Application of Bayesian Approach to Cost-Effectiveness Analysis of Antiviral Treatments in Chronic Hepatitis B.

BACKGROUND: Hepatitis B virus (HBV) infection is a major problem for public health; timely antiviral treatment can significantly prevent the progression of liver damage from HBV by slowing down or stopping the virus from reproducing. In the study we applied Bayesian approach to cost-effectiveness analysis, using Markov Chain Monte Carlo (MCMC) simulation methods for the relevant evidence input into the model to evaluate cost-effectiveness of entecavir (ETV) and lamivudine (LVD) therapy for chronic hepatitis B (CHB) in Jiangsu, China, thus providing information to the public health system in the CHB therapy. METHODS: Eight-stage Markov model was developed, a hypothetical cohort of 35-year-old HBeAg-positive patients with CHB was entered into the model. Treatment regimens were LVD100mg daily and ETV 0.5 mg daily. The transition parameters were derived either from systematic reviews of the literature or from previous economic studies. The outcome measures were life-years, quality-adjusted lifeyears (QALYs), and expected costs associated with the treatments and disease progression. For the Bayesian models all the analysis was implemented by using WinBUGS version 1.4. RESULTS: Expected cost, life expectancy, QALYs decreased with age. Cost-effectiveness increased with age. Expected cost of ETV was less than LVD, while life expectancy and QALYs were higher than that of LVD, ETV strategy was more cost-effective. Costs and benefits of the Monte Carlo simulation were very close to the results of exact form among the group, but standard deviation of each group indicated there was a big difference between individual patients. CONCLUSIONS: Compared with lamivudine, entecavir is the more cost-effective option. CHB patients should accept antiviral treatment as soon as possible as the lower age the more cost-effective. Monte Carlo simulation obtained costs and effectiveness distribution, indicate our Markov model is of good robustness.

Cost-effectiveness analysis of tenofovir disoproxil fumarate for treatment of chronic hepatitis B in China.

BACKGROUND: Tenofovir disoproxil fumarate (TDF) is newly available for treatment of chronic hepatitis B patients in China. To date, no study has been conducted to examine the cost-effectiveness of this treatment. The aim of this study was to estimate the cost-effectiveness of TDF versus four oral nucleos(t)ide analogs [lamivudine (LAM), adefovir (ADV), telbivudine (LdT), and entecavir (ETV)] and from a pharmacoeconomic perspective to assess current drug pricing for TDF. METHODS: Based on Chinese healthcare perspectives, a Markov model was applied to simulate the lifetime (40-year time span) costs and quality-adjusted life-years (QALYs) for five different monotherapy strategies. Two kinds of rescue combination strategies (base-case: LAM + ADV then ETV + ADV; alternative: directly using ETV + ADV) were separately considered for treatment of patients refractory to monotherapy. Model parameters (including disease transition, cost, and utility) were obtained from previous Chinese population studies. Both branded and generic drugs were separately analyzed. Study model uncertainties were assessed by one-way and probabilistic sensitivity analyses. Two-way sensitivity analysis was used to explore uncertainties between efficacy and price of TDF. RESULTS: In the base-case analysis, the lowest lifetime cost and the best cost-effectiveness ratio were obtained by ETV, which was considered the reference treatment. LAM, ADV, and LdT treatments had significantly greater costs and lower efficacies. Compared to ETV, TDF was more effective but also more expensive. The incremental cost-effectiveness ratios of TDF versus ETV were much higher than the willing-to-pay threshold of $20,466 US dollars (USD) per QALY gained (3 × gross domestic product per capita of China, 2014). TDF would be the most cost-effective strategy if the annual cost did not exceed $2260 USD and $1600 USD for branded and generic drugs, respectively. CONCLUSIONS: For Chinese chronic hepatitis B patients, ETV is still the most cost-effective strategy over TDF and other nucleos(t)ide analogs, with a threshold of $20,466 USD/QALY gained.

Cost-effectiveness analysis of lamivudine, telbivudine, and entecavir in treatment of chronic hepatitis B with adefovir dipivoxil resistance.

