Osimertinib in Patients With Treatment-Naive EGFR-Mutant Non-small Cell Lung Cancer: Overall Survival, Post-progression Management and Budget Impact Analysis in Real-World.

INTRODUCTION: The observational multicenter prospective FLOWER study (NCT04965701) confirmed effectiveness and safety of osimertinib in the real-world (RW) management of untreated EGFR-mutant advanced non-small cell lung cancer (aNSCLC) patients. METHODS: Herein, we report updated survival data, post-progression management, cost/effectiveness and budget impact (BI) of osimertinib compared with a RW population receiving gefitinib or erlotinib. RESULTS: Overall, 189 Caucasian patients receiving first-line osimertinib were included. After a follow-up of 20.7 months, 74(39.2%) patients discontinued osimertinib, median time-to-treatment discontinuation (mTTD) was 27.9 months, overall survival 36.8 months. At progression, tissue biopsy was performed in 29 (56.9%), liquid biopsy in 15 (29.4%) and both in 7 (13.7%) cases. The most frequent resistant mechanism was MET amplification (N = 14, 29.8%). At data cutoff, 13 (6.9%) patients were continuing osimertinib beyond progression; 52 (67.5%) received second-line treatment; no further treatments were administered in 25 (32.5%) cases. Thirty-three (63.4%) patients received chemotherapy, 12(23.1%) TKIs combination. Cost-effectiveness analysis showed a total cost per patient based on RW mTTD of 98,957.34€, 21,726.28€ and 19,637.83€ for osimertinib, erlotinib and gefitinib, respectively. The incremental cost-effectiveness ratio (ICER)/month for osimertinib was 359,806.0€/life-year-gained (LYG) and 197,789.77€/LYG compared to erlotinib and gefitinib. For osimertinib, the BI-gap between RW-TTD and theoretical-TTD was 16,501.0€ per patient. CONCLUSIONS: This updated analysis confirms the effectiveness of osimertinib in RW. Although the ICER of osimertinib seems not cost-effective, additional costs for the management of disease progression to old generation TKIs were not considered in this study. The BI-gap suggests RW mTTD as a more reliable measure for expense estimation.

Cost-effectiveness analysis of first-line treatments for advanced epidermal growth factor receptor-mutant non-small cell lung cancer patients.

OBJECTIVES: Recent studies showed prolonged survival for advanced epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) patients treated with both monotherapies and combined therapies. However, high costs limit clinical applications. Thus, we conducted this cost-effectiveness analysis to explore an optimal first-line treatment for advanced EGFR-mutant NSCLC patients. MATERIALS AND METHODS: Survival data were extracted from six clinical trials, including ARCHER1050 (dacomitinib vs. gefitinib); FLAURA (osimertinib vs. gefitinib/erlotinib); JO25567 and NEJ026 (bevacizumab +erlotinib vs. erlotinib); NEJ009 (gefitinib +chemotherapy vs. gefitinib); and NCT02148380 (gefitinib +chemotherapy vs. gefitinib vs. chemotherapy) trials. Cost-related data were obtained from hospitals and published literature. The effect parameter (quality-adjusted life year [QALY]) was the reflection of both survival and utility. Incremental cost-effectiveness ratio (ICER), average cost-effectiveness ratio (ACER), and net benefit were calculated, and the willingness-to-pay (WTP) threshold was set at $30828/QALY from the perspective of the Chinese healthcare system. Sensitivity analysis was performed to explore the stability of results. RESULTS: We compared treatment groups with control groups in each trial. ICERs were $1897750.74/QALY (ARCHER1050), $416560.02/QALY (FLAURA), -$477607.48/QALY (JO25567), -$464326.66/QALY (NEJ026), -$277121.22/QALY (NEJ009), -$399360.94/QALY (gefitinib as comparison, NCT02148380), and -$170733.05/QALY (chemotherapy as comparison, NCT02148380). Moreover, ACER and net benefit showed that the combination of EGFR-TKI with chemotherapy and osimertinib was of more economic benefit following first-generation EGFR-TKIs. Sensitivity analyses showed that the impact of utilities and monotherapy could be cost-effective with a 50% cost reduction. CONCLUSION: First-generation EGFR-TKI therapy remained the most cost-effective treatment option for advanced EGFR-mutant NSCLC patients. Our results could serve as both a reference for both clinical practice and the formulation of medical insurance reimbursement.

