An ethnobotanical study on wild plants used by Tibetan people in Gyirong Valley, Tibet, China.

BACKGROUND: Gyirong Valley known as the "Back Garden of the Himalayas" is located in the core area of the Everest National Nature Reserve. It is also one of the important ports from ancient Tibet to Kathmandu, Nepal, since ancient times. Over the years, the Tibetans of Gyirong had accumulated sufficient traditional knowledge about local plant resources. However, there is almost no comprehensive report available on ethnobotanical knowledge about the local people. The purposes of this study were to (1) conduct a comprehensive study of wild plants used by Tibetan people in Gyirong Valley and record the traditional knowledge associated with wild useful plants, (2) explore the influence of Tibetan traditional culture and economic development on the use of wild plants by local people, and (3) explore the characteristics of traditional knowledge about wild plants of Tibetans in Gyirong. METHODS: Ethnobotanical data were documented through free listings, key informant interviews and semi-structured interviews during fieldwork. The culture importance index and the informant consensus factor index were used as quantitative indices. RESULTS: In total, 120 informants (61 women and 59 men) and 3333 use reports and 111 wild plant species belonging to 39 families and 81 genera were included. These use reports were then classified into 27 categories belonging to three major categories. The use category that contained the most plant species was edible plants (62), followed by medicinal plants (32) and economic plants (22), and other uses (71). Plants with high CI included Allium prattii, Neopicrorhiza scrophulariiflora, Gymnadenia orchidis, Rhododendron anthopogon and Fritillaria cirrhosa. Thirty-six species of plants in the catalog of Gyirong and Yadong were the same, but only 17 species were the same in Gyirong and Burang. There were only 11 overlapping species between all the three regions. CONCLUSION: Tibetans of Gyirong have rich and unique knowledge about plant use, and wild edible and medicinal plants play an important role in the nutrition and health protection of local people. However, traditional knowledge is slowly being lost and is being hit by modern tourism. In the future, more attention needs to be paid to the important role of traditional knowledge in biodiversity conservation.

First-line pembrolizumab plus chemotherapy for extensive-stage small-cell lung cancer: a United States-based cost-effectiveness analysis.

BACKGROUND: The clinical trial of Keynote-604 showed that pembrolizumab plus chemotherapy could generate clinical benefits for extensive-stage small-cell lung cancer (ES-SCLC). We aim to assess the efficacy and cost of pembrolizumab combined with chemotherapy in the first-line treatment setting of ES-SCLC from the United States (US) payers' perspective. METHODS: A synthetical Markov model was used to evaluate cost and effectiveness of pembrolizumab plus platinum-etoposide(EP) versus EP in first-line therapy for ES-SCLC from the data of Keynote-604. Lifetime costs life-years(LYs), quality adjusted LYs(QALYs) and incremental cost-effectiveness ratios(ICERs) were estimated. One-way and probabilistic sensitivity analyses were performed. Furthermore, we performed subgroup analysis. RESULTS: Pembrolizumab plus EP resulted in additional 0.18 QALYs(0.32 LYs) and corresponding incremental costs $113,625, resulting an ICER of $647,509 per QALY versus EP. The price of pembrolizumab had a significant impact on ICER. Probabilistic sensitivity analysis indicated that pembrolizumab combined chemotherapy may become a cost-effective option with a probability of 0%. Besides, subgroup analysis suggested that all subgroups were not cost-effective. CONCLUSION: From the perspective of the US payer, pembrolizumab plus EP is not a cost-effective option for first-line treatment patients with ES-SCLC at a WTP threshold of $150,000 per QALY.

Cost-Effectiveness Analysis of Durvalumab Plus Chemotherapy in the First-Line Treatment of Extensive-Stage Small Cell Lung Cancer.

BACKGROUND: In the CASPIAN trial, durvalumab + chemotherapy demonstrated significant improvements in overall survival compared with chemotherapy alone in patients with extensive-stage small cell lung cancer (SCLC). We aimed to assess the cost-effectiveness of durvalumab in patients with extensive-stage SCLC from the US healthcare system perspective. PATIENTS AND METHODS: A comprehensive Markov model was adapted to evaluate cost and effectiveness of durvalumab combination versus platinum/etoposide alone in the first-line therapy of extensive-stage SCLC based on data from the CASPIAN study. The main endpoints included total costs, life years (LYs), quality-adjusted life-years (QALYs), and incremental cost-e-ectiveness ratios (ICERs). Model robustness was assessed with sensitivity analysis, and additional subgroup analyses were also performed. RESULTS: Durvalumab + chemotherapy therapy resulted in an additional 0.27 LYs and 0.20 QALYs, resulting in an ICER of $464,711.90 per QALY versus the chemotherapy treatment. The cost of durvalumab has the greatest influence on this model. Subgroup analyses showed that the ICER remained higher than $150,000/QALY (the willingness-to-pay threshold in the United States) across all patient subgroups. CONCLUSIONS: Durvalumab in combination with platinum/etoposide is not a cost-effective option in the first-line treatment of patients with extensive-stage SCLC.