The purpose of this study was to analyze the cost-effectiveness of lamivudine (LMV), telbivudine (LdT), and entecavir (ETV) in treatment of chronic hepatitis B with adefovir dipivoxil (ADV) resistance. Two hundred and fifty-two patients were recruited and screened for resistance to ADV and randomly assigned into three groups: LMV + ADV, LdT + ADV, and ETV + ADV. The ratio of biochemical response, virological response, seroconversion of hepatitis Be antigen (HBeAg)/hepatitis Be antibody (HBeAb), viral breakthrough, and the cost and effectiveness of treatments were analyzed. A comparison of the results of the ratio of biochemical response, virological response and seroconversion of HBeAg/HBeAb, showed no statistical difference between the three groups, with the economic cost of LMV + ADV the lowest, LdT + ADV the middle, and ETV + ADV the highest. The side effects of the three plans are all rare and tolerable. LMV + ADV is the optimal rescue strategy, and LdT + ADV the alternative selection in the economically less developed regions, while ETV + ADV was used in the economically developed regions.

Prospective assessment of pemetrexed or pemetrexed plus platinum in combination with gefitinib or erlotinib in patients with acquired resistance to gefitinib or erlotinib: a phase II exploratory and preliminary study.

PURPOSE: To evaluate the efficacy and safety of alternating gefitinib and erlotinib, tyrosine kinase inhibitors (TKIs) of the epidermal growth factor receptor (EGFR), with chemotherapy in non-small-cell lung cancer (NSCLC) patients with acquired TKI resistance. METHODS: Forty-two patients with lung cancer that responded to TKIs for as least 6 months before developing TKI resistance were enrolled and received sequential pemetrexed or pemetrexed plus platinum followed by gefitinib or erlotinib. Chemotherapy was intravenously administered on day 1, and patients were provided oral EGFR-TKIs between days 6 and 21. The treatment was repeated every 3 weeks for 2 to 4 cycles. At the end of the specified treatment regimen, patients continued to receive EGFR-TKIs for maintenance until disease progression or unacceptable toxicity. The primary end point was the disease control rate. Secondary end points included overall remission rate, median progression-free survival, and survival rate. RESULTS: The disease control rate was 78.6%, the overall remission rate was 23.8%, and survival rate was 73.8%. Progression-free survival was 8 months, and median survival time was 11 months. The treatment protocol was generally well tolerated. Treatment interruption was required in 2 patients. Grade 3/4 hematologic toxicities included neutropenia (23.8%), leukopenia (16.7%), anemia (4.8%), and thrombocytopenia (4.8%). Common grade 3 nonhematologic toxicities included nausea (7.1%), vomiting (9.5%), anorexia (11.9%), rash (7.1%), fatigue (9.5%), infection (16.7%), and oral mucositis (2.4%). No toxicity-related deaths occurred. CONCLUSIONS: For patients with acquired TKI resistance, pemetrexed or pemetrexed plus platinum administration followed by gefitinib or erlotinib was well tolerated and associated with a fair response.

Cost effectiveness of response-guided therapy with peginterferon in the treatment of chronic hepatitis B.

BACKGROUND & AIMS: The high prevalence of chronic hepatitis B in Asian countries produces a substantial economic burden. Peginterferon has immunomodulatory effects and a finite course for treatment of hepatitis B, but also a high cost and side effects. The recent introduction of a 12-week stopping rule (stopping treatment after 12 weeks) has increased its appeal as a first-line treatment for hepatitis B. We aimed to determine the cost effectiveness of the 12-week stopping rule for peginterferon in hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients. METHODS: We used Markov modeling, with data from the Hong Kong population, to compare the cost effectiveness of peginterferon therapy with a 12-week stopping rule vs conventional therapy (48 weeks) and with other antiviral agents. RESULTS: For HBeAg-positive patients, stopping peginterferon therapy after 12 weeks had the lowest cost-effectiveness ratio (CER), of $9501/quality-adjusted life-year (QALY), compared with no treatment, making it the most cost-effective option. Conventional (48-week) peginterferon treatment had a CER of $9664/QALY. For HBeAg-negative patients, entecavir had the lowest CER ($34,310/QALY). Entecavir was more cost effective than either peginterferon strategies (CERs of $37,423/QALY for 12 weeks of peginterferon and $38,474/QALY for 48 weeks of treatment). CONCLUSIONS: The 12-week stopping rule increases the cost effectiveness of peginterferon therapy, and is the most cost-effective treatment for HBeAg-positive patients. The need for long-term antiviral therapy for HBeAg-negative patients makes entecavir the most cost-effective strategy.

Cost effectiveness of first-line pemetrexed plus platinum compared with other regimens in the treatment of patients with nonsquamous non-small cell lung cancer in the US outpatient setting.

