Objectives To compare the cost-effectiveness of first-line gefitinib, erlotinib, afatinib, and osimertinib in patients with nonsmall 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.Keywords Cost-effectiveness analysis · Non-small cell lung cancer · EGFR-TKI · Gefitinib · Erlotinib · Afatinib · Osimertinib JEL Classification I19 · C59 · C69
Background EGFR-tyrosine kinase inhibitors (EGFR-TKIs) including afatinib, dacomitinib, erlotinib, gefitinib, and osimertinib have proven efficacy in terms of progression-free survival (PFS) in patients with non-small-cell lung cancer (NSCLC) harboring EGFR mutations. However, an overall view for comparing efficacy and toxicity on a meta-level is lacking. This study compared efficacy and toxicity of first-line treatment with five different EGFR-TKIs by conducting a network meta-analysis (NMA). Methods A systematic review was performed, aiming to find eligible literature. Data of PFS, overall survival (OS), objective response rate (ORR), and adverse events were extracted. An NMA based on Bayesian statistics was established to synthesize the efficacy and toxicity of all treatments. Results Thirteen randomized controlled trials, including data from 3,539 patients with EGFR-mutated NSCLC, were analyzed. Rank probabilities showed that osimertinib had a potentially better efficacy in terms of PFS and OS compared to all other TKIs. For ORR, afatinib and osimertinib showed a trend of superiority compared to the other four TKIs. Furthermore, there was a high risk of diarrhea and rash for patients treated with afatinib or dacomitinib as well as a moderate risk for treatment with erlotinib, gefitinib, and osimertinib. Conclusion Our study showed a favorable efficacy of osimertinib in terms of PFS and OS compared to all other EGFR-TKIs in patients with NSCLC harboring activating EGFR mutations. Furthermore, gefitinib, erlotinib, and osimertinib were associated with fewer toxicities compared to the other TKIs. Therefore, osimertinib is indicated as a preferable first-line TKI in patients with activating EGFR-mutated NSCLC.
Background: Risk-sharing arrangements (RSAs) can be used to mitigate uncertainty about the value of a drug by sharing the financial risk between payer and pharmaceutical company. We evaluated the projected impact of alternative RSAs for nonesmall cell lung cancer (NSCLC) therapies based on real-world data. Methods: Data on treatment patterns of Dutch NSCLC patients from four different hospitals were used to perform "what-if" analyses, evaluating the costs and benefits likely associated with various RSAs. In the scenarios, drug costs or refunds were based on response evaluation criteria in solid tumors (RECIST) response, survival compared to the pivotal trial, treatment duration, or a fixed cost per patient. Analyses were done for erlotinib, gemcitabine/cisplatin, and pemetrexed/platinum for metastatic NSCLC, and gemcitabine/cisplatin, pemetrexed/cisplatin, and vinorelbine/cisplatin for nonmetastatic NSCLC. Results: Money-back guarantees led to moderate cost reductions to the payer. For conditional treatment continuation schemes, costs and outcomes associated with the different treatments were dispersed. When price was linked to the outcome, the payer's drug costs reduced by 2.5% to 26.7%. Discounted treatment initiation schemes yielded large cost reductions. Utilization caps mainly reduced the costs of erlotinib treatment (by 16%). Given a fixed cost per patient based on projected average use of the drug, risk sharing was unfavorable to the payer because of the lower than projected use. The impact of RSAs on a national scale was dispersed. Conclusions: For erlotinib and pemetrexed/platinum, large cost reductions were observed with risk sharing. RSAs can mitigate uncertainty around the incremental costeffectiveness or budget impact of drugs, but only when the type of arrangement matches the setting and type of uncertainty.
Background Tauroselcholic [75selenium] acid (SeHCAT™) (GE Healthcare, Chicago, IL, USA) is a radiopharmaceutical that may be useful in diagnosing bile acid diarrhoea. Objectives To assess the clinical effectiveness and cost-effectiveness of SeHCAT for the investigation of adults with chronic unexplained diarrhoea, diarrhoea-predominant irritable bowel syndrome or functional diarrhoea (suspected primary bile acid diarrhoea), and adults with chronic diarrhoea and Crohn’s disease who have not undergone ileal resection (suspected secondary bile acid diarrhoea). Methods Sixteen databases were searched to November 2020. The review process included measures to minimise error and bias. Results were summarised by primary or secondary bile acid diarrhoea and study quality was considered. The cost-effectiveness analysis combined a short-term (6-month) decision-analytic model (diagnosis and initial treatment response) and a lifetime Markov model comprising three health states (diarrhoea, no diarrhoea and death), with transitions determined by probabilities of response to treatment. Analyses were conducted from an NHS and Personal Social Services perspective. Results Twenty-four studies were included in this review. Of these, 21 were observational studies, reporting some outcome data for patients treated with bile acid sequestrants, and in which only patients with a positive SeHCAT test were offered bile acid sequestrants. The median rate of response to bile acid sequestrants, among patients with a 7-day SeHCAT retention value of ≤ 15%, was 68% (range 38–86%) (eight studies). The estimated sensitivity of SeHCAT (≤ 15% threshold) to predict positive response to colestyramine was 100% (95% confidence interval 54.1% to 100%) and the specificity estimate was 91.2% (95% confidence interval 76.3% to 98.1%) (one study). The median proportion of treated patients who were intolerant/discontinued bile acid sequestrants was 15% (range 4–27%) (eight studies). There was insufficient information to determine whether or not intolerance varied between colestyramine, colestipol and colesevelam. For both populations, the SeHCAT 15% (i.e. a SeHCAT retention value of ≤ 15%) strategy dominated other strategies or resulted in incremental cost-effectiveness ratios of < £20,000–30,000 per quality-adjusted life-year gained. For the suspected primary bile acid diarrhoea population, SeHCAT 15% was the strategy most likely to be cost-effective: 67% and 73% probability at threshold incremental cost-effectiveness ratios of £20,000 and £30,000 per quality-adjusted life-year gained, respectively. For the Crohn’s disease population, these probabilities were 89% and 92% at £20,000 and £30,000 per quality-adjusted life-year gained, respectively. Cost-effectiveness was mostly led by treatment response. SeHCAT 15% was the strategy with the highest response rate in the majority of scenarios explored. Limitations and conclusions There is a lack of evidence linking the use of SeHCAT testing to patient-relevant outcomes. The optimal SeHCAT threshold, to define bile acid diarrhoea and select patients for treatment with bile acid sequestrants, is uncertain. It is unclear whether or not patients with ‘borderline’ or ‘equivocal’ 7-day SeHCAT retention values (e.g. between 10% and 15%) and patients with values of > 15% could benefit from treatment with bile acid sequestrants. Although the results of the economic evaluation conducted for both populations indicated that the SeHCAT 15% strategy dominated the other two strategies or resulted in incremental cost-effectiveness ratios that were lower than the common thresholds of £20,000 or £30,000 per quality-adjusted life-year gained, the paucity and poor quality of evidence mean that uncertainty is high. Future work The optimum study design would be a multiarm randomised controlled trial, in which participants meeting the inclusion criteria are randomised to receive colestyramine, colestipol, colesevelam or placebo, and all participants receive SeHCAT testing. Study registration This study is registered as PROSPERO CRD42020223877. Funding This project was funded by the National Institute for Health and Care Research (IHR) Evidence Synthesis programme and will be published in full in Health Technology Assessment; Vol. 26, No. 45. See the NIHR Journals Library website for further project information.
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