A cost analysis of SIR-Spheres yttrium-90 resin microspheres versus tyrosine kinase inhibitors in the treatment of unresectable hepatocellular carcinoma in France,Italy, Spain and the UK

Abstract

Background and aims: A wide range of treatment options are available for hepatocellular carcinoma (HCC), including systemic treatment with tyrosine kinase inhibitors (TKIs) such as sorafenib and lenvatinib, immunotherapies, locoregional therapies such as selective internal radiation therapy (SIRT) and treatments with curative intent such as resection, radiofrequency ablation and liver transplantation. Given the substantial economic burden associated with HCC treatment, the aim of the present analysis was to establish the cost of using SIRT with SIR-Spheres yttrium-90 (Y-90) resin microspheres versus TKIs from healthcare payer perspectives in France, Italy, Spain and the United Kingdom (UK).

Methods: A cost model was developed to capture the costs of initial systemic treatment with sorafenib (95%) or lenvatinib (5%) versus SIRT in patients with HCC in Barcelona Clinic Liver Cancer (BCLC) stages B and C. A nested Markov model was utilized to model transitions between progression-free survival (PFS), progression and death, in addition to transitions between subsequent treatment lines. Cost and resource use data were identified from published sources in each of the four countries.

Results: Relative to TKIs, SIRT with SIR-Spheres Y-90 resin microspheres were found to be cost saving in all four country settings, with the additional costs of the microspheres and the SIRT procedure being more than offset by reductions in drug and drug administration costs, and treatment of adverse events. Across the four country settings, total cost savings with SIR-Spheres Y-90 resin microspheres fell within the range 5.4–24.9% and SIRT resulted in more patients ultimately receiving treatments with curative intent (4.6 vs. 1.4% of eligible patients).

Conclusion: SIR-Spheres Y-90 resin microspheres resulted in cost savings relative to TKIs in the treatment of unresectable HCC in all four country settings, while increasing the proportion of patients who become eligible for treatments with curative intent.     

Cost-effectiveness analysis of ramucirumab treatment for patients with hepatocellular carcinoma who progressed on sorafenib with α-fetoprotein concentrations of at least 400 ng/ml

Abstract

Objective: This study aimed to compare the cost-effectiveness of ramucirumab versus placebo for patients with hepatocellular carcinoma who progressed on sorafenib with α-fetoprotein concentrations (AFP) of at least 400?ng/ml in the United States.

Methods: A Markov model was constructed to assess the cost-effectiveness of ramucirumab. Health outcomes were measured as quality-adjusted life years (QALYs). With TreeAge software, the disease process was modeled as three health states: progression-free survival (PFS), progressive disease (PD), and death. Costs were extracted from the REACH-2 trial, and utility was derived from published literature. Incremental cost-effectiveness ratios (ICERs) were calculated to compare ramucirumab with placebo. Probabilistic sensitivity analyses were developed to examine the robustness of the results.

Results: In the base case analysis, ramucirumab therapy had a cost of $55,508.41 and generated 0.54 QALYs, while placebo therapy had a cost of $761.09 and generated 0.47 QALYs, leading to an additional $54,747.32 in costs and 0.07 QALYs. The ICER was $782,104.57 per QALY, which was much higher than the willingness-to-pay threshold of $100,000 per QALY. According to sensitivity analyses, the utility of PD in the two groups was the dominant parameter influencing the ICER.

Conclusion: Although ramucirumab was associated with prolonged survival for patients with advanced hepatocellular carcinoma who progressed on sorafenib treatment with an AFP of at least 400?ng/ml, it is not a cost-effective treatment from a United States payer perspective.     