This retrospective observational study evaluated cost effectiveness of first-line treatment of advanced nonsquamous non-small cell lung cancer (NSCLC) with pemetrexed/platinum (Pem/Plat) relative to paclitaxel/carboplatin (Pac/Carbo) and paclitaxel/carboplatin/bevacizumab (Pac/Carbo/Bev). Patients initiating first-line treatment from 2006 to 2009 were identified in electronic medical records of 20 US oncology practices. Pem/Plat patients were matched 1:1 on important characteristics with Pac/Carbo and Pac/Carbo/Bev patients and followed for 1 year to assess progression, survival, and costs. Bootstrapping was used to calculate the probability of falling within quadrants of the incremental cost-effectiveness plane. Kaplan-Meier analysis and Cox proportional hazards regression modeling were also performed. Three hundred Pem/Plat patients (mean age, 67.6 years; male, 56.0%; PS 0/1, 71.0%) were matched with 300 patients in the other cohorts. Median PFS was 134 days (Pem/Plat) versus 106 days (Pac/Carbo) (hazard ratio [HR]: 0.67, P < 0.001) and 126 days (Pac/Carbo/Bev) (HR: 0.68, P < 0.001). Median OS was 298 days (Pem/Plat) versus 218 days (Pac/Carbo) (HR: 0.88, P = 0.08) and 271 days (Pac/Carbo/Bev) (HR: 0.93, P = 0.31). Pem/Plat therapy costs were higher versus Pac/Carbo ($21,841 higher PFS; $19,137 higher OS; P ≤ 0.05) and lower versus Pac/Carbo/Bev ($15,160 lower PFS; $19,946 lower OS; P ≤ 0.05). Pem/Plat had a greater probability of higher costs/higher effectiveness versus Pac/Carbo (PFS, 90.1%; OS, 96.3%) and lower costs/higher effectiveness versus Pac/Carbo/Bev (PFS, 69.5%; OS, 85.0%). Pem/Plat had higher cost and effectiveness than Pac/Carbo; depending on a payer's or society's willingness to pay, Pem/Plat may be considered cost effective compared with Pac/Carbo. Pem/Plat yielded greater effectiveness with lower costs than Pac/Carbo/Bev.

Thymidylate synthase expression and outcome of patients receiving pemetrexed for advanced nonsquamous non-small-cell lung cancer in a prospective blinded assessment phase II clinical trial.

INTRODUCTION: In retrospective analyses of patients with nonsquamous non-small-cell lung cancer treated with pemetrexed, low thymidylate synthase (TS) expression is associated with better clinical outcomes. This phase II study explored this association prospectively at the protein and mRNA-expression level. METHODS: Treatment-naive patients with nonsquamous non-small-cell lung cancer (stage IIIB/IV) had four cycles of first-line chemotherapy with pemetrexed/cisplatin. Nonprogressing patients continued on pemetrexed maintenance until progression or maximum tolerability. TS expression (nucleus/cytoplasm/total) was assessed in diagnostic tissue samples by immunohistochemistry (IHC; H-scores), and quantitative reverse-transcriptase polymerase chain reaction. Cox regression was used to assess the association between H-scores and progression-free/overall survival (PFS/OS) distribution estimated by the Kaplan-Meier method. Maximal χ² analysis identified optimal cutpoints between low TS- and high TS-expression groups, yielding maximal associations with PFS/OS. RESULTS: The study enrolled 70 patients; of these 43 (61.4%) started maintenance treatment. In 60 patients with valid H-scores, median (m) PFS was 5.5 (95% confidence interval [CI], 3.9-6.9) months, mOS was 9.6 (95% CI, 7.3-15.7) months. Higher nuclear TS expression was significantly associated with shorter PFS and OS (primary analysis IHC, PFS: p < 0.0001; hazard ratio per 1-unit increase: 1.015; 95%CI, 1.008-1.021). At the optimal cutpoint of nuclear H-score (70), mPFS in the low TS- versus high TS-expression groups was 7.1 (5.7-8.3) versus 2.6 (1.3-4.1) months (p = 0.0015; hazard ratio = 0.28; 95%CI, 0.16-0.52; n = 40/20). Trends were similar for cytoplasm H-scores, quantitative reverse-transcriptase polymerase chain reaction and other clinical endpoints (OS, response, and disease control). CONCLUSIONS: The primary endpoint was met; low TS expression was associated with longer PFS. Further randomized studies are needed to explore nuclear TS IHC expression as a potential biomarker of clinical outcomes for pemetrexed treatment in larger patient cohorts.