Cost-effectiveness of osimertinib versus standard EGFR-TKI as first-line treatment for locally advanced or metastatic EGFR mutation-positive non-small cell lung cancer in Australia.

Objectives: To assess the cost-effectiveness of osimertinib versus standard epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), gefitinib or erlotinib, as first-line treatment for patients with locally advanced or metastatic EGFR mutation-positive non-small cell lung cancer in Australia from a healthcare system perspective.Methods: A partitioned survival model comprising three mutually exclusive health states with a five-year time horizon was developed. Model inputs were sourced from the pivotal trial (FLAURA) and published literature. Incremental cost-effectiveness ratios (ICERs), in terms of cost per quality-adjusted life-year (QALY) gained and cost per life-year (LY) gained, were calculated. Uncertainty of the results was assessed using deterministic and probabilistic sensitivity analyses.Results: Compared with standard EGFR-TKIs, osimertinib was associated with a higher incremental cost of A$118,502, and an incremental benefit of 0.274 QALYs and 0.313 LYs. The ICER was estimated to be A$432,197/QALY gained and A$378,157/LY gained. The base-case ICER was most sensitive to changes in cost of first-line osimertinib, time horizon, and choice of overall survival data (interim versus final analysis).Conclusions: At a willingness-to-pay threshold of A$50,000/QALY, first-line osimertinib is not cost-effective compared with standard EGFR-TKIs in Australia based on the current published price. To achieve acceptable cost-effectiveness, the cost of first-line osimertinib needs to be reduced by at least 68.4%.

Cost-effectiveness analysis of first and second-generation EGFR tyrosine kinase inhibitors as first line of treatment for patients with NSCLC harboring EGFR mutations.

BACKGROUND: Tyrosine-kinase inhibitors (TKIs) have become the cornerstone treatment of patients with non-small cell lung cancer that harbor oncogenic EGFR mutations. The counterpart of these drugs is the financial burden that they impose, which often creates a barrier for accessing treatment in developing countries. The aim if the present study was to compare the cost-effectiveness of three different first and second generation TKIs. METHODS: We designed a retrospective cost-effectiveness analysis of three different TKIs (afatinib, erlotinib, and gefitinib) administered as first-line therapy for patients with NSCLC that harbor EGFR mutations. RESULTS: We included 99 patients with the following TKI treatment; 40 treated with afatinib, 33 with gefitinib, and 26 with erlotinib. Median PFS was not significantly different between treatment groups; 15.4 months (95% CI 9.3-19.5) for afatinib; 9.0 months (95% CI 6.3- NA) for erlotinib; and 10.0 months (95% CI 7.46-14.6) for gefitinib. Overall survival was also similar between groups: 29.1 months (95% CI 25.4-NA) for afatinib; 27.1 months (95% CI 17.1- NA) for erlotinib; and 23.7 months (95% CI 18.6-NA) for gefitinib. There was a statistically significant difference between the mean TKIs costs; being afatinib the most expensive treatment. This difference was observed in the daily cost of treatment (p < 0.01), as well as the total cost of treatment (p = 0.00095). Cost-effectiveness analysis determined that afatinib was a better cost-effective option when compared with first-generation TKIs (erlotinib and gefitinib). CONCLUSION: In our population, erlotinib, afatinib, and gefitinib were statistically equally effective in terms of OS and PFS for the treatment of patients with advanced EGFR-mutated NSCLC population. Owing to its marginally increased PFS and OS, the cost-effectiveness analysis determined that afatinib was a slightly better cost-effective option when compared with first-generation TKIs (erlotinib and gefitinib).

Healthcare resource utilization and costs associated with patients prescribed afatinib or erlotinib as first-line therapy for EGFR mutation-positive NSCLC in the United States.