人肝癌BEL7404／ADM耐药株的建立及生物学特性的评价

建立人肝癌BEL7404／ADM耐药株,并检测该耐药株的生物学特性。通过盐酸阿霉素（adria-mycin,ADM）长期筛选人肝癌细胞株BEL7404,建立阿霉素耐药株BEL7404／ADM。应用M1T法对该细胞株药物敏感性和倍增时间进行检测,用流式细胞仪对其细胞周期和P-糖蛋白（P—glycoprotein,P—gp）功能进行研究。用浓度梯度递增法对BEL741M细胞连续作用10个月,得到人肝癌BEL7404／ADM耐药株。经检测该耐药株IC50是BEL7404细胞株的68．7倍,倍增时间延长了6．49h,两者细胞周期无明显差异性,P—gP活性高于BEL7404细胞株。成功建立了人肝癌BEL7404／ADM耐药株,该耐药株的生物学特性明显不同于BEL7404细胞株;耐药性与P—gp的高表达有关。     

MDM2和PTEN基因表达与贲门癌发生发展的相关性

目的 MDM2、PTEN基因表达与贲门癌发生发展关系的研究。方法用免疫组化S-P法检测32例贲门癌组织及18例正常贲门粘膜组织中MDM2和PTEN表达情况。结果贲门癌组织中MDM2表达34.4%,显著高于正常贲门粘膜组织(P<0.05),且与贲门癌淋巴结转移、浸润深度呈正相关。PTEN在贲门癌组织中的表达40.6%,显著低于正常贲门粘膜组织(P<0.05),且与贲门癌淋巴结转移、分化程度相关。结论 MDM2和PTEN异常表达与贲门癌的关系密切,共同参与了贲门癌的发展、转移及浸润。     

Hospital economic impact from hemostatic matrix usage in cardiac surgery

Objective:

Improved health outcomes can result in economic savings for hospitals and payers. While effectiveness of topical hemostatic agents in cardiac surgery has been demonstrated, evaluations of their economic benefit are limited. This study quantifies the cost consequences to hospitals, based on clinical outcomes, from using a flowable hemostatic matrix vs non-flowable topical hemostatic agents in cardiac surgery.

Research design and methods:

Applying clinical outcomes from a prospective randomized clinical trial, a cost consequence framework was utilized to model the economic impact of comparator groups. From that study, clinical outcomes were obtained and analyzed for a flowable hemostatic matrix (FLOSEAL, Baxter Healthcare Corporation) vs non-flowable topical hemostats (SURGICEL Nu-Knit, Ethicon–Johnson &; Johnson; GELFOAM, Pfizer). Costing analyses focused on the following outcomes: complications, blood transfusions, surgical revisions, and operating room (OR) time. Cardiac surgery costs were analyzed and expressed in 2012 US dollars based on available literature searches and US data. Comparator group variability in cost consequences (i.e., cost savings) was calculated based on annualized impact and scenario testing.

Results:

Results suggest that if a flowable hemostatic matrix (rather than a non-flowable hemostat) was utilized exclusively in 600 mixed cardiac surgeries annually, a hospital could improve patient outcomes by a reduction of 33 major complications, 76 minor complications, 54 surgical revisions, 194 transfusions, and 242?h of OR time. These outcomes correspond to a net annualized cost consequence savings of $5.38 million, with complication avoidance as the largest contributor.

Conclusions:

This cost consequence framework and supportive modeling was used to evaluate the hospital economic impact of outcomes resulting from the usage of various hemostatic agents. These analyses support that cost savings can be achieved from routine use of a flowable hemostatic matrix, rather than a non-flowable topical hemostat, in cardiac surgery.     

肝动脉化疗栓塞联合微波消融治疗巨块型肝癌疗效观察

目的探讨经肝动脉化疗栓塞术(TACE)联合经皮微波消融治疗(PMCT)巨块型肝癌的临床疗效及应用价值。方法回顾性分析我院经病理、影像学证实的巨块型肝癌70例(病灶>10cm),其中对照组(TACE组)38例仅给予TACE治疗,联合治疗组32例先行TACE治疗2周后再行微波消融治疗。结果 TACE组患者1、2、3年生存率分别为66%、53%和18%,中位生存期18.1个月,联合治疗组患者1、2、3年生存率分别为88%、56%和55%,中位生存期24.0个月,两组生存率比较差异有统计学意义(P<0.05)。结论经肝动脉化疗栓塞术联合微波消融治疗巨块型肝癌疗效好,可成为巨块型肝癌的标准治疗模式之一。     

Overall survival,costs, and healthcare resource use by line of therapy in Medicare patients with newly diagnosed metastatic urothelial carcinoma

Aims: Medicare patients with metastatic or surgically unresectable urothelial carcinoma (mUC) often receive platinum-based chemotherapy as first line of therapy (LOT), but invariably progress, requiring additional LOTs and healthcare resource use (HCRU). To better understand the evolving mUC treatment landscape, the economic burden of chemotherapy-based mUC treatments among US Medicare patients was estimated.

