Efficacy and safety of Chinese patent medicines combined with antidepressants for treatment of depression in adults: A multiple-treatment meta-analysis.

BACKGROUND: Combinations of Chinese patent medicines (CPM) with antidepressants (including selective serotonin reuptake inhibitors (SSRI), selective serotonin-norepinephrine reuptake inhibitors (SNRI), tricyclic antidepressants (TCA), and noradrenergic and specific serotonergic antidepressants (NaSSA)) are frequently utilized for treating depression in adults. However, the efficacy and safety of these combination treatments remain to be established. METHODS: Systematic search was conducted in seven electronic databases, regulatory websites and international registers of trials from 1994 to 2023 that included adult patients with depressive disorders who received CPM combined with antidepressants. The Multiple-Treatment Meta-Analysis (MTMA) was conducted using a random effects model with Stata/MP17 and R4.3.5 software. Primary outcomes were total efficacy rate, Hamilton Depression Scale (HAMD) score, and Treatment Emergency Symptom Scale (TESS) score. Secondary outcomes included brain-derived neurotrophic factor (BDNF) levels. RESULTS: A total of 146 randomized controlled trials (13,754 participants: 6929 in intervention and 6825 in control groups) were included. For total effective rate, Multiple-Treatment Meta-Analysis results showed that the overall effect of combined intervention was better compared with antidepressants alone, where Jieyuanshenkeli (JYASKL) presented the optimal option for improving total efficacy (OR = 5.39, 95% CI [2.60, 11.18], SUCRA = 84.50%). In reduding the HAMD, Shuganjieyujiaonang (SGJYJN) was most likely to reduce the HAMD score (SMD = -2.20, 95% CI [-3.06, -1.33], SUCRA = 86.10%), Jieyuanshenkeli (JYASKL),Tianewangbuxindan (TWBXD), Shuyukeli (SYKL), Anshenbuxinwan (ASBXW) combination intervention did not appear to be statistically superior to antidepressants alone. In theTreatment Emergency Symptom Scale (TESS), Wulinjiaonang induced the most significant reduction in TESS score (SMD = -1.98, 95% CI [-3.59, -0.36], SUCRA = 90.40%). Tianmengjiaonang (TMJN) + Antidepressants(AD) (SUCRA = 88.30%) displayed the highest scores in increasing the levels of BDNF, although not statistically significant compared to Antidepressants(AD) alone (SMD = 1.23, 95% CI [0.90, 1.55]). CONCLUSION: Combinations of CPM and antidepressants showed superior efficacy over antidepressants alone. The optimal combinations were determined as Shuganjieyu Jiaonang (SGJYJN)/SSRIs and Jieyuanshenkeli (JYASKL)/SSRIs. In terms of safety, results showed that combination therapy did not show better TESS efficacy than antidepressants alone.Although some of the combination interventions were not superior than antidepressants alone in reducing HAMD scores,our findings provide a potentially significant alternative option for clinical complementary therapy. However, these results require further validation through larger sample sizes, multicenter randomized controlled trials, and real-world data.

Cost-effectiveness of Trastuzumab Deruxtecan for HER2-low Advanced Breast Cancer in the United States.

PURPOSE: Trastuzumab deruxtecan has been shown to be effective for advanced breast cancer with low levels of human epidermal growth factor receptor 2. To optimize the allocation of limited health care resources, this study evaluated the cost-effectiveness of trastuzumab deruxtecan from the US payer perspective. METHODS: A partitioned survival model was developed to project the disease course of advanced breast cancer. Clinical efficacy, treatment utilization, safety, and cost data were gathered from the DESTINY-Breast04 (Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer) trial and the Centers for Medicare & Medicaid Services. Transition probabilities were obtained from the reported survival probabilities per DESTINY-Breast04 group. The incremental cost-effectiveness ratio (ICER), the incremental monetary benefit, and the incremental net health benefit were measured. One-way sensitivity analysis, probabilistic sensitivity analysis, and subgroup analysis were performed to explore the uncertainty of the model. FINDINGS: Trastuzumab deruxtecan had an ICER of $307,751 per quality-adjusted life-year (QALY) gained, with an incremental net health benefit of -0.317 QALY and an incremental monetary benefit of -$63,313 compared with the physician's choice of alternative chemotherapy agents. Subgroup analysis indicated that trastuzumab deruxtecan had an ICER of $383,776 per QALY gained for the hormone receptor-positive subgroup and an ICER of $194,424 per QALY for the hormone receptor-negative subgroup. One-way sensitivity analysis showed that the cost of trastuzumab deruxtecan had the most impact on model outcomes. The cost-effectiveness acceptability curve projected that the probability of trastuzumab deruxtecan being cost-effective was 5% in the overall population, 2% in the hormone receptor-positive subgroup, and 56% in the hormone receptor-negative subgroup at the willingness-to-pay threshold of $200,000 per QALY. IMPLICATIONS: Trastuzumab deruxtecan may be a cost-effective option for hormone receptor-negative patients with advanced breast cancer with low levels of human epidermal growth factor receptor 2.