Aims: To assess healthcare resource utilization (HCRU) and costs in patients with non-small cell lung cancer treated with the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors afatinib or erlotinib as first-line treatment.Materials and methods: This retrospective analysis used data from three large administrative claims databases in the US: Truven MarketScan, IMS PharMetrics Plus, and Optum Clinformatics Data Mart. Patients with diagnosis codes of lung cancer treated with afatinib or erlotinib were included in the sample. Treatment cohorts were matched on baseline characteristics using propensity scores to account for potential selection bias. HCRU and healthcare costs were compared between the matched afatinib and erlotinib cohorts.Results: In total, 3,152 patients met the study inclusion criteria; propensity score matching of the afatinib and erlotinib patients yielded 525 matched pairs with well-balanced baseline characteristics. The afatinib cohort had significantly fewer patients with ≥1 inpatient visits (40.4% vs 52.2%, p = 0.0001) and outpatient emergency room (ER) visits (45.7% vs 54.1%, p = 0.0066). Per patient per month (PPPM) visits were significantly different between afatinib compared to erlotinib for inpatient visits (0.1 vs 0.2, p = 0.0152), other outpatient visits PPPM (2.6 vs 3.0, p = 0.022) and outpatient office visits (2.0 vs 1.7, p = 0.0059). Although costs of outpatient office ($1,624 vs $1,070; p = 0.0086) and pharmacy ($6,709 vs $5,932; p < 0.0001) visits were higher for afatinib vs erlotinib, total costs did not differ significantly between cohorts ($14,972 vs $14,412; p = 0.4415).Limitations: Retrospective claims data can be subject to coding errors or data omissions; patients were required to have continuous health plan enrolment; EGFR mutation status was not confirmed.Conclusions: Patients treated with afatinib as first-line monotherapy experienced fewer inpatient stays and ER visits compared with erlotinib. Total costs were not significantly different between the two treatment cohorts.

A comparative study on erlotinib & gefitinib therapy in non-small cell lung carcinoma patients.

Background & objectives: Tyrosine kinase inhibitors (TKIs) targeting the epidermal growth factor receptor (EGFR) have been evaluated in patients with advanced non-small cell lung cancer (NSCLC). Erlotinib and gefitinib are the first-generation EGFR-TKIs for patients with NSCLC. However, there is a paucity of studies comparing the effectiveness of these two drugs. Hence, this study was aimed to compare the effectiveness and safety of erlotinib and gefitinib in NSCLC patients. Methods: This study included 71 NSCLC patients who received EGFR-TKIs between 2013 and 2016. Adverse drug reaction of both erlotinib (n=37) and gefitinib (n=34) was determined and graded according to Common Terminology Criteria for Adverse Events grading system. Effectiveness was measured using response evaluation criteria in solid tumours and progression-free survival (PFS). Pharmacoeconomic analysis was performed by cost-effective analysis. Results: When comparing safety profile, both the drugs had similar adverse events except for dermal side effects such as acneiform eruption (51.4%), rash (54.05%) and mucositis (59.5%) for erlotinib and 20.6, 26.5 and 29.4 per cent for gefitinib, respectively. The PFS of the two drugs was compared to differentiate the effectiveness of erlotinib and gefitinib. There was no significant difference between the effectiveness of the two drugs. The pharmacoeconomic analysis showed that gefitinib was more cost-effective than erlotinib. Interpretation & conclusions: This study showed that erlotinib and gefitinib had similar effectiveness but gefitinib had a better safety profile compared to erlotinib. Therefore, gefitinib could be considered a better option for NSCLC patients compared to erlotinib. However, further studies need to be done with a large sample to confirm these findings.

How patent law reform can improve affordability and accessibility of medicines in South Africa: Four medicine case studies.

South Africa (SA) is in the process of amending its patent laws. Since its 2011 inception, Fix the Patent Laws, a coalition of 40 patient groups, has advocated for reform of SA's patent laws to improve affordability of medicines in the country. Building on two draft policies (2013, 2017) and a consultative framework (2016) for reform of SA's patent laws, Cabinet approved phase 1 of the Intellectual Property Policy of the Republic of South Africa on 23 May 2018. Fix the Patent Laws welcomed the policy, but highlighted concerns regarding the absence of important technical details, as well as the urgent need for government to develop bills, regulations and guidelines to provide technical detail and to codify and implement patent law reform in the country. In this article, we explore how reforms proposed in SA's new intellectual property policy could improve access to medicine through four medicine case studies.