Methods: Newly diagnosed Medicare patients with mUC were identified from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Patients were followed from diagnosis to death, disenrollment, or end of study to characterize LOTs (first [LOT1], second [LOT2], and third or greater [LOT3+]). Kaplan-Meier methods were used to estimate overall survival (OS) by LOT. HCRU and mean costs were reported over the follow-up period, LOT duration, and maximum LOT received.

Results: Among 1,873 eligible patients with mUC (median age?=?77?years; median follow-up?=?7.5?months), 1,035 (55%) received no chemotherapy. Among chemotherapy-treated patients, 61% had LOT1 only, 25% had LOT1 and LOT2 only, and 14% had LOT3+. Median OS was 8.1?months, range was 4.3 (untreated) to 29.8 (LOT3+) months. HCRU frequency increased with additional LOTs. Mean cumulative per-patient cost was $82,912 for all patients, increasing with additional LOTs (untreated?=?$57,207; LOT1?=?$99,213; LOT2?=?$125,190; LOT3+?=?$163,884). Mean per patient per month cost was $18,827 for all patients, decreasing with increasing number of LOTs received (untreated?=?$27,211; LOT1?=?$9,601; LOT2?=?$7,325; LOT3+?=?$6,017).

Limitations: Potential for treatment misclassification when using the algorithm defining LOTs and non-generalizability of results to younger patients.

Conclusions: Over 50% of Medicare patients with mUC received no chemotherapy. Among chemotherapy-treated patients, most received only one LOT. Additional LOTs led to higher mean costs and HCRU, but as patients were followed longer, monthly costs decreased. As treatments evolve to include immuno-oncology agents, these findings provide a clinically relevant economic benchmark for mUC treatment across different traditional LOTs.     

Real-world comparison of all-cause hospitalizations,hospitalizations due to stroke and major bleeding,and costs for non-valvular atrial fibrillation patients prescribed oral anticoagulants in a US health plan

Aims: To compare the risk of all-cause hospitalization and hospitalizations due to stroke/systemic embolism (SE) and major bleeding, as well as associated healthcare costs for non-valvular atrial fibrillation (NVAF) patients initiating apixaban, dabigatran, rivaroxaban, or warfarin.

Materials and methods: NVAF patients initiating apixaban, dabigatran, rivaroxaban, or warfarin were selected from the OptumInsight Research Database from January 1, 2013–September 30, 2015. Propensity score matching (PSM) was performed between apixaban and each oral anticoagulant. Cox models were used to estimate the risk of stroke/SE and major bleeding. Generalized linear and 2-part models were used to compare healthcare costs.

Results: Of the 47,634 eligible patients, 8,328 warfarin-apixaban pairs, 3,557 dabigatran-apixaban pairs, and 8,440 rivaroxaban-apixaban pairs were matched. Compared to apixaban, warfarin patients were associated with a significantly higher risk of all-cause (hazard ratio [HR]?=?1.30; 95% confidence interval [CI]?=?1.21–1.40) as well as stroke/SE-related (HR?=?1.60; 95% CI?=?1.23–2.07) and major bleeding-related (HR?=?1.95; 95% CI?=?1.60–2.39) hospitalization; rivaroxaban patients were associated with a higher risk of all-cause (HR?=?1.15; 95% CI?=?1.07–1.24) and major bleeding-related hospitalization (HR?=?1.71; 95% CI?=?1.39–2.10); and dabigatran patients were associated with a higher risk of major bleeding hospitalization (HR?=?1.46, 95% CI?=?1.02–2.10). Warfarin patients had significantly higher major bleeding-related and total all-cause healthcare costs compared to apixaban patients. Rivaroxaban patients had significantly higher major bleeding-related costs compared to apixaban patients. No significant results were found for the remaining comparisons.

Limitations: No causal relationships can be concluded, and unobserved confounders may exist in this retrospective database analysis.