Systematic assessment of structure-promiscuity relationships between different types of kinase inhibitors.

Given the increasing quest for selective kinase inhibitors, we have systematically investigated structural and structure-promiscuity relationships between promiscuous kinase inhibitors and other types with increasing potential for selective kinase inhibition. Therefore, inhibitors with different modes of action were extracted from X-ray structures of kinase complexes. For more than 18,000 promiscuous kinase inhibitors and 1253 type I1/2, II, and allosteric inhibitors with structurally confirmed mechanisms, analogue space was systematically charted. These inhibitors were active against a total of 426 human kinases. While nearly 80% of the promiscuous inhibitors formed related analogues series, only ~30% of other types of inhibitors were involved in such structural relationships and many of these inhibitors also had multi-kinase activity. Thus, most of the investigated type I1/2, II, and allosteric inhibitors with reported single-kinase activity were distinguished from promiscuous inhibitors, thus indicating potential for kinase selectivity. Structural relationships between promiscuous inhibitors and the subset of other inhibitors were organized in a matrix format including kinase activity profiles, revealing structure-promiscuity relationships for follow-up investigations.

Cost-Effectiveness Analysis of Encorafenib, Binimetinib, and Cetuximab in BRAF V600E-Mutated Metastatic Colorectal Cancer in the USA.

INTRODUCTION: Recently the phase 3 BEACON trial showed that the combination of encorafenib, cetuximab, and binimetinib versus cetuximab and irinotecan/FOLFIRI improved overall survival in pre-treated patients with metastatic colorectal cancer (mCRC) with BRAF V600E mutation. However, whether the benefits of these therapies justify their high costs has not been estimated in the USA. The purpose of this study was to evaluate the cost-effectiveness of BEC (binimetinib, encorafenib, and cetuximab), EC (encorafenib and cetuximab), and CI/CF (cetuximab with irinotecan or FOLFIRI) in patients with BRAF V600E-mutated mCRC after first- and second-line therapy. METHODS: A Markov model was constructed to determine the costs and effects of BEC, EC, and CI/CF on the basis of BEACON trial outcomes data. Health outcomes were measured in life years (LYs), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). Deterministic and probabilistic sensitivity analyses characterized parameters influencing cost-effectiveness. Subgroup analyses were conducted as well. RESULTS: The QALYs gained in BEC, EC, and CI/CF were 0.62, 0.54, and 0.40, respectively. BEC resulted in ICERs of $883,895.73/QALY and $1,646,846.14/QALY versus CI/CF and EC, respectively. Compared with CI/CF, the ICER was $435,449.88/QALY in EC. The most sensitive parameters in the comparison among the three arms were the utilities of progressive disease and progression-free survival. Probabilistic sensitivity analyses showed that the probability of BEC and EC being cost-effective was 0%. In subgroup analyses, the ICER remained above the willingness-to-pay threshold of $150,000 per QALY. CONCLUSION: BEC and EC were not cost-effective regimens for patients with pre-treated mCRC with BRAF V600E mutation.

Cost-Effectiveness of Pembrolizumab plus Axitinib Versus Sunitinib as First-Line Therapy in Advanced Renal Cell Carcinoma in the U.S.

BACKGROUND: The data from the phase III clinical trial KEYNOTE-426 indicated that pembrolizumab plus axitinib compared with sunitinib could generate clinical benefits in patients with previously untreated advanced renal cell carcinoma (RCC). Given the incremental clinical benefits, we examined the potential cost-effectiveness of pembrolizumab plus axitinib versus sunitinib in the first-line setting for patients with advanced RCC from the U.S. payers' perspective. MATERIALS AND METHODS: Cost and health outcomes were estimated at a willingness-to-pay (WTP) threshold of $100,000 to $150,000 per quality-adjusted life-year (QALY). One-way and probabilistic sensitivity analyses were performed by varying potentially modifiable parameters, and additional subgroup analyses were performed as well. RESULTS: Upon our analyses, the total treatment costs in the pembrolizumab plus axitinib and sunitinib groups were $522,796 and $348,424 and the QALYs gained 2.90 and 1.72, respectively. In the base-case analysis, compared with receiving sunitinib, patients with advanced RCC receiving pembrolizumab plus axitinib gained 1.18 more QALYs at an incremental cost-effectiveness ratio of $148,676/QALY. The results of subgroup analyses demonstrated that pembrolizumab plus axitinib was most cost-effective for patients who had one organ with metastasis. CONCLUSION: First-line treatment with pembrolizumab plus axitinib, compared with sunitinib, is a cost-effective strategy when the value of WTP is from $100,000 to $150,000 per QALY in patients with advanced RCC. For patients with one-organ metastasis and those in International Metastatic Renal Cell Carcinoma Database Consortium poor risk group, first-line treatment with pembrolizumab plus axitinib is more cost-effective than others. IMPLICATIONS FOR PRACTICE: This was the first study to examine the cost-effectiveness of pembrolizumab plus axitinib versus sunitinib in advanced renal cell carcinoma (RCC). This study found that first-line treatment with pembrolizumab plus axitinib is a cost-effective strategy when the value of willingness-to-pay is from $100,000 to $150,000 per quality-adjusted life-year in patients with advanced RCC from the U.S. payers' perspective.