Comparative efficacy of various CHIs combined with western medicine for non-small cell lung cancer: A bayesian network meta-analysis of randomized controlled trials.

Background: Given the limitations of Western medicine (WM) for the treatment of non-small cell lung cancer (NSCLC) and the wide exploration of Chinese herbal injections (CHIs), systematically evaluate the efficacy of Various CHIs Combined with WM for Non-small Cell Lung Cancer. In this study, we performed a network meta-analysis to evaluate the comparative efficacy of 16 CHIs combined with WM regimens for the treatment of NSCLC. Methods: Literature databases were searched from their inception to November 2021, and all randomized control trials (RCTs) involving NSCLC patients treated with a combination of Chinese and WM were retrieved. Outcomes, including disease control rate, survival quality score, incidence of gastrointestinal adverse reactions, incidence of leukopenia, and incidence of thrombocytopenia, were analyzed using RevMan (5.3), Stata17, and R software. Surface under the cumulative ranking curve (SUCRA) probability values were calculated to rank the treatments examined, and clustering analysis was used to compare the effects of CHIs on different outcomes. Results: A total of 389 studies involving 31,263 patients and 16 CHIs were included. The 16 CHIs were: Aidi injection (ADI), Huachansu injection (HCSI), oil of Ophiopogon injection (OOMI), disodium cantharidinate and vitamin B6 injection (DCI), Shenfu injection (SFI), Shenmai injection (SMI), Shenqi Fuzheng injection (SQFZI), Chansu injection (CSI), Delisheng injection (DLSI), Fufang Kushen injection (FFKSI), Huangqi injection (HQI), Kangai injection (KAI), Kanglaite injection (KLTI), Shengmai injection (SI), Xiangguduotang injection (XGDTI), and Xiaoaiping injection (XAPI). The results of the network meta-analysis showed that, with WM treatment as a co-intervention, CSI was most likely to improve the disease control rate (SUCRA = 80.90%), HQI had the highest probability of being the best option for improving the survival quality score (SUCRA = 82.60%), DCI had the highest probability of reducing the incidence of gastrointestinal adverse reactions (SUCRA = 85.50%), HCSI + WM had the highest probability of reducing the incidence of thrombocytopenia (SUCRA = 91.30%), while SMI had the highest probability of reducing the incidence of leukopenia (SUCRA = 79.10%). Conclusion: CHIs combined with WM is proved to be more effective than WM alone, which may be beneficial to NSCLC patients. SMI + WM and DCI + WM are most likely the optimal CHI to improve disease control rates, survival quality score, and reduce adverse effects. This study has limitations; therefore, higher quality RCTs and real-world evidence are required to support our conclusions.

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.

Clinical Benefit and Cost Effectiveness of Risk-Stratified Gastric Cancer Screening Strategies in China: A Modeling Study.

BACKGROUND AND OBJECTIVE: A new gastric cancer screening scoring system (NGCS) strategy was recommended for the early gastric cancer (GC) screening process in China. The current study aimed to assess the clinical benefits and the cost effectiveness of the NGCS strategy in GC high-risk areas of China from a societal perspective. METHODS: A Markov microsimulation model was developed to evaluate 30 alternative screening strategies with varying initiation age, including the NGCS strategy, the modified NGCS strategy, and the endoscopic screening strategy with various screening intervals. The primary outcomes included GC mortality, number of endoscopies, quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs). Cost estimates were reported in 2021 USD (US$) and both costs and benefits were discounted at 5% annually. Deterministic and probabilistic sensitivity analyses were performed to evaluate model uncertainty. RESULTS: Screening with the NGCS strategy from age 40 years (40-NGCS) reduced the GC incidence by 86.4%, which provided the greatest benefit across strategies. Compared with all strategies, at a willingness-to pay threshold of US$17,922 per QALY, the 40-NGCS strategy was a leading cost-effective strategy, with an ICER of US$15,668 per QALY. Results were robust in univariate and probabilistic sensitivity analyses. The probability of the 40-NGCS strategy being cost effective was 0.863. CONCLUSIONS: The 40-NGCS strategy was an effective and cost-effective strategy to reduce GC incidence and mortality in China. The findings provide important evidence for decision makers to formulate and optimize targeted approaches for GC prevention and control policies in China.