Conclusions: This study demonstrated a significantly higher risk of hospitalization (all-cause, stroke/SE, and major bleeding) associated with warfarin, a significantly higher risk of major bleeding hospitalization associated with dabigatran or rivaroxaban, and a significantly higher risk of all-cause hospitalization associated with rivaroxaban compared to apixaban. Lower major bleeding-related costs were observed for apixaban patients compared to warfarin and rivaroxaban patients.     

替西罗莫司联合索拉非尼治疗晚期肾癌的效果及对患者血清基质金属蛋白酶-9与金属蛋白酶组织抑制剂-1水平的影响

目的探讨替西罗莫司联合索拉非尼治疗晚期肾癌的效果及对患者血清基质金属蛋白酶-9(MMP-9)、金属蛋白酶组织抑制剂-1(TIMP-1)水平的影响。方法选取2011年3月至2016年6月惠东县人民医院收治的晚期肾癌患者72例作为研究对象,按照入院先后顺序编号,应用随机信封法将所有患者分为对照组与观察组,各36例。对照组患者给予索拉非尼,观察组在对照组治疗基础上辅以替西罗莫司治疗。比较两组患者生命质量、临床疗效、血清MMP-9和TIMP-1水平、不良反应及生存期。结果治疗后,两组患者生命质量各维度评分明显提高,且观察组患者生命质量各维度评分明显高于对照组(P<0.05);观察组患者治疗有效率为30.56%,明显高于对照组11.11%(χ^2=4.126,P=0.042);观察组患者疾病控制率为83.33%,显著高于对照组(χ^2=4.431,P=0.035);治疗后,两组患者血清MMP-9和TIMP-1水平明显降低,且观察组患者血清MMP-9和TIMP-1水平显著低于对照组(P<0.05);治疗期间,两组患者皮疹、腹泻、手足皮肤反应、食欲不振、脱发、恶心呕吐、耳鸣及发热发生率比较,差异无统计学意义(P>0.05);观察组患者3年生存率为41.67%,明显高于对照组的19.44%(χ^2=4.189,P=0.041)。结论替西罗莫司联合索拉非尼治疗晚期肾癌,可有效提高临床疗效,改善患者生命质量,下调血清MMP-9和TIMP-1水平,延长患者生存期,安全性好。     

Real-world dosing and drug costs with everolimus or axitinib as second targeted therapies for advanced renal cell carcinoma: a retrospective chart review in the US

Objective:

To describe dosing patterns and to compare the drug costs per month spent in progression-free survival (PFS) among patients with advanced renal cell carcinoma (aRCC) treated with everolimus or axitinib following a first tyrosine kinase inhibitor (TKI).

Methods:

A medical record retrospective review was conducted among medical oncologists and hematologists/oncologists in the US. Patient eligibility criteria included: (1) age ≥18 years; (2) discontinuation of first TKI (sunitinib, sorafenib, or pazopanib) for medical reasons; (3) initiation of axitinib or everolimus as a second targeted therapy during February 2012–January 2013. Real-world dosing patterns were summarized. Dose-specific drug costs (as of October 2014) were based on wholesale acquisition costs from RED BOOK Online. PFS was compared between everolimus and axitinib using a multivariable Cox proportion hazards model. Everolimus and axitinib drug costs per month of PFS were compared using multivariable gamma regression models.

Results:

A total of 325 patients received everolimus and 127 patients received axitinib as second targeted therapy. Higher proportions of patients treated with axitinib vs everolimus started on a higher than label-recommended starting dose (14% vs 2%) or experienced dose escalation (11% vs 1%) on second targeted therapy. The PFS did not differ significantly between patients receiving everolimus or axitinib (adjusted hazard ratio (HR)?=?1.16; 95% confidence interval [CI]?=?0.73–1.82). After baseline characteristics adjustment, axitinib was associated with 17% ($1830) higher drug costs per month of PFS compared to everolimus ($12,467 vs $10,637; p?<?0.001).

Limitations:

Retrospective observational study design and only drug acquisition costs considered in drug costs estimates.

Conclusions:

Patients with aRCC receiving axitinib as second targeted therapy were more likely to initiate at a higher than label-recommended dose and were more likely to dose escalate than patients receiving everolimus. With similar observed durations of PFS, drug costs were significantly higher—by 17% per month of PFS—with axitinib than with everolimus.