[Analysis of drug therapy of lung cancer in Hungary]. / A tüdorák hazai gyógyszeres kezelésének elemzése.

Hungary is a world leader in lung cancer deaths, so it is particularly important that patients could have access to modern treatments. The aim of our analysis was to find how drug treatments are used in Hungary and how they are compatible with international practice. The in-patient and prescription database of the National Health Insurance Fund for three years (2008-2010) was used to study the frequency of certain chemotherapy protocols, the duration of therapies, and the changes in the individual protocols and drugs used for lung cancer treatment (ICD: C33H0-C34) during the reviewed period. We did not differentiate between neoadjuvant and adjuvant treatment and therapy after progression. During the study period 12326 lung cancer patients received first-line chemotherapy, one third of those (n=3791) received second-line, and one third of those (n=1174) third-line treatment. The average treatment duration was between 3 and 4 months. The first-line treatment of NSCLC mainly consisted of platinum treatment in combination with third generation cytotoxic agents. A downward trend of gemcitabine, still the most common combination compound, was observed, in parallel with the increased use of paclitaxel, and as a consequence carboplatin replaced cisplatin. Among new agents the use of pemetrexed and bevacizumab has increased. Pemetrexed appeared mainly in second-line treatment, while erlotinib also in second, but mostly in third line. The first-line treatment of SCLC consisted of a platinum-etoposide combination, and in second-line setting topotecan was the most commonly used drug. According to our results the chemotherapeutic combinations and sequencing are in accordance with international and national recommendations. Further detailed analysis of the available data may help to obtain more accurate picture of the efficacy of lung cancer treatments as well.

Cost-effectiveness of continuation maintenance pemetrexed after cisplatin and pemetrexed chemotherapy for advanced nonsquamous non-small-cell lung cancer: estimates from the perspective of the Chinese health care system.

BACKGROUND: Continuation maintenance treatment with pemetrexed is approved by current clinical guidelines as a category 2A recommendation after induction therapy with cisplatin and pemetrexed chemotherapy (CP strategy) for patients with advanced nonsquamous non-small-cell lung cancer (NSCLC). However, the cost-effectiveness of the treatment remains unclear. OBJECTIVE: We completed a trial-based assessment, from the perspective of the Chinese health care system, of the cost-effectiveness of maintenance pemetrexed treatment after a CP strategy for patients with advanced nonsquamous NSCLC. METHODS: A Markov model was developed to estimate costs and benefits. It was based on a clinical trial that compared continuation maintenance pemetrexed therapy plus best supportive care (BSC) versus placebo plus BSC after a CP strategy for advanced nonsquamous NSCLC. Sensitivity analyses were conducted to assess the stability of the model. RESULTS: The model base case analysis suggested that continuation maintenance pemetrexed therapy after a CP strategy would increase benefits in a 1-, 2-, 5-, or 10-year time horizon, with incremental costs of $183,589.06, $126,353.16, $124,766.68, and $124,793.12 per quality-adjusted life-year gained, respectively. The most sensitive influential variable in the cost-effectiveness analysis was the utility of the progression-free survival state, followed by proportion of patients with postdiscontinuation therapy in both arms, proportion of BSC costs for PFS versus progressed survival state, and cost of pemetrexed. Probabilistic sensitivity analysis indicated that the cost-effective probability of adding continuation maintenance pemetrexed therapy to BSC was zero. One-way and probabilistic sensitivity analyses revealed that the Markov model was robust. CONCLUSIONS: Continuation maintenance of pemetrexed after a CP strategy for patients with advanced nonsquamous NSCLC is not cost-effective based on a recent clinical trial. Decreasing the price or adjusting the dosage of pemetrexed may be a better option for meeting the treatment demands of Chinese patients.

Prospective assessment of continuation of erlotinib or gefitinib in patients with acquired resistance to erlotinib or gefitinib followed by the addition of pemetrexed.

