Dataset Information

Cost-effectiveness analysis of the first-line EGFR-TKIs in patients with non-small cell lung cancer harbouring EGFR mutations.

ABSTRACT:

Objectives

To compare the cost-effectiveness of first-line gefitinib, erlotinib, afatinib, and osimertinib in patients with non-small cell lung cancer (NSCLC) harbouring epidermal growth factor receptor (EGFR) mutations.

Methods

A systematic review and network meta-analysis (NMA) were conducted to compare the relative efficacy of gefitinib, erlotinib, afatinib, and osimertinib in EGFR-mutated NSCLC. To assess the cost-effectiveness of these treatments, a Markov model was developed from Dutch societal perspective. The model was based on the clinical studies included in the NMA. Incremental costs per life-year (LY) and per quality-adjusted life-year (QALY) gained were estimated. Deterministic and probabilistic sensitivity analyses (PSA) were conducted.

Results

Total discounted per patient costs for gefitinib, erlotinib, afatinib, and osimertinib were €65,889, €64,035, €69,418, and €131,997, and mean QALYs were 1.36, 1.39, 1.52, and 2.01 per patient, respectively. Erlotinib dominated gefitinib. Afatinib versus erlotinib yielded incremental costs of €27,058/LY and €41,504/QALY gained. Osimertinib resulted in €91,726/LY and €128,343/QALY gained compared to afatinib. PSA showed that gefitinib, erlotinib, afatinib, and osimertinib had 13%, 19%, 43%, and 26% probability to be cost-effective at a threshold of €80,000/QALY. A price reduction of osimertinib of 30% is required for osimertinib to be cost-effective at a threshold of €80,000/QALY.

Conclusions

Osimertinib has a better effectiveness compared to all other TKIs. However, at a Dutch threshold of €80,000/QALY, osimertinib appears not to be cost-effective.

SUBMITTER: Holleman MS

PROVIDER: S-EPMC7058671 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Publications

Cost-effectiveness analysis of the first-line EGFR-TKIs in patients with non-small cell lung cancer harbouring EGFR mutations.

Holleman Marscha S MS Al Maiwenn J MJ Zaim Remziye R Groen Harry J M HJM Uyl-de Groot Carin A CA

The European journal of health economics : HEPAC : health economics in prevention and care 20190920 1

<h4>Objectives</h4>To compare the cost-effectiveness of first-line gefitinib, erlotinib, afatinib, and osimertinib in patients with non-small cell lung cancer (NSCLC) harbouring epidermal growth factor receptor (EGFR) mutations.<h4>Methods</h4>A systematic review and network meta-analysis (NMA) were conducted to compare the relative efficacy of gefitinib, erlotinib, afatinib, and osimertinib in EGFR-mutated NSCLC. To assess the cost-effectiveness of these treatments, a Markov model was developed ...[more]

PMID: 31541309

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Project description:Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) has been used for the first-line treatment of non-small cell lung cancer (NSCLC) and has shown good clinical effects. However, some patients fail to benefit from this treatment. The aim of this study is to analyze whether or not clinical-selected patients (Asian, adenocarcinoma histology, non-smoking) and EGFR mutation-selected patients benefit from EGFR-TKIs or chemotherapy. Our results could be used as basis to guide clinical therapy.Randomized controlled trials evaluating the efficacy of EGFR-TKIs versus chemotherapy as first-line treatments of NSCLC were obtained from electronic databases, namely, PubMed, Embase, American Society of Clinical Oncology (ASCO), European Society for Medical Oncology, and China Biology Medicine disc. Assessment, data collection, and statistical analysis were performed according to Cochrane Handbook 5.1.0.A total of 14 randomized controlled trials with 5,000 patients were included in this study. Compared with the chemotherapy group, EGFR-TKI therapy group in EGFR mutation-selected NSCLC patients showed a higher response rate (RR=2.31; 95%CI: 1.88-2.84) and more significant improvement in progression free survival (PFS; HR=0.39; 95%CI: 0.30-0.49); by contrast, no significant difference was observed in overall survival (OS; HR=0.99; 95%CI: 0.84-1.16). The response rate of clinical-selected patients treated with EGFR-TKI significantly increased (RR=1.30; 95%CI: 1.15-1.47) compared with that of the patients treated with chemotherapy; PFS (HR=0.93; 95%CI: 0.58-1.49) and OS (HR=0.91; 95%CI: 0.81-1.02) of the two groups did not significantly differ. Likewise, the PFS and the OS of the unselected patients in the EGFR-TKI treatment group and the chemotherapy group did not significantly differ, although the OS of the former was shorter than that of the latter.EGFR mutation-selected patients received more benefits from EGFR-TKI first-line treatment than other treatments. First-line EGFR-TKI treatment was recommended for clinically selected patients who were unsuitable for themotherapy. By comparison, first-line EGFR-TKI treatment was not a suitable choice for unselected patients.