Cost-Effectiveness of Bevacizumab Biosimilar LY01008 Combined With Chemotherapy as First-Line Treatment for Chinese Patients With Advanced or Recurrent Nonsquamous Non-Small Cell Lung Cancer.

Objective: To investigate whether LY01008, a locally developed bevacizumab biosimilar agent, is appropriate for widespread use among Chinese advanced or recurrent nonsquamous non-small cell lung cancer (NSCLC) patients, our current study was designed to evaluate the cost-effectiveness of first-line LY01008 combined with platinum-doublet chemotherapy versus chemotherapy alone from the perspective of the Chinese healthcare system. Material and Methods: This economic evaluation designed a Markov model to compare the healthcare cost and quality-adjusted life-year (QALY) of first-line LY01008 combined with chemotherapy versus first-line chemotherapy. Transition probabilities, including disease progression, survival, and adverse event (AE)-related discontinuation of first-line treatment, were estimated using data from the clinical trials. Costs and health utilities were derived from local databases, hospitals, and published literature. Our base case analysis and scenario analysis focused on the cost-effectiveness of chemotherapy combined with a clinical trial dosage (15 mg/kg every 3-week cycle) and a real-world dosage (7.5 mg/kg every 3-week cycle) of LY01008, respectively. Results: In the base case analysis, first-line LY01008 combined with chemotherapy was associated with an increase of 0.48 QALYs in effectiveness and an increase of CNY 189,988 (US$ 26,240) in healthcare costs compared with first-line chemotherapy, resulting an incremental cost-effectiveness ratio (ICER) of CNY 375,425 (US$ 54,430)/QALY. In the scenario analysis, first-line LY01008 combined with chemotherapy was associated with a mean healthcare cost of CNY 265,060 (US$ 38,429), resulting an ICER of CNY 221,579 (US$ 32,125/QALY) between first-line LY01008 combined with chemotherapy versus first-line chemotherapy. The parameters that determine the cost of LY01008 have the greatest impact on the cost-effectiveness results. Conclusion: From the perspective of the Chinese healthcare system, first-line LY01008 at a real-world dosage combined with chemotherapy is likely to represent a cost-effective strategy compared with first-line chemotherapy alone for Chinese advanced or recurrent nonsquamous NSCLC patients.

Sintilimab Plus Bevacizumab Biosimilar Versus Sorafenib as First-Line Treatment for Unresectable Hepatocellular Carcinoma: A Cost-Effectiveness Analysis.

Objective: The ORIENT-32 clinical trial revealed that sintilimab plus bevacizumab biosimilar significantly improved the median progression-free survival and median overall survival (OS) compared with sorafenib. This analysis evaluated the cost-effectiveness of sintilimab plus bevacizumab biosimilar as a first-line treatment for unresectable hepatocellular carcinoma from the Chinese perspective of healthcare system. Materials and methods: A Markov model with three mutual health states was constructed to evaluate the economic outcome of sintilimab plus bevacizumab biosimilar. The model cycle was 21 days, and the simulation time horizon was a lifetime. The output parameters of the model were the total cost, life-year (LY), quality-adjusted LY (QALY), and incremental cost-effectiveness ratio (ICER). Sensitivity analyses were conducted to assess the robustness of the results. Results: The base-case results found that sintilimab plus bevacizumab biosimilar provided an improvement of 1.27 QALYs and 1.84 LYs compared with sorafenib, and the ICER was $23,352/QALY. The hazard ratio for OS had the greatest influence on the ICER. The probability of sintilimab plus bevacizumab biosimilar was 85% at willingness-to-pay thresholds of $30,552/QALY. Conclusion: The findings of this analysis suggested that sintilimab plus bevacizumab biosimilar was a cost-effective first-line therapy for patients with unresectable hepatocellular carcinoma.

Sequences of biological treatments for patients with moderate-to-severe rheumatoid arthritis in the era of treat-to-target in China: a cost-effectiveness analysis.