INTRODUCTION: Patients with epidermal growth factor receptor (EGFR) mutation positive non-small-cell lung cancer exhibited marked response to gefitinib or erlotinib. In most cases, however, the patients showed disease progression after EGFR-tyrosine kinase inhibitor (TKI) treatment. We evaluated the efficacy and safety of pemetrexed in combination with EGFR-TKI in patients with disease progression. METHODS: Patients with EGFR-mutant stage IIIB or IV non-small-cell lung cancer that progressed during gefitinib or erlotinib therapy were administered pemetrexed with the continuation of EGFR-TKI treatment. Pemetrexed was administered on day 1 at a dose of 500 mg/m, and EGFR-TKI was sequentially administered on days 2 to 16. This treatment was repeated every 3 weeks until disease progression. The primary endpoint was disease control rate. RESULTS: Twenty-seven patients were enrolled in this study. The median number of treatment cycles was six. Overall response rate was 25.9% (95% confidence interval, 9.4%-42.4%) and disease control rate was 77.8% (95% confidence interval, 62.1%-93.5%). Grade 3/4 hematological toxicities were neutropenia (22.2%), leukopenia (14.8%), and anemia (7.4%). Grade 4 nonhematological toxicities were not observed. Major grade 3 nonhematological toxicities were anorexia (14.8%), infection (14.8%), and fatigue (11.1%). The median progression-free survival was 7.0 months, and median survival time was 11.4 months. No treatment-related deaths occurred. CONCLUSIONS: Pemetrexed in combination with erlotinib or gefitinib after disease progression shows favorable response and acceptable toxicity.

Cost-utility and budget impact analyses of gefitinib in second-line treatment for advanced non-small cell lung cancer from Thai payer perspective.

AIM: To evaluate the cost utility and budget impact of second-line gefitinib for non-small cell lung cancer from a Thai payer perspective. METHODS: A Markov model with three health states (pre-progression, post-progression and death) was constructed to estimate direct medical costs and outcomes comparing four treatment options, i.e., gefitinib, erlotinib, pemetrexed and docetaxel. The model followed patients for 2 years with discount rate of 3% annually. Clinical inputs and patients' characteristics were based on a randomized phase III trial (INTEREST). Costs were based on reference prices published by the Ministry of Public Health, Thailand, and other information related to treatment from expert opinion and presented in 2010. Deterministic and probabilistic sensitivity analyses were performed to determine the impact of model parameters on results. RESULTS: In the base case model, gefitinib and erlotinib yielded equal quality-adjusted life years (QALY) but 0.0140 and 0.0110 more QALY compared with docetaxel and pemetrexed, respectively. Total costs were 188 848 Baht (US$6237) for gefitinib, 196 313 Baht (US$6483) for docetaxel, 249 177 Baht (US$8229) for erlotinib and 275 303 Baht (US$9092) for pemetrexed. Drug acquisition contributed the greatest component. A series of sensitivity analyses demonstrated the robustness to various parameter variations except for docetaxel cost and duration of treatment. The budget impact analyses demonstrate the greater the percentage of substitution of gefitinib for docetaxel (ranging from 10-60%) the greater the cost saving. CONCLUSION: Gefitinib is a dominant cost saving strategy compared with docetaxel for the second-line treatment of advanced NSCLC from the Thai payer perspective.

Cost-effectiveness of maintenance pemetrexed in patients with advanced nonsquamous-cell lung cancer from the perspective of the Swiss health care system.

OBJECTIVES: A recent randomized study showed switch maintenance with pemetrexed after nonpemetrexed-containing first-line chemotherapy in patients with advanced nonsmall-cell lung cancer to prolong overall survival by 2.8 months. We examined the cost-effectiveness of pemetrexed in this indication, from the perspective of the Swiss health care system, and assessed the influence of the costs of best supportive care (BSC) on overall cost-effectiveness. METHODS: A Markov model was constructed based on the pemetrexed maintenance study, and the incremental cost-effectiveness ratio (ICER) of adding pemetrexed until disease progression was calculated as cost per quality-adjusted life-year gained. Uncertainties concerning the costs of BSC on the ICER were addressed. RESULTS: The base case ICER for maintenance therapy with pemetrexed plus BSC compared to BSC alone was €106,202 per quality-adjusted life-year gained. Varying the costs for BSC had a marked effect. Assuming a reduction of the costs for BSC by 25% in the pemetrexed arm resulted in an ICER of €47,531 per quality-adjusted life-year, which is below predefined criteria for cost effectiveness in Switzerland. CONCLUSIONS: Switch maintenance with pemetrexed in patients with advanced nonsquamous-cell lung cancer after standard first-line chemotherapy is not cost-effective. Uncertainties on the resource use and costs for BSC have a large influence on the cost-effectiveness calculation and should be reported in more detail.