The economic impact of the transition from branded to generic oncology drugs.

Background: Economic evaluations are an integral component of many clinical trials. Costs used in those analyses are based on the prices of branded drugs when they first enter the market. The effect of genericization on the cost-effectiveness (ce) or cost-utility (cu) of an intervention is unknown because economic analyses are rarely updated using the costs of generic drugs. Methods: We re-examined the ce or cu of regimens previously evaluated in Canadian Cancer Trials Group (cctg) studies that included prospective economic evaluations and where genericization has occurred or is anticipated in Canada. We incorporated the new costs of generic drugs to characterize changes in ce or cu. We also determined acceptable cost levels of generic drugs that would make regimens reimbursable in a publicly funded health care system. Results: The four randomized controlled trials included (representing 1979 patients) were cctg br.10 (early lung cancer, adjuvant vinorelbine-cisplatin vs. observation, n = 172), cctg br.21 (metastatic lung cancer, erlotinib vs. placebo, n = 731), cctg co.17 (metastatic colon cancer, cetuximab vs. best supportive care, n = 557), and cctg ly.12 (relapsed or refractory lymphoma, gemcitabine-dexamethasone-cisplatin vs. cytarabine-dexamethasone-cisplatin, n = 619). Since the initial publication of those trials, the genericization of vinorelbine, erlotinib, cetuximab, and cisplatin has taken place or is expected in Canada. Costs of generics improved the ces and cus of treatment significantly. For example, genericization of erlotinib ($1460.25 per 30 days) resulted in an incremental cost-effectiveness ratio (icer) of $45,746 per life-year gained compared with $94,638 for branded erlotinib. Likewise, genericization of cetuximab ($275.80 per 100 mg) produced an icer of $261,126 per quality-adjusted life-year (qaly) gained compared with $299,613 for branded cetuximab. Decreases in the cost of generic cetuximab to $129.39 and $63.51 would further improve the icer to $150,000 and $100,000 per QALY respectively. Conclusions: Genericization of a costly oncology drug can modify the ce and cu of a regimen significantly. Failure to revisit economic analyses with the costs of generics could be a missed opportunity for funding bodies to optimize value-based allocation of health care resources. At current levels, the costs of generics might not be sufficiently low to sustain publicly funded health care systems.

From Diagnostic-Therapeutic Pathways to Real-World Data: A Multicenter Prospective Study on Upfront Treatment for EGFR-Positive Non-Small Cell Lung Cancer (MOST Study).

INTRODUCTION: Gefitinib, erlotinib, and afatinib represent the approved first-line options for epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC). Because pivotal trials frequently lack external validity, real-world data may help to depict the diagnostic-therapeutic pathway and treatment outcome in clinical practice. METHODS: MOST is a multicenter observational study promoted by the Veneto Oncology Network, aiming at monitoring the diagnostic-therapeutic pathway of patients with nonsquamous EGFR-mutant NSCLC. We reported treatment outcome in terms of median time to treatment failure (mTTF) and assessed the impact of each agent on the expense of the regional health system, comparing it with a prediction based on the pivotal trials. RESULTS: An EGFR mutation test was performed in 447 enrolled patients, of whom 124 had EGFR mutation and who received gefitinib (n = 69, 55%), erlotinib (n = 33, 27%), or afatinib (n = 22, 18%) as first-line treatment. Because erlotinib was administered within a clinical trial to 15 patients, final analysis was limited to 109 patients. mTTF was 15.3 months, regardless of the type of tyrosine kinase inhibitor (TKI) used. In the MOST study, the budget impact analysis showed a total expense of €3,238,602.17, whereas the cost estimation according to median progression-free survival from pivotal phase III trials was €1,813,557.88. CONCLUSION: Good regional adherence and compliance to the diagnostic-therapeutic pathway defined for patients with nonsquamous NSCLC was shown. mTTF did not significantly differ among the three targeted TKIs. Our budget impact analysis suggests the potential application of real-world data in the process of drug price negotiation. IMPLICATIONS FOR PRACTICE: The MOST study is a real-world data collection reporting a multicenter adherence and compliance to diagnostic-therapeutic pathways defined for patients with epidermal growth factor receptor-mutant non-small cell lung cancer. This represents an essential element of evidence-based medicine, providing information on patients and situations that may be challenging to assess using only data from randomized controlled trials, e.g., turn-around time of diagnostic tests, treatment compliance and persistence, guideline adherence, challenging-to-treat populations, drug safety, comparative effectiveness, and cost effectiveness. This study may be of interest to various stakeholders (patients, clinicians, and payers), providing a meaningful picture of the value of a given therapy in routine clinical practice.