Cost-Effectiveness Analysis of Nivolumab Plus Ipilimumab vs. Chemotherapy as First-Line Therapy in Advanced Non-Small Cell Lung Cancer.

Background: The CheckMate 227 trial has indicated that nivolumab plus ipilimumab compared with chemotherapy significantly increases long-term survival in the first-line setting of advanced non-small-cell lung cancer (NSCLC). Methods: A Markov model was built to estimate the cost and effectiveness of nivolumab plus ipilimumab vs. chemotherapy as the first-line therapy in patients with advanced NSCLC based on outcomes data from the CheckMate 227 trial. We calculated the cost and health outcomes at a willingness-to-pay (WTP) threshold of $150,000 per quality adjusted life year (QALY) in populations with different programmed death ligand 1 (PD-L1) expression levels (≥50, ≥1, and <1%) or a high tumor mutational burden (TMB) (≥10 mutations per megabase). Sensitivity analysis were used to test the model stability. Results: The outcomes showed that the incremental costs and QALYs by using nivolumab plus ipilimumab were $124180.76 and 1.16, $70951.42 and 0.53, $144093.63 and 0.83 for the advanced NSCLC patients with a PD-L1 expression ≥50%, ≥1%, and <1%, which led to an incremental cost-effective ratio (ICER) of $107403.72, $133732.20, and $172589.15 per QALY, respectively. For patients with a high TMB, nivolumab plus ipilimumab contributed an extra 2.04 QALYs at a cost of $69182.50 per QALY. Conclusion: Nivolumab plus ipilimumab as first-line therapy makes a better cost-effective strategy than chemotherapy in advanced NSCLC patients with PD-L1 expression levels ≥50% and ≥1% or a high TMB, at a willingness-to-pay threshold of $150,000 per QALY, but not in the patients with a PD-L1 expression <1%.

Cost-Effectiveness Analysis of Atezolizumab Plus Chemotherapy in the First-Line Treatment of Metastatic Non-Squamous Non-Small Cell Lung Cancer.

INTRODUCTION: The purpose of this study was to estimate the cost-effectiveness of atezolizumab plus chemotherapy in patients with metastatic non-squamous non-small cell lung cancer (NSCLC) from the United States (US) payers' perspective in the first-line treatment. METHODS: A mathematical Markov model was developed to estimate cost and effectiveness of atezolizumab combination therapy versus carboplatin plus nab-paclitaxel alone in the first-line therapy of metastatic non-squamous NSCLC from the data of IMpower130. Costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) were analyzed, and model robustness was assessed by sensitivity analysis. Additional subgroup analyses were performed as well. RESULTS: Compared to chemotherapy, treatment with atezolizumab plus chemotherapy yields an increase of 0.16 QALYs with an increase in cost of $109,809.13, resulting in an ICER of $670,309.66 per QALY. The most influential factor in this model was the cost of atezolizumab. Probabilistic sensitivity analysis showed that there was 0% probability that atezolizumab plus chemotherapy was cost-effective at willingness-to-pay (WTP) values of $150,000 per QALY. The results of subgroup analyses showed that the ICER remained greater than $150,000/QALY across the all patient subgroups. CONCLUSION: First-line treatment with atezolizumab in combination with carboplatin plus nab-paclitaxel is not a cost-effective option in patients with metastatic non-squamous NSCLC.

Cost-Effectiveness Analysis of First-Line FOLFIRI Combined With Cetuximab or Bevacizumab in Patients With RAS Wild-Type Left-Sided Metastatic Colorectal Cancer.