Project description:Importance:The survival of patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) gene mutations has improved substantially in the last decade with the development of targeted tyrosine kinase inhibitors (TKIs). Osimertinib, a third-generation TKI that is approved by the US Food and Drug Administration for the treatment of patients who develop EGFR T790M mutations, has recently shown improved clinical outcomes compared with gefitinib and erlotinib for treatment-naive patients. Objective:The aim of this study was to assess the cost-effectiveness of osimertinib for the first-line treatment of patients with EGFR-mutated NSCLC. Design, Setting, and Participants:For this cost-effectiveness analysis, we extracted individual patient data from the FLAURA randomized clinical trial and used findings of our earlier meta-analysis to develop a decision-analytic model and determine the cost-effectiveness of osimertinib (AZD9291) compared with first- and second-generation EGFR-TKIs over a 10-year time horizon. All direct costs were based on US and Brazilian payer perspectives. Main Outcomes and Measures:The main outcome of this study was the incremental cost-effectiveness ratio (ICER) expressed as cost per quality-adjusted life-year (QALY) gained by using osimertinib compared with first- or second-generation EGFR-TKIs in previously untreated EGFR-mutated NSCLC. Results:In the base case using the data as reported in the FLAURA trial, the incremental QALY for osimertinib was 0.594 compared with the first- and second-generation EGFR-TKIs. In the United States, the osimertinib ICERs were $226?527 vs erlotinib, $231?123 vs gefitinib, and $219?874 vs afatinib. In Brazil, the ICERs were $162?329, $180?804, and $175?432, respectively. The overall survival (95% CI) reported in the FLAURA trial (hazard ratio, 0.63; 95% CI, 0.45-0.88) had the strongest association with the ICER (ranging from $84?342 to $859?771). Osimertinib price adjustments to the FLAURA trial data improved cost-effectiveness. For example, a discount of 10% on osimertinib acquisition cost was associated with a 20% decreased ICER compared with the base case ICER, and a discount of 20% on osimertinib acquisition cost was associated with a 40% decreased ICER compared with the base case ICER. Conclusions and Relevance:At current costs, by World Health Organization cost-effectiveness threshold criteria, osimertinib is not cost-effective for first-line therapy of EGFR-mutated NSCLC in either the United States or Brazil.