Determining the Comparative Value of Pharmaceutical Risk-Sharing Policies in Non-Small Cell Lung Cancer Using Real-World Data.

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 non-small 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 cost-effectiveness or budget impact of drugs, but only when the type of arrangement matches the setting and type of uncertainty.

A systematic review of pharmacoeconomic evaluations of erlotinib in the first-line treatment of advanced non-small cell lung cancer.

OBJECTIVE: To review and assess the quality of the available evidence on the cost-effectiveness of erlotinib in the first-line treatment of advanced non-small cell lung cancer (NSCLC). METHODS: A systematic review was conducted to identify full-text original economic evaluations of erlotinib in the first-line treatment of advanced NSCLC written in English and published from the year 2000 onwards. Study characteristics and results were recorded and compared. The quality of the studies was assessed by the Quality of Health Economic Studies (QHES) questionnaire. RESULTS: Eleven out of 130 papers were chosen for this review. Comparative regimens consisted of a best supportive care, reverse strategy, bevacizumab, cisplatin plus pemetrexed, carboplatin plus gemcitabine or gefitinib. The methods most used in these studies were modeling and sensitivity analysis and cost-effectiveness analysis. All of the studies evaluated direct costs and used quality-adjusted life-year (QALY) and life-years gained (LYG) as outcome, with 3% and 3.5% discount rate. The studies assigned ICER that ranged from dominant to I$305,510.31/QALY and from I$31,209.55/LYG to I$66,540.20/LYG. Based on the willingness to pay threshold, seven studies concluded that erlotinib was cost-effective, two studies showed that erlotinib was cost-effective on specific patients with certain conditions, and two studies comparing erlotinib with reverse strategy did not find a difference in cost-effectiveness. The high quality of these studies was confirmed using the QHES tool: the mean score was 75.77 out of 100 (SD 9.38). CONCLUSION: Most of these high-quality studies suggested that erlotinib was cost-effective in the first-line treatment of advanced NSCLC.

Effects of removing reimbursement restrictions on targeted therapy accessibility for non-small cell lung cancer treatment in Taiwan: an interrupted time series study.

INTERVENTIONS: Targeted therapies have been proven to provide clinical benefits to patients with metastatic non-small cell lung cancer (NSCLC). Gefitinib was initially approved and reimbursed as a third-line therapy for patients with advanced NSCLC by the Taiwan National Health Insurance (NHI) in 2004; subsequently it became a second-line therapy (in 2007) and further a first-line therapy (in 2011) for patients with epidermal growth factor receptor mutation-positive advanced NSCLC. Another targeted therapy, erlotinib, was initially approved as a third-line therapy in 2007, and it became a second-line therapy in 2008. OBJECTIVES: This study is aimed towards an exploration of the impacts of the Taiwan NHI reimbursement policies (removing reimbursement restrictions) related to accessibility of targeted therapies. SETTING: We retrieved 2004-2013 claims data for all patients with lung cancer diagnoses from the NHI Research Database. DESIGN AND OUTCOME MEASURES: Using an interrupted time series design and segmented regression, we estimated changes in the monthly prescribing rate by patient number and market shares by cost following each modification of the reimbursement policy for gefitinib and erlotinib for NSCLC treatment. RESULTS: Totally 92 220 patients with NSCLC were identified. The prescribing rate of the targeted therapies increased by 15.58%, decreased by 10.98% and increased by 6.31% following the introduction of gefitinib as a second-line treatment in 2007, erlotinib as a second-line treatment in 2008 and gefitinib as as first line treatment in 2011, respectively. The average time to prescription reduced by 65.84% and 41.59% following coverage of erlotinib by insurance and gefitinib/erlotinib as second-line treatments in 2007-2008 and following gefitinib as the first-line treatment in 2011. CONCLUSIONS: The changes in reimbursement policies had a significant impact on the accessibility of targeted therapies for NSCLC treatment. Removing reimbursement restrictions can significantly increase the level and the speed of drug accessibility.

