of a value-based pricing strategy for cancer treatment.

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.

Prognostic significance of metformin treatment in endometrial cancer: a meta-analysis.

Background: Previous studies suggested that metformin treatment could affect the survival outcomes of endometrial cancer (EC). This meta-analysis aims to investigate the prognostic value of metformin use in patients with EC. Methods: Pubmed and Embase databases were searched from inception to November 2019. We analyzed the association between metformin intake and survival of EC. Summary hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using the random-effects model. The primary outcome was overall survival (OS) and the secondary outcome was progression-free survival (PFS). Results: A total of eight cohort studies enrolling 6911 participants were eligible for this meta-analysis. For patients with diabetes mellitus (DM), the pooled results showed metformin could significantly improve the OS (HR=0.57, 95% CI 0.42 to 0.78) and PFS (HR=0.61, 95% CI 0.46 to 0.80,). However, no significant difference in OS (HR= 0.79, 95% CI 0.58 to 1.08) and PFS (HR=1.05, 95% CI 0.93 to1.19) was found between the patients with diabetes who used metformin and the subjects without diabetes. Conclusions: This study showed, based on only a limited number of studies, that metformin use was significantly associated a favorable survival outcome with of EC in diabetes patients.

Osteogenesis activity of isocoumarin a through the activation of the PI3K-Akt/Erk cascade-activated BMP/RUNX2 signaling pathway.

Bone formation refers to a series of complex events related to the activities of osteoblasts. In this study, we evaluated the osteogenesis activity of a natural compound named isocoumarin A that was isolated from the rhizomes of Polygonum amplexicaule on the non-transformed preosteoblastic cell line MC3T3-E1 for an in vitro study, and the results revealed that it increased the proliferation and promoted the mineralization of the extracellular matrix of MC3T3-E1 cells after treatment for 3 d in a dose-dependent manner. The cell metabolic activity peaked at 169% at 10 µM, and the activity of alkaline phosphatase (ALP) tripled to 15.94 U/mg compared with the control group. The protein levels of morphogenetic protein 2 (BMP-2), runt-related transcription factor 2 (RUNX2), ALP, and the mRNA levels of ALP, type I collagen (COL-1), and osteocalcin (OCN) were also upregulated after isocoumarin A administration. The mechanism investigation revealed that these effects were associated with the activation of the p-Akt/p-Erk1/2-activated BMP/RUNX2 signaling pathway. Subsequently, the in vivo investigation on the zebrafish embryos model demonstrated that isocoumarin A (0.30 mM) increased the number of vertebrae (5.38 ±â€¯2.07 pcs) and the vertebral area (433.25 ±â€¯111.77 µm2) in the development process of zebrafish embryos after a 7-day postfertilization (dpf) culture compared with the control group (2.50 ±â€¯1.16 pcs and 209.75 ±â€¯86.40 µm2). Together, these results indicated that isocoumarin A could be viewed as a promising candidate in early drug discovery and development to promote the healing of fractures and postmenopausal osteoporosis.

Prognostic significance of anti-diabetic medications in pancreatic cancer: A meta-analysis.

The role of anti-diabetic medications in pancreatic cancer remains conflicting. We carried out a systematic search of Pubmed and Embase databases for studies published before August 2016, which assessed the associations between anti-diabetic medications (metformin, sulfonylureas, thiazolidinediones and insulin) intake and pancreatic cancer prognosis. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using the random-effects model. The primary outcomes of interest were overall survival (OS) and progression-free survival (PFS). Fourteen studies enrolling 94778 participants were eligible for inclusion, with 12 cohort studies and 2 randomized controlled trials (RCTs). Significant association between metformin (adjusted HR=0.77, 95% CI=0.68-0.87) use and OS was found in cohort studies, whereas no significant association between metformin use and PFS (HR=1.22; 95% CI=0.76-1.95) or OS (HR=1.20, 95% CI=0.84-1.72) in RCTs. No significant survival benefits were identified for insulin (HR=1.18, 95% CI=0.83-1.69), sulfonylureas (HR=1.03, 95% CI=0.81-1.30), or thiazolidinediones (HR=0.84, 95% CI=0.58-1.22). The trim-and-fill method and subgroup analyses stratified by the study characteristics confirmed the robustness of the results. Our findings provide strong evidence that metformin is associated with improved OS in pancreatic cancer patients in cohort studies. However, the effect of other anti-diabetic medications should be interpreted with caution owing to the limited number of studies.