Raltitrexed plus cisplatin is cost-effective compared with pemetrexed plus cisplatin in patients with malignant pleural mesothelioma.

INTRODUCTION: The National Institute for Health and Clinical Excellence (NICE) has previously recommended pemetrexed plus cisplatin for the treatment of patients with advanced malignant pleural mesothelioma (MPM) and WHO performance status 0-1. Subsequent to this appraisal, randomised controlled trial (RCT) data for raltitrexed plus cisplatin and comparing chemotherapy to active symptom control (ASC) has become available, allowing a more complete analysis of the comparative efficacy and cost-effectiveness of first-line chemotherapy in MPM. METHODS: An adjusted indirect comparison is used to estimate the relative efficacy of raltitrexed plus cisplatin and pemetrexed plus cisplatin. A cost-effectiveness model is used to assess the lifetime costs and health outcomes associated with these comparators and ASC. Patient level data from the EORTC 08983 trial are used to estimate baseline progression and survival rates. Relative treatment effects are taken from RCTs; cost and utility data from the literature. RESULTS: Raltitrexed plus cisplatin and pemetrexed plus cisplatin were not found to be statistically significantly different with respect to overall response, progression free survival or overall survival. The cost-effectiveness analysis found raltitrexed plus cisplatin to be cost-effective at a cost per quality adjusted life year of £13,454 compared to cisplatin and £27,360 compared to ASC. Pemetrexed plus cisplatin is dominated by raltitrexed plus cisplatin as the raltitrexed combination offers marginally higher quality adjusted life years (QALYs) and life years (LYs) at a substantially lower total cost. CONCLUSION: Raltitrexed plus cisplatin is a cost-effective first-line treatment for MPM. This conclusion was maintained across a number of sensitivity analyses.

Cost effectiveness of personalized therapy for first-line treatment of stage IV and recurrent incurable adenocarcinoma of the lung.

PURPOSE: Patients with epidermal growth factor receptor (EGFR) mutation-positive stage IV adenocarcinoma have improved survival with tyrosine kinase inhibitor (TKI) treatments, but the cost effectiveness of personalized first-line therapy using EGFR mutation testing is unknown. METHODS: We created a decision analytic model comparing the costs and effects of platinum combination chemotherapy with personalized therapy in which patients with EGFR mutation-positive tumors were treated with erlotinib. We used two testing strategies: testing only those with tissue available and performing a repeat biopsy if tissue was not available versus three nontargeted chemotherapy regimens (ie, carboplatin and paclitaxel; carboplatin and pemetrexed; and carboplatin, pemetrexed, and bevacizumab). RESULTS: Compared with a carboplatin plus paclitaxel regimen, targeted therapy based on testing available tissue yielded an incremental cost-effectiveness ratio (ICER) of $110,644 per quality-adjusted life year (QALY), and the rebiopsy strategy yielded an ICER of $122,219 per QALY. Probabilistic sensitivity analysis revealed substantial uncertainty around these point estimates. With a willingness to pay of $100,000 per QALY, the testing strategy was cost effective 58% of the time, and the rebiopsy strategy was cost effective 54% of the time. Personalized therapy with an EGFR TKI was more favorable when the nontargeted chemotherapy regimen was more expensive. Compared with carboplatin, pemetrexed, and bevacizumab, ICERs were $25,547 per QALY for the testing strategy and $44,036 per QALY for the rebiopsy strategy. CONCLUSION: Although specific clinical circumstances should guide therapy, our cost-effectiveness analysis supports the strategy of testing for EGFR mutations in patients with stage IV or recurrent adenocarcinoma of the lung, rebiopsying patients if insufficient tissue is available for testing, and treating patients with EGFR mutations with erlotinib as first-line therapy.

An indirect comparison of the efficacy of bevacizumab plus carboplatin and paclitaxel versus pemetrexed with cisplatin in patients with advanced or recurrent non-squamous adenocarcinoma non-small cell lung cancer.