Project description:BackgroundActivated epidermal growth factor receptor (EGFR) mutation is the main pathogenic cause of non-small cell lung cancer (NSCLC) in Asia. However, the impact of plasma EGFR mutation abundance, especially of the ultra-low abundance of EGFR mutation detected by highly sensitive techniques on clinical outcomes of first-line EGFR tyrosine kinase inhibitors (TKIs) for advanced NSCLC patients remains unclear.MethodsWe qualitatively detected baseline EGFR status of NSCLC tissues using amplification-refractory mutation system and quantified the plasma abundance of EGFR mutations through next-generation sequencing (NGS). Every 8-12 weeks, we performed dynamic detection of plasma mutation abundance and imaging evaluation. We analyzed the association between plasma abundance of EGFR sensitizing mutations, tumor size, tumor shrinkage percentage, concomitant TP53 mutations, and clinical response to TKIs.ResultsThis prospective study enrolled 135 patients with advanced NSCLC. The objective response rate (ORR) and disease control rate (DCR) for EGFR mutation-positive patients were 50.0% and 87.0%, respectively. When the cutoff value of plasma EGFR mutation abundance was 0.1%, the ORRs of TKI-treated patients were significantly different (60.0% for the >0.1% group vs. 21.4% for the ≤0.1% group, P=0.028). Median progression-free survival (PFS) was significantly longer for participants with a mutation abundance above 0.1% compared to those with a 0.01-0.1% abundance (log rank, P=0.0115). There was no significant association between plasma abundance of EGFR sensitizing mutations and tumor size, tumor shrinkage percentage, or concomitant TP53 mutations. Cox multivariate analysis demonstrated that plasma mutation abundance was an independent predictive factor for PFS [hazard ratio (HR) 2.41, 95% confidence interval (CI): 1.12-5.20; P=0.025]. We identified 11 participants with the acquired T790M resistance mutation according to serial dynamic plasma samples.ConclusionsLiquid biopsy screening based on highly sensitive NGS is reliable for detecting drug resistance and actionable somatic mutations. The plasma abundance of the EGFR driver mutation affected clinical response to EGFR-TKIs in advanced NSCLC patients; prolongation of PFS was also observed in patients with an ultra-low abundance of EGFR sensitizing mutations.

Project description:PurposeA meta-analysis of randomized controlled trials (RCTs) was conducted to compare the difference in efficacy and safety between epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) with antiangiogenic inhibitors (A + T) and EGFR-TKI monotherapy in patients with treatment-naïve advanced EGFR-mutant non-small-cell lung cancer (NSCLC).MethodsPubMed, Embase, Web of Science, and Cochrane electronic databases were searched for relevant RCTs. Meeting abstracts were also reviewed to identify appropriate studies. The endpoints included progression-free survival (PFS), overall survival (OS), 1- and 2-year OS rates, objective response rate (ORR), and grade ? 3 adverse events. All pooled outcomes were expressed using hazard ratios (HRs) or relative risk ratios (RRs).ResultsData were collected from six eligible RCTs, which included 1,244 participants (619 in the A + T group and 625 in the TKI alone group). PFS was significantly improved with A + T compared to TKI alone (HR = 0.60; P < 0.01) regardless of EGFR mutation types (exon 19 deletion or L858R) and brain metastasis status (with or without brain metastases). There was no significant difference in median OS between the A + T and TKI alone groups (HR = 0.933; P = 0.551) regardless of EGFR mutation type. The ORR for A + T combination therapy was significantly increased compared to TKI monotherapy in exon 19 deletion subgroups (RR = 0.774; P = 0.008). There was no difference in the positive rates of acquired T790M mutation between the two groups (RR = 0.967; P = 0.846). More patients in the TKI alone group received a variety of subsequent systemic treatments than those in the A + T group (RR = 0.881; P = 0.002).ConclusionAddition of antiangiogenic inhibitors to first-line EGFR-TKI therapy significantly reduced the risk of disease progression for patients with advanced EGFR-mutant NSCLC regardless of EGFR mutation type and brain metastasis status. The lack of OS benefit may be explained by differences in subsequent treatments rather than drug resistance mechanisms.