BACKGROUND: Biologic disease-modifying antirheumatic drugs (bDMARDs) are recommended to be added in sequentially in the treatment of moderate-to-severe rheumatoid arthritis (RA). All these drugs, however, are substantially more expensive than conventional synthetic DMARDs throughout the world, including in China. The objective of this study is to evaluate the cost-effectiveness of treatment sequences of bDMARDs for patients with moderate-to-severe rheumatoid arthritis from the Chinese healthcare system perspective. METHODS: An individual patient simulation model was used to track the course of patients from first treatment through switches to further lines in a sequence. The comparator treatment sequence commenced with methotrexate, followed by non-biologic therapy. The intervention sequences were assumed to be the combinations of bDMARDs available, followed by non-biologic therapy. Life-years, quality-adjusted life-years (QALYs), and lifetime costs were estimated. Univariable and probabilistic sensitivity analyses and scenario analyses were performed to evaluate the model uncertainty. RESULTS: Compared with the comparator treatment sequence, bDMARDs sequences were associated with more life years, QALYs, and cost. These produced ICERs ranged from $27,441.36/QALY to $40,149.2/QALY, above the willingness-to-pay threshold of $10,378 per QALY. The uncertainty analyses and the scenario analyses confirmed the result of the base case analysis. CONCLUSIONS: From the perspective of the Chinese healthcare system, bDMARDs sequences are estimated not to be cost-effective compared with conventional synthetic disease-modifying antirheumatic drug strategy for patients with moderate-to-severe RA at a WTP threshold of $10,378 per QALY. Price reductions are warranted to make bDMARDs cost-effective and affordable.

Cost-Effectiveness of Ipilimumab Plus Anti-PD-1 Therapy Versus Ipilimumab Alone in Patients With Metastatic Melanoma Resistant to Anti-PD-(L)1 Monotherapy.

OBJECTIVE: The use of ipilimumab plus anti-PD-1 has recently been shown to significantly improve the survival of patients with metastatic melanoma resistant to anti-PD-(L)1 monotherapy. The study assessed the cost-effectiveness of ipilimumab plus anti-PD-1 therapy in this population from the US payer perspective. MATERIALS AND METHODS: A Markov model was created based on a retrospective analysis of patients with metastatic melanoma who were resistant to anti-PD-(L)1. Cost information was obtained from the Centers for Medicare and Medicaid Services and literature-based costs. The utility value was derived from the published literature. The results of the model was the total cost, quality-adjusted life-year (QALY), and incremental cost-effectiveness ratio (ICER). The uncertainty of the model was addressed through sensitivity analysis. In addition, we also conducted subgroup analysis. RESULTS: Ipilimumab plus anti-PD-1 provided an improvement of 1.39 QALYs and 2.48 LYs, at a ICER of $73,163 per QALY. The HR of OS was the variable that had the greatest impact on ICER. Compared to ipilimumab, the probability of ipilimumab plus anti-PD-1 being cost-effective was 94% at the WTP of $150,000/QALY. The results of the subgroup analysis showed that the ICER in the majority of the subgroups was less than $150,000/QALY. CONCLUSIONS: Ipilimumab plus anti-PD-1 was likely to be cost-effective compared to ipilimumab for patients with metastatic melanoma who are resistant to anti-PD-(L)1 at a WTP threshold of 150,000/QALY.

Cost-Effectiveness of Nivolumab Plus Cabozantinib Versus Sunitinib as a First-Line Treatment for Advanced Renal Cell Carcinoma in the United States.

Background: In a recent randomized, phase 3 trial (CheckMate 9ER), nivolumab combined with cabozantinib significantly improved patient outcomes compared with sunitinib. However, the cost-effectiveness of these novel agents for untreated advanced renal cell carcinoma (aRCC) remains unknown. Materials and Methods: We constructed a microsimulation decision-analytic model to measure the healthcare costs and outcomes of nivolumab plus cabozantinib compared with those of sunitinib for patients with aRCC. The transition probability of patients was calculated from CheckMate 9ER using parametric survival modeling. Lifetime direct medical costs, life years (LYs), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) were estimated for nivolumab-plus-cabozantinib treatment compared with sunitinib from a US payer perspective. We conducted one-way and probabilistic sensitivity analyses and a series of scenario analyses to evaluate model uncertainty. Results: Nivolumab plus cabozantinib was associated with an improvement of 0.59 LYs and 0.56 QALYs compared with sunitinib. However, incorporating nivolumab plus cabozantinib into first-line treatment was associated with significantly higher lifetime costs ($483,352.70 vs. $198,320.10), causing the incremental cost-effectiveness ratio for nivolumab plus cabozantinib to be $508,987/QALY. The patients' age of treatment, first-line utility, and cost of nivolumab had the greatest influence on the model. The outcomes were robust when tested in sensitivity and scenario analyses. Conclusion: For aRCC, substituting nivolumab plus cabozantinib in the first-line setting is unlikely to be cost-effective under the current willingness-to-pay threshold ($150,000/QALY). Significant price decreases for nivolumab used in first-line therapy would be needed to drop ICERs to a more diffusely acceptable value.