Cost-effectiveness of Osimertinib as First-line Treatment and Sequential Therapy for EGFR Mutation-positive Non-small Cell Lung Cancer in China.

PURPOSE: This study aimed to evaluate the cost-effectiveness of osimertinib with gefitinib or erlotinib as first-line and sequential therapy for epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) in China. METHODS: The Markov model was used, and the study included 3 health states over a 10-year period. Transition probabilities and safety data were collected from the FLAURA (AZD9291 versus gefitinib or erlotinib in patients with locally advanced or metastatic Non-small Cell Lung Cancer) trial. Cost and utility values were derived from local charges and literature. Sensitivity analyses were performed to observe model stability. FINDINGS: The strategy with gefitinib or erlotinib first-line therapy and second-line gene-guided osimertinib therapy (GE-T790M) resulted in a gain of 0.31 quality-adjusted life year (QALY) at a cost of $15,200.95 per patient compared with the gefitinib or erlotinib first-line therapy and second-line chemotherapy (GE-chemotherapy). The incremental QALY and incremental cost values for first-line osimertinib therapy compared with GE-chemotherapy was 0.96 and $69,420.76, respectively. Compared with the GE-T790M strategy (0.96 QALY and $29,223.33), first-line osimertinib was estimated to be more effective (1.61 QALYs) and more costly ($83,443.14). Relative to the GE-chemotherapy strategy, the incremental cost-effectiveness ratios were $47,873.96 and $71,954.08 per QALY gained with GE-T790M and the osimertinib first-line strategy. The incremental cost-effectiveness ratio for first-line osimertinib versus GE-T790M was estimated to be $83,766.61. The results were found to be robust for univariate and multivariable sensitivity analyses. IMPLICATIONS: Gefitinib or erlotinib first-line and chemotherapy second-line strategies were the most cost-effective first-line treatments for EGFR mutations in patients with NSCLC. Gefitinib or erlotinib first-line and gene-guided osimertinib second-line strategies were more cost-effective than osimertinib first-line treatment for patients who preferred osimertinib administration in China.

Cost-effectiveness of afatinib and erlotinib as second-line treatments for advanced squamous cell carcinoma of the lung.

AIM: To investigate the cost-effectiveness of afatinib and erlotinib as second-line therapy for advanced squamous cell carcinoma of the lung. MATERIALS & METHODS: A decision-analytic model was developed for projecting the economic outcomes. Clinical parameters and utilities were from the LUX-Lung 8 trial. Costs were mainly estimated from the Chinese health system. The outcome was the incremental cost-effectiveness ratio. RESULTS: The afatinib strategy generated additional 0.154 quality-adjusted life-years compared with erlotinib, with incremental costs of ¥16,852. Relative to erlotinib, afatinib resulted in an incremental cost-effectiveness ratio of ¥109,429 per quality-adjusted life-year gained. The overall survival time of afatinib had a considerable impact on the model outcomes. CONCLUSION: Afatinib is a cost-effective treatment option compared with erlotinib in patients with squamous cell carcinoma.

OPTIMAL and ENSURE trials-based combined cost-effectiveness analysis of erlotinib versus chemotherapy for the first-line treatment of Asian patients with non-squamous non-small-cell lung cancer.