Project description:ObjectiveTo investigate the cost-effectiveness of ramucirumab plus erlotinib compared with placebo plus erlotinib in the first-line setting for patients with EGFR-mutated metastatic non-small cell lung cancer (mNSCLC) from the Chinese healthcare system perspective.DesignA Markov model consisting of three health states using clinical survival data from the RELAY phase III randomised clinical trial, a lifetime horizon for costs and quality-adjusted life-years (QALYs) was constructed to analyse the cost-effectiveness of ramucirumab plus erlotinib. One-way and probabilistic sensitivity analyses were performed to evaluate the robustness of the model. Additional price reduction scenario analyses were performed.SettingThe Chinese healthcare system perspective.ParticipantsA hypothetical Chinese cohort of patients with confirmed previously documented ex19del or Leu858Arg mutation stage IV NSCLC, and without known epidermal growth factor receptor (EGFR) Thr790Met mutation and central nervous system metastases.InterventionsRamucirumab plus erlotinib versus placebo plus erlotinib.Primary outcome measureCosts, QALYs, incremental cost-effectiveness ratio (ICER).ResultsIn base-case analysis, ramucirumab plus erlotinib yield an additional 4.21 QALYs at a cost of $540 590, resulting in an ICER of $128 302/QALY. In price reduction scenario analysis, the ICER ($65 227/QALY) was decreased significantly when the National Reimbursement Drug List (NRDL) negotiation was available for ramucirumab, and the ICER ($131 554/QALY) was increased slightly when the NRDL negotiation was unavailable for erlotinib. Sensitivity analyses demonstrated our results to be most sensitive to the unit cost of ramucirumab (10 mg/kg), and more than 52.1% reduction in the price of ramucirumab resulted in the ICER under the willingness-to-pay threshold set for affluent regions ($70 353/QALY).ConclusionsRamucirumab plus erlotinib is unlikely to be cost-effective for patients with untreated EGFR-mutated mNSCLC in China. Reducing the price of ramucirumab through the National Healthcare Security Administration negotiation was found to be the most realistic action to improve cost-effectiveness.

Project description:ObjectivesTo explore the rationale and value of consolidative cranial local therapy (CLT) in epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) patients with brain metastases (BMs).MethodsEGFR-mutant NSCLC patients with baseline BMs who received first-line EGFR-tyrosine kinase inhibitors (TKIs) at two academic centers from May 2015 to June 2020 were retrospectively enrolled. Patterns of tumor response and treatment failure were extensively analyzed in order to explore the rationale of CLT. Cranial lesions with number ⩽3 and largest tumor size ⩽3 cm at baseline and best response to EGFR-TKIs were defined as oligo-BMs and oligo-residual cranial disease (ORCD), respectively. To provide preliminary data supporting CLT, survival outcomes were compared in patients with ORCD, stratified by CLT status.ResultsOf the 216 patients enrolled, 57.1% had oligo-BMs and 24.5% received first-line osimertinib. At best response to the first-line EGFR-TKIs, intracranial complete response, partial response, and stable disease occurred in 18.5, 31.9, and 44.4% of the whole population, respectively. For patients without CLT (n = 193), ORCD was observed in 78.1% of the 105 patients with baseline oligo-BMs and 10.2% of the 88 patients with baseline multiple-BMs. With a median follow-up of 22.8 months, 107 patients had cranial first progressive disease (PD); more than 60% developed their first PD solely from the residual tumor sites at best response to EGFR-TKIs. Moreover, among patients with ORCD (n = 108), patients who received CLT (n = 17) achieved significantly longer progression-free survival (13.4 versus 8.5 months, p = 0.001) and overall survival (58.9 versus 28.8 months, p = 0.021) than those without CLT. Meanwhile, CLT remained as an independent prognostic factor associated with improved survival after Cox regression analyses.ConclusionsCranial progressive disease developed mostly at the residual cranial lesions in EGFR-mutant NSCLC patients with baseline BMs who received first-line EGFR-TKIs. Consolidative cranial local therapy targeting the oligo-residual cranial tumor lesions may provide survival benefit, which warrants future validation.

Dataset Information

Cost-effectiveness analysis of the first-line EGFR-TKIs in patients with non-small cell lung cancer harbouring EGFR mutations.

Objectives

Methods

Results

Conclusions

Publications

Cost-effectiveness analysis of the first-line EGFR-TKIs in patients with non-small cell lung cancer harbouring EGFR mutations.

Similar Datasets

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