PD-L1 Test-Based Strategy With Nivolumab as the Second-Line Treatment in Advanced NSCLC： A Cost-Effectiveness Analysis in China.

OBJECTIVE: Our previous economic assessment found that nivolumab was not cost-effective for Chinese patients with advanced non-small cell lung cancer (NSCLC) and without EGFR mutations or ALK translocations, when compared with the standard second-line drug docetaxel. However, a greater survival benefit with nivolumab was observed for patients with 1% or greater tumor programmed death ligand 1 (PD-L1) expression. In view of this, we designed the present analysis to explore whether it is cost-effective to use the PD-L1 test to guide second-line nivolumab treatment in China. MATERIAL AND METHODS: A Markov model was established to project the lifetime costs and quality-adjusted life-years (QALYs) of three second-line treatment strategies: nivolumab and docetaxel (strategies without a PD-L1 test) and PD-L1 test-based strategy. Deterministic and probabilistic sensitivity analyses were performed to examine the robustness of our results. Additional price reduction and willingness-to-pay (WTP) threshold scenario analyses were performed to explore the impact of economic and health policies with Chinese characteristics on our results. RESULTS: The PD-L1 test-based strategy costs approximately CNY 194,607 (USD 28,210) or more and yielded an additional 0.27 QALYs compared to the docetaxel strategy without a PD-L1 test, equating an incremental cost-effectiveness ratio (ICER) of CNY 731,089 (USD 105,978)/QALY. Deterministic sensitivity analyses showed that the price of nivolumab was the strongest source of variation in the ICERs. Probability sensitivity analysis showed that the probability for the PD-L1 test-based strategy being cost-effective increases with the increase of WTP thresholds. CONCLUSION: From the perspective of the Chinese healthcare system, using a PD-L1 test to guide second-line nivolumab treatment was not cost-effective. The National Healthcare Security Administration negotiation on the price reduction of nivolumab was found to be the most effective action to improve its cost-effectiveness in China.

Cost-effectiveness analysis of pembrolizumab plus chemotherapy as first-line therapy for extensive-stage small-cell lung cancer.

BACKGROUND: The phase III KEYNOTE-604 study confirmed the benefit of pembrolizumab combined with chemotherapy in the first-line treatment of extensive-stage small-cell lung cancer (ES-SCLC). Taken into account the clinical benefits of pembrolizumab and its high cost, this study aimed to assess the cost-effectiveness of adding pembrolizumab to standard first-line etoposide-platinum (EP) for patients with ES-SCLC from the US payer perspective. METHODS: A Markov model was developed to compare the cost and quality-adjusted life-year (QALY) of pembrolizumab plus EP and placebo plus EP over a 10-year time horizon. Clinical efficacy and safety data were pooled from the KEYNOTE-604 trial. Utilities were obtained from published resources. Costs were mainly collected from Medicare in 2020. Sensitivity analyses were performed to examine the robustness of our model. RESULTS: Adding pembrolizumab to standard first-line EP resulted in the better effectiveness than EP chemotherapy alone for ES-SCLC by 0.22 QALYs. Pembrolizumab plus EP was dominated economically by placebo plus EP, leading to an incremental cost-effectiveness ratio (ICER) of $334,373/ QALY. Deterministic sensitivity analyses indicated that the uncertainty in model parameters exerted no substantial effect on our results. Probability sensitivity analysis indicated that probabilities for pembrolizumab plus EP being cost-effective within a wide range of willingness to pay were modest. CONCLUSION: From the US payer perspective, the first-line treatment for ES-SCLC with pembrolizumab plus EP was not cost-effective compared with placebo plus EP. Although pembrolizumab combination chemotherapy was beneficial to the survival of ES-SCLC, price reduction may be the necessary to improve its cost-effectiveness.

Cost-Effectiveness of Avelumab Maintenance Therapy for Advanced or Metastatic Urothelial Carcinoma in the United States.