OBJECTIVES: Erlotinib, the first generation of epidermoid growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), has been recommended as an essential treatment in patients with non-small-cell lung cancer (NSCLC) with EGFR mutation. Although it has improved progression-free survival (PFS), overall survival (OS) was limited and erlotinib can be expensive. This cost-effectiveness analysis compares erlotinib monotherapy with gemcitabine-included doublet chemotherapy. SETTING: First-line treatment of Asian patients with NSCLC with EGFR mutation. METHODS: A Markov model was created based on the results of the ENSURE (NCT01342965) and OPTIMAL (CTONG-0802) trials which evaluated erlotinib and chemotherapy. The model simulates cancer progression and all causes of death. All medical costs were calculated from the perspective of the Chinese healthcare system. MAIN OUTCOME MEASURES: The primary outcomes are costs, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs). RESULTS: The combined PFS was 11.81 months and 5.1 months for erlotinib and chemotherapy, respectively, while the OS was reversed at 24.68 months for erlotinib and 26.16 months for chemotherapy. The chemotherapy arm gained 0.13 QALYs compared with erlotinib monotherapy (1.17 QALYs vs 1.04 QALYs), while erlotinib had lower costs ($55 230 vs $77 669), resulting in an ICER of $174 808 per QALY for the chemotherapy arm, which exceeds three times the Chinese GDP per capita. The most influential factors were the health utility of PFS, the cost of erlotinib and the health utility of progressed disease. CONCLUSION: Erlotinib monotherapy may be acceptable as a cost-effective first-line treatment for NSCLC compared with gemcitabine-based chemotherapy. The results were robust to changes in assumptions. TRIAL REGISTRATION NUMBER: NCT01342965 and CTONG-0802.

Factors Associated with Adherence to and Treatment Duration of Erlotinib Among Patients with Non-Small Cell Lung Cancer.

BACKGROUND: In lung cancer, there is an increasing number of oral agents available for patients; however, little is known about the factors associated with adherence to and treatment duration on oral medications in non-small cell lung cancer (NSCLC). OBJECTIVE: To evaluate the clinical and demographic factors associated with adherence and treatment discontinuation, respectively, to oral oncolytics among patients with NSCLC. METHODS: A retrospective, claims-based analysis of the Humana Research Database supplemented with medical chart review was conducted among patients with NSCLC who started an oral oncolytic between January 1, 2008, and June 30, 2013. Patients were required to be enrolled at least 1 year before the start of oral oncolytics and have no evidence of any oral oncolytic use during this period. Logistic regression models and Cox proportional hazard models were used to identify predictors associated with medication adherence and treatment duration, respectively. RESULTS: Among all oral oncolytics, only the cohort starting on erlotinib had sufficient sample size (n = 1,452). A wide variety of factors were found to be associated with adherence. Low-income subsidy status, previous use of intravenous chemotherapy, and lower total baseline health care costs were significantly related to decreasing adherence (each P < 0.05). Additionally, increasing patient out-of-pocket cost was associated with decreasing adherence to erlotinib (P < 0.0001). Factors significantly related to longer treatment duration included low-income subsidy status (P < 0.001) and having Medicare insurance, (P = 0.0004), dual eligibility (Medicare and Medicaid, P = 0.007), and higher erlotinib out-of-pocket costs (P < 0.0001). CONCLUSIONS: There is a need for mechanisms to be in place to identify and address barriers to care. Future research should focus on evaluating and reducing any potential risk to patient outcomes that may be associated with low adherence to or shorter treatment duration on oral chemotherapy. DISCLOSURES: This study was supported by funding from Eli Lilly and Company to Comprehensive Health Insights, a Humana company, as a collaborative research project involving employees of both companies. Hess, Winfree, Zhu, and Oton are employees of Eli Lilly and Company. Louder and Nair are employees of Comprehensive Health Insights, which received funding to complete this research. Study concept and design were contributed by Hess, Zhu, Winfree, and Oton. Nair and Louder collected the data, and data interpretation was performed by all the authors. The manuscript was written primarily by Hess, along with Nair, and revised by Hess, Nair, Louder, and Winfree, with assistance from Zhu and Louder.

Patient response to use of tyrosine kinase inhibitors in lung cancer: a retrospective audit during funding changes.

BACKGROUND: The New Zealand Pharmaceutical Management Agency (PHARMAC) approved funding of erlotinib in October 2010 as second line therapy in all non-squamous non-small cell lung cancer after platinum-based chemotherapy with no requirement for epidermal growth factor (EGFR) mutation testing. Funding widened in August 2012 to include gefitinib as first line treatment for patients with a proven EGFR mutation. Then in January 2014, both tyrosine kinase inhibitors