OBJECTIVE: There are two new treatment options available for the treatment of adenocarcinoma histology non-small cell lung cancer (NSCLC) which offer improved benefit in terms of progression-free (PFS) and overall survival (OS) over chemotherapy. Both bevacizumab and pemetrexed when combined with chemotherapy significantly increase PFS and OS in patients with advanced NSCLC versus chemotherapy alone. The aim of this analysis was to compare the efficacy for patients with non-squamous adenocarcinoma NSCLC treated with bevacizumab, carboplatin and paclitaxel (BCP) to pemetrexed and cisplatin (PC) by using indirect comparison (ITC) methodology. EXPERIMENTAL DESIGN: In the absence of head-to-head trials, ITC was performed on patients with adenocarcinoma histology non-squamous NSCLC to compare the relative benefit of first-line therapies BCP vs. PC by hazard ratios (HR). Subsequently, these HRs were used in a decision-analytic Markov model with a lifelong time horizon to extrapolate the long-term effectiveness of the two treatments. RESULTS: ITC estimated HRs for the primary endpoints in the bevacizumab study E4599 showed that BCP treatment in non-squamous adenocarcinoma NSCLC patients resulted in a BCP HR of 0.82 versus PC. The long-term predictions from the Markov model yielded a mean survival of 1.48 years (95% CI 1.34, 1.62 years) (or 17.7 months) for BCP compared with 1.29 years (95% CI 1.16, 1.42 years) (or 15.4 months) for PC. CONCLUSIONS: Based on our decision analysis, triplet BCP targeted therapy in patients with advanced non-squamous adenocarcinoma NSCLC compared with doublet PC chemotherapy results in improved expected values for overall long-term survival. Therefore, from the efficacy perspective, bevacizumab in combination with platinum-based chemotherapy can be considered as the targeted therapy of choice for patients with advanced non-squamous adenocarcinoma NSCLC.

[Usefulness of 18F-FDG PET-CT in the presurgical assessment of malignant pleural mesothelioma treated with neoadjuvant chemotherapy]. / Utilidad de la PET-TAC 18F-FDG en la valoración prequirúrgica del mesotelioma pleural maligno tras quimioterapia neoadyuvante.

Malignant pleural mesothelioma is a relatively rare, but highly aggressive, tumor, associated to exposure to asbestos, with a life expectancy between 9 and 17 months. Chest pain and dyspnea are the most frequent symptoms. The most commonly used therapy is surgery accompanied by chemotherapy. Preoperative assessment, after chemotherapy, has been done using magnetic resonance imaging and computed tomography (CT). However, these techniques cannot predict early response to therapy, because of the slow structural change of the tumor. The aim of this case report is to review and learn about the growing use of PET-CT imaging with (18)F-FDG in the preoperative staging of malignant pleural mesothelioma and its influence in selecting the most appropriate type of surgery.

Cost-effectiveness of bevacizumab-based therapy versus cisplatin plus pemetrexed for the first-line treatment of advanced non-squamous NSCLC in Korea and Taiwan.

AIMS: The aim of this analysis is to investigate the mean incremental costs and life expectancy associated with two first-line treatments for advanced non-squamous non-small cell lung cancer (NSCLC) in Korea and Taiwan; bevacizumab plus cisplatin and gemcitabine (BevCG) and cisplatin plus pemetrexed (CP). METHODS: A health economic (area under curve) model with three health states was developed to assess health outcomes (life-years gained [LYG]), direct costs, and incremental cost-effectiveness ratio (ICER). Progression-free survival (PFS) and overall survival (OS) were derived from randomized clinical trials and used in an indirect comparison in order to estimate their cost effectiveness. A life-time horizon was used. Costs and outcomes were discounted yearly by 5% in Korea and by 3% in Taiwan. RESULTS: The incremental LYG for the BevCG patients compared with patients treated with CP were 1.10 (13.2 months) in Korea and 1.19 (14.3 months) in Taiwan. The incremental costs were 37,439,968 ($ 33,322) in Korea and NT$ 1,910,615 ($ 64,541) in Taiwan. The incremental cost-effectiveness ratio was 34,064,835 ($ 30,318) in Korea and NT$ 1,607,960 ($ 54,317) in Taiwan. The inputs tested in one-way sensitivity analyses had very little impact on the overall cost effectiveness. CONCLUSION: This analysis shows that BevCG is more costly but is also associated with additional life-years in Korea and Taiwan. The ICER per LYG suggests that BevCG is a cost-effective therapy when compared to CP for patients with advanced NSCLC in Korea and Taiwan.

Cost-effectiveness analysis of bevacizumab versus pemetrexed for advanced non-squamous NSCLC in Italy.