INTRODUCTION: The JAVELIN Bladder 100 trial showed that maintenance avelumab therapy after chemotherapy improved the survival of patients with advanced or metastatic urothelial carcinoma. We analyzed the cost-effectiveness of maintenance therapy with avelumab plus best supportive care (BSC) in patients with advanced or metastatic urothelial carcinoma after receiving first-line platinum-based chemotherapy from the US payer perspective. METHODS: A Markov model was used to analyze the economic outcomes of maintenance avelumab plus BSC (avelumab strategy) in the treatment of urothelial carcinoma. The clinical data were derived from the JAVELIN Bladder 100 trial. All cost information was obtained from Medicare and published literature. The total cost, total life years (LYs), total quality-adjusted LYs (QALYs), incremental cost-effectiveness ratio (ICER), and incremental net health benefit (INHB) were calculated. One-way sensitivity analysis and probabilistic sensitivity analysis were also performed. RESULTS: Our results showed that avelumab strategy versus BSC strategy cost US $176,352 and $238,661 and yielded an additional 0.465 and 1.007 QALY in all patients with unknown programmed-death ligand 1 (PD-L1) status and the PD-L1-positive subpopulation, respectively, which led to an ICER of $102,365/QALY and $106,253/QALY gained. In all patients with unknown PD-L1 status, maintenance avelumab plus BSC therapy guiding by PD-L1 expression testing (PD-L1-guided strategy) compared with the avelumab strategy and BSC strategy resulted in ICER of $105,360/QALY and $122,653/QALY, respectively. The probabilities of the avelumab strategy and the PD-L1-guided strategy being cost-effective in the simultaneous competition of the three strategies were 38.49% and 48.82%. In patients with PD-L1-positive status, the avelumab strategy had an 87.51% probability of cost-effectiveness. The most influential parameter for the model was the cost of avelumab and pembrolizumab. CONCLUSIONS: This analysis demonstrated that maintenance therapy with avelumab plus BSC may be a cost-effective option for patients with advanced or metastatic urothelial carcinoma at a willingness-to-pay (WTP) threshold of $150,000/QALY, especially for patients with PD-L1-positive status.

Cost-Effectiveness of Frontline Treatment for Advanced Renal Cell Carcinoma in the Era of Immunotherapies.

Background: Recent randomized controlled trials have demonstrated that immune checkpoint inhibitors (ICIs) improve patient outcomes, but whether these novel agents are cost-effective for untreated advanced renal cell carcinoma (aRCC) remains unclear. Materials and Methods: A microsimulation model was created to project the healthcare costs and outcomes of six strategies (lenvatinib-plus-pembrolizumab, nivolumab-plus-cabozantinib, nivolumab-plus-ipilimumab, pembrolizumab-plus-axitinib, avelumab-plus-axitinib, and sunitinib monotherapy) for patients with aRCC. Transition probability of patients was estimated from CLEAR, CheckMate 9ER, CheckMate 214, KEYNOTE-426, JAVELIN Renal 101, and other data sets by using parametric survival modeling. Lifetime direct medical costs, life years (LYs), quality-adjusted LYs (QALYs), and incremental cost-effectiveness ratios (ICERs) were estimated from a United States payer perspective. One-way and probabilistic sensitivity analyses were performed, along with multiple scenario analyses, to evaluate model uncertainty. Results: Of the six competing strategies, nivolumab-plus-cabozantinib yielded the most significant health outcomes, and the sunitinib strategy was the least expensive option. The cost-effective frontier consisted of the nivolumab-plus-cabozantinib, pembrolizumab-plus-axitinib, and sunitinib strategies, which displayed the ordered ICERs of $81282/QALY for pembrolizumab-plus-axitinib vs sunitinib and $453391/QALY for nivolumab-plus-cabozantinib vs pembrolizumab-plus-axitinib. The rest of the strategies, such as lenvatinib-plus-pembrolizumab, nivolumab-plus-ipilimumab, and avelumab-plus-axitinib, were dominated. The cost of sunitinib drove the model most influentially. Conclusions: For aRCC, the pembrolizumab-plus-axitinib strategy is likely to be the most cost-effective alternative at the willingness-to-pay threshold of $100,000.

Cost-Effectiveness Analysis of Nivolumab Plus Ipilimumab for Advanced Non-Small-Cell Lung Cancer.

Objective: This study evaluated the cost-effectiveness of nivolumab plus ipilimumab vs. chemotherapy in the first-line setting for patients with advanced non-small-cell lung cancer (NSCLC) from the US payer perspective. Materials and methods: A Markov model wasdeveloped to evaluate the cost and effectiveness of nivolumab plus ipilimumab vs. chemotherapy in the first-line treatment of advanced NSCLC. The survival benefits of nivolumab plus ipilimumab were based on the results of the CheckMate 227 trial. The main endpoints of the model were cost, life-years (LYs), quality-adjusted LYs (QALYs), and incremental cost-effectiveness ratio (ICER). Univariable and probabilistic sensitivity analyses were conducted to assess model uncertainty. Additonal subgroup analyses were also performed. Results: nivolumab plus ipilimumab produced a gain of 0.62 QALYs, at a cost of $104238 per QALY. The variables that had the greatest influence on the ICER were body weight and overall survival (OS) hazard ratio (HR). The probability of nivolumab plus ipilimumab being cost-effectiveness compared to chemotherapy is 50.7 and 66.2% when the willingness-to-pay (WTP) value is $ 100,000 and $ 150,000 per QALY. The results of subgroup analyses showed the ICER remained below $150,000/QALY regardless of the PD-L1 expression level. Conclusions: nivolumab plus ipilimumab was estimated to be cost-effective compared with chemotherapy for patients with advanced NSCLC at a WTP threshold from 100,000/QALY to 150,000/QALY.