BACKGROUND: The FIRE-3 phase III clinical trial demonstrated the marked advantage of prolonging the median overall survival of patients with final RAS wild-type (WT) left-sided metastatic colorectal cancer (mCRC) by 38.3 months after treatment with irinotecan, fluorouracil, and leucovorin (FOLFIRI) plus cetuximab and by 28.0 months after treatment with FOLFIRI plus bevacizumab. However, the substantial cost increase and economic impact of using cetuximab imposes a considerable burden on patients and society. METHODS: A Markov model based on the data collected in the FIRE-3 trial was developed to investigate the cost-effectiveness of treating patients with FOLFIRI plus either cetuximab or bevacizumab from the perspective of the Chinese health-care system. Costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated over a lifetime horizon. One-way and probabilistic sensitivity analyses were performed by varying potentially modifiable parameters. RESULTS: In our analysis, the total treatment costs in the bevacizumab and cetuximab groups were $92 549.31 and $94 987.31, respectively, and the QALYs gained were 1.58 and 2.05. In the base-case analysis, compared with bevacizumab, left-sided RAS WT patients receiving cetuximab gained 0.47 more QALYs at an ICER of $5187.23/QALY ($3166.23/LY). The 1-way sensitivity analysis showed that the most influential parameter was the cost of cetuximab. Probabilistic sensitivity analysis indicated that the cost-effective probability of cetuximab group was 92.8% under the willingness-to-pay threshold of $24 081. CONCLUSIONS: Treatment with FOLFIRI plus cetuximab in Chinese patients with left-sided RAS WT mCRC may improve health outcomes and use financial resources more efficiently than FOLFIRI plus bevacizumab.

Cost-effectiveness analysis of pembrolizumab versus chemotherapy as first-line treatment in locally advanced or metastatic non-small cell lung cancer with PD-L1 tumor proportion score 1% or greater.

OBJECTIVE: The purpose of this study was to estimate the cost-effectiveness analysis of pembrolizumab versus chemotherapy as first-line treatment in locally advance or metastatic non-small cell lung cancer (NSCLC) with programmed death ligand 1 (PD-L1) tumor proportion score (TPS) 1% or greater from the United States (US) payer perspective. MATERIALS AND METHODS: This Markov structure was developed to estimate cost and effectiveness of pembrolizumab vs chemotherapy in the first-line treatment of locally advance or metastatic NSCLC based on the data from KEYNOTE-042. Cost and health outcomes were estimated at a willingness-to-pay (WTP) threshold of $150,000 per quality adjusted life year (QALY) in three PD-L1 TPS populations (≥50%, ≥20% and ≥1%). One-way, two-way and probabilistic sensitivity analysis were to test the model stability. Subgroup analysis were performed in three PD-L1 TPS populations (≥50%, ≥20% and ≥1%). RESULTS: The incremental costs and QALYs that pembrolizumab yielded, compared with chemotherapy, were $86164.87 and 0.63, $74562.25 and 0.46 and $70886.65 and 0.39 for the populations with a PD-L1 TPS ≥ 50%, TPS ≥ 20% and TPS ≥ 1%, leading an incremental cost-effective ratio (ICER) of $136,228.82, $160,625.98 and $179,530.17 per QALY, respectively. CONCLUSION: First-line treatment with pembrolizumab is a cost-effective strategy compared with platinum-based chemotherapy when the value of WTP was $150,000 per QALY in locally advanced or metastatic NSCLC patients with PD-L1 TPS ≥ 50% and without epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) mutations, but not in the TPS ≥ 20% and 1% populations.

Cost-effectiveness analysis of utidelone plus capecitabine for metastatic breast cancer in China.

Objective: To estimate the cost-effectiveness of utidelone plus capecitabine therapy compared to capecitabine alone in patients with metastatic breast cancer (MBC) resistant to anthracyclines and taxanes treatment in the Chinese context and provide a reference for the marketing of utidelone in China. Methods: A Markov model was developed based on the NCT02253459 clinical trial to simulate the clinical course of patients with metastatic breast cancer who had received taxanes and anthracycline therapy. The quality-adjusted life years (QALYs) and Incremental Cost Effectiveness Ratio (ICER) were then analyzed to evaluate the benefits. Two-parametric Weibull distribution was conducted to fit PFS and OS curves by using R. Sensitivity analyses were performed to evaluate the stability of the model designed. Results: The addition of utidelone increased the cost and QALYs by $13,370.25 and 0.1961, respectively, resulting in an increased ICER of $68,180.78 per QALY. The most sensitive influential parameter on ICER was the price of utidelone. At the threshold of willingness-to-pay (WTP) of $24,380 (3 per capita GDP of China), the cost of utidelone per 30 mg of less than $18.5, $33.7, and greater than $48.8 resulted in a 100%, 50%, and 0% possibility of cost-effectiveness, respectively. The addition of utidelone was not cost-effective when it was $115.4 per 30 mg-the price of its analog paclitaxel. In consideration of varied economics levels across China, cost-effectiveness could be achieved with the price of utidelone ranging from $5.2 to $35.9. Limitations: The survival curves extended beyond the follow-up time horizon, of which data were generated not from the real analyses but from our established two-parameter Weibull survival model. Conclusion: It is recommended that the price of utidelone would be less than $18.5 per 30 mg in order to obtain cost-effectiveness for metastatic breast cancer patients resistant to anthracyclines and taxanes treatment in China.