INTRODUCTION: The new targeted agent bevacizumab in combination with cisplatin and gemcitabine (BCG), and a third-generation chemotherapy pemetrexed in combination with cisplatin (PC), are approved as first-line treatment for patients with advanced non-squamous non-small cell lung cancer (NSCLC). METHODS: An indirect comparison between BCG and PC showed that the bevacizumab triplet achieved a favourable hazard ratio in terms of progression-free survival among patients with advanced NSCLC. This analysis aimed to compare the detailed costs and benefits of these treatments for advanced non-squamous NSCLC in Italy. RESULTS: The monthly cost of single-agent bevacizumab, including administration and supportive care costs, and costs for adverse events as a single agent was 4,007 euro/patient less than pemetrexed over the patient's lifetime. BCG also achieved a mean gain of 0.12 life-years compared with PC over this period. The incremental cost-effectiveness ratio of BCG relative to PC was calculated to be 34,919 euro per additional life-year gained suggesting that BCG is cost-effective compared with PC as first-line treatment for advanced NSCLC in Italy. CONCLUSIONS: In conclusion, bevacizumab-based therapy can be considered as a cost-effective option when compared to chemotherapy treatments such as pemetrexed for the treatment for advanced non-squamous NSCLC.

Costs of bevacizumab and pemetrexed for advanced non-squamous NSCLC in Italy and Germany.

The new targeted agent bevacizumab in combination with cisplatin and gemcitabine, and a third-generation chemotherapy pemetrexed in combination with cisplatin, have been approved as first-line treatment for patients with advanced non-squamous non-small cell lung cancer (NSCLC). An indirect comparison between bevacizumab plus cisplatin and gemcitabine and pemetrexed plus cisplatin showed that bevacizumab (plus cisplatin and gemcitabine) achieved a favourable hazard ratio in terms of progression-free survival among patients with advanced NSCLC. This analysis aimed to compare the monthly cost of these treatments for advanced non-squamous NSCLC in Italy and Germany. The comparison used country specific cost data and adopted the payer perspective in Italy and Germany. The monthly cost of bevacizumab, including administration cost, as a single agent was 1,509 euro and 2,564 euro less than pemetrexed in Italy and Germany, respectively. The monthly treatment cost of bevacizumab plus cisplatin and gemcitabine was 1,001 euro and 446 euro less than pemetrexed plus gemcitabine in Italy and Germany, respectively. Results indicate that clinical benefits with bevacizumab plus cisplatin and gemcitabine therapy are achieved at a lower monthly cost than pemetrexed plus gemcitabine doublet therapy. Therefore, from a budget perspective, bevacizumab should be considered as a preferred targeted treatment of choice for advanced non-squamous NSCLC.

Cost-effectiveness of pemetrexed as first-line maintenance therapy for advanced nonsquamous non-small cell lung cancer.

INTRODUCTION: The primary objective was to estimate the cost-effectiveness of maintenance therapy with pemetrexed (Pem) compared with observation, each with best supportive care, in patients with advanced non-small cell lung cancer (NSCLC) who have completed, without progression, at least four cycles of first-line platinum chemotherapy, particularly in those with nonsquamous cell histology. Secondary comparisons included Pem with erlotinib (Erl) or Pem with bevacizumab (Bev). METHODS: A semi-Markov model was developed to compare the 3-year impact of Pem with three other alternatives for maintenance therapy from a United States payer perspective. Data from randomized controlled clinical trials provided clinical inputs. Medicare reimbursement rates were used to determine drug costs. A retrospective claims database analysis was used to obtain estimates of other direct NSCLC-related costs. RESULTS: In the prespecified subset of patients with nonsquamous cell histology only, the incremental cost per life-year gained was $122,371 for Pem to observation and $150,260 for Pem to Erl, and Bev was dominated by Pem. In all patients with advanced NSCLC regardless of histologic subtype, using Pem as maintenance therapy led to an incremental cost per life-year gained of $205,597 compared with observation and $312,341 compared with Erl. CONCLUSIONS: Compared with observation and other agents used and/or reimbursed for maintenance therapy in advanced NSCLC, Pem may be considered cost-effective, particularly in patients with nonsquamous cell histology. This analysis is the first to evaluate the cost-effectiveness of maintenance therapy in advanced NSCLC and emphasizes the importance of histology in identifying the appropriate patient for Pem maintenance therapy.