Cost-Effectiveness Analysis of Cemiplimab Versus Chemotherapy as First-Line Treatment in Advanced NSCLC with PD-L1 Expression Levels of at Least 50.

INTRODUCTION: Cemiplimab may significantly increase overall survival in the first-line treatment of advanced non-small cell lung cancer (NSCLC) with a PD-L1 level of at least 50%. Therefore, there is a need to consider the cost-effectiveness of using this therapy for this indication. METHODS: This Markov model was built to estimate the cost and effectiveness of cemiplimab vs. chemotherapy in the first-line treatment of advanced NSCLC based on the data from the EMPOWER-Lung 1 trial. Life-years (LYs), quality-adjusted LYs (QALYs) and lifetime costs were estimated. One-way and probabilistic sensitivity analyses were performed to evaluate the model uncertainty. Additional subgroup analyses were performed. RESULTS: Treatment of advanced NSCLC with cemiplimab added 0.546 QALYs (1.492 LYs) and resulted in an incremental cost of $22,069.804 compared with chemotherapy, which was associated with an incremental cost-effectiveness ratio of $40,390.412 per QALY gained. The results of one-way sensitivity analysis found that the cost of cemiplimab was the most sensitive factor in our study. The probabilistic sensitivity analysis showed that the probability of cemiplimab being cost-effective was 100%. The subgroup analysis demonstrated that high PD-L1 expression (≥ 90%, > 60 to < 90% and ≥ 50 to ≤ 60%) also kept the incremental cost-effectiveness stable at $63,415.2450 per QALY, $61,896.446 per QALY and $-71,921.259 per QALY. CONCLUSION: From the perspective of US payers, cemiplimab is cost-effective in the first-line treatment of advanced NSCLC at the willingness-to-pay threshold of $150,000 per QALY.

First-line Daratumumab in Addition to Chemotherapy for Newly Diagnosed Multiple Myeloma Patients Who are Transplant Ineligible: A Cost-Effectiveness Analysis.

PURPOSE: Daratumumab is a standard-of-care treatment for newly diagnosed multiple myeloma (NDMM). According to the ALCYONE trial, the addition of daratumumab to bortezomib, melphalan, and prednisone (D-VMP) provides significantly longer overall survival and progression-free survival than bortezomib, melphalan, and prednisone (VMP) in patients with NDMM. However, considering the high price of daratumumab, it is necessary to conduct further research on its efficacy and cost. This study evaluated the cost-effectiveness, from the US payer perspective, of D-VMP vs VMP in the first-line setting for patients with NDMM who are not eligible for autologous stem cell transplantation. METHODS: A Markov model was developed to estimate the lifetime cost and effectiveness of VMP with or without daratumumab as the first-line therapy for patients with NDMM. Univariable sensitivity analysis and probabilistic sensitivity analysis were performed to address the model robustness and uncertainty. Expected value of perfect information analysis was conducted to explore the uncertainty of decision-making and future costs. FINDINGS: D-VMP provides an additional 2.417 quality-adjusted life years (QALYs), at a cost of $30,893 per QALY. Sensitivity analysis revealed that the transition probability of progression-free survival in D-VMP strategy, the price of daratumumab, and body weight of the patient influenced the model results most strongly. Probabilistic sensitivity analysis showed that D-VMP versus VMP has a 90.8% probability of being cost-effective at the $150,000/QALY willingness-to-pay (WTP) threshold. The population expected value of perfect information was $2150 million at a WTP threshold of $50,000/QALY and $1481 million at $100,000/QALY. IMPLICATIONS: In this study, D-VMP was estimated to be cost-effective compared with VMP for patients with NDMM at a WTP threshold of $150,000/QALY.

Cost-Effectiveness of Nivolumab Plus Ipilimumab Combined with Two Cycles of Chemotherapy as First-Line Treatment in Advanced Non-Small Cell Lung Cancer.

INTRODUCTION: The effectiveness of nivolumab plus ipilimumab with two cycles of chemotherapy (NIC) for advanced non-small cell lung cancer (NSCLC) has been demonstrated. We aimed to evaluate the cost-effectiveness of NIC for advanced NSCLC from the US payer perspective. METHODS: A Markov model has been established to predict the disease course of previously untreated advanced NSCLC. The clinical data were derived from the CheckMate 9LA trial. Cost and utility were obtained from the literature. Model outputs included the incremental cost-effectiveness ratios (ICERs), incremental monetary benefit (INMB), and incremental net-health benefit (INHB). A series of sensitivity analyses were performed to analyze the uncertainty of the model. RESULTS: Our results showed that NIC versus chemotherapy alone cost $264,278 and yielded an additional 0.80 quality-adjusted life-years (QALYs), which led to an ICER of $202,275/QALY gained. The INHB was - 0.28 QALY, and the INMB was - $41,865 at the threshold of $150,000/QALY. The results of one-way sensitivity analysis showed that the hazard ratio of overall survival was the most sensitive parameter. CONCLUSION: NIC was unlikely to be cost-effective as a first-line treatment for patients with advanced NSCLC.

Cost-Effectiveness of Lorlatinib as a First-Line Therapy for Untreated Advanced Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer.

INTRODUCTION: Recently, a phase III CROWN trial compared the efficacy of two anaplastic lymphoma kinase (ALK) inhibitors and demonstrated that lorlatinib displayed clinical improvement over crizotinib for advanced non-small cell lung cancer (NSCLC) patients. Therefore, the aim of this study was to estimate the cost-effectiveness of lorlatinib as a first-line therapy for patients with advanced ALK-positive (+) NSCLC. MATERIALS AND METHODS: A cost-effectiveness analysis was performed using a microsimulation model from the US payer perspective and a lifetime horizon (30 years) in patients with previous untreated advanced ALK+ NSCLC. Based on the CROWN trial, patient characteristics were obtained, and the transition probabilities were estimated. All direct costs were derived from official sources and published literature. The main outcomes of the model were total costs, incremental cost-effectiveness ratio (ICER), quality-adjusted life years (QALYs), and life years (LYs). One-way and probabilistic sensitivity analyses and multiple scenario analyses were conducted to test the robustness of the model outcomes. RESULTS: In the base case analysis, in which 1 million patients were simulated, treatment with lorlatinib or crizotinib as the first-line treatment was related to a mean cost of $909,758 and $616,230 (incremental cost: $293,528) and a mean survival of 4.81 QALYs and 4.09 QALYs (incremental QALY: 0.72) per patient, respectively. The main drivers of cost effectiveness were drug price and subsequent cost. PAS indicated that lorlatinib has 90% cost-effectiveness when compared to crizotinib when the willingness-to-pay (WTP) threshold in increased to $448,000/QALY. Scenario analysis demonstrated that lorlatinib has 100% cost-effectiveness at a WTP threshold of 200,000/QALY compared to crizotinib treatment when the price of lorlatinib is decreased to 75% ($424.5) of its original price. CONCLUSIONS: In this study, lorlatinib was unlikely to be cost effective compared with crizotinib for patients with previously untreated advanced ALK+ NSCLC at a WTP threshold of 200,000/QALY.

First-Line Atezolizumab for Metastatic NSCLC with High PD-L1 Expression: A United States-Based Cost-Effectiveness Analysis.

INTRODUCTION: The IMpower110 trial evaluated the efficacy and safety of atezolizumab in previously untreated patients with metastatic non-small cell lung cancer (NSCLC). Due to the high cost of immunity inhibitors, it is necessary to evaluate their value based on their efficacy and cost. This study evaluated the cost-effectiveness of atezolizumab as the first-line treatment for NSCLC with high programmed cell death ligand 1 (PD-L1) expression from the US payer perspective. METHODS: A Markov model with three health states was developed to estimate the cost and outcome of atezolizumab versus platinum-based chemotherapy in patients with previously untreated metastatic NSCLC with high PD-L1 expression. Model outputs included the life-years (LYs), quality-adjusted LYs (QALYs), total cost, and incremental cost-effectiveness ratios (ICERs). One-way and probabilistic sensitivity analyses were performed for all parameters. RESULTS: Atezolizumab produced an additional 1.32 QALYs (2.08 LYs) compared with platinum-based chemotherapy. The accompanying incremental cost was US$224,590. The results of one-way sensitivity analysis found that the ICER was most sensitive to the HR of OS. The probabilistic sensitivity analysis showed that the probability of atezolizumab being cost-effective compared with platinum-based chemotherapy was 10.28% and 37.71% at the willing-to-pay (WTP) threshold of $100,000/QALY and $150,000/QALY, respectively. CONCLUSION: Atezolizumab was estimated not to be cost-effective compared with platinum-based chemotherapy in the first-line treatment of patients with NSCLC with high PD-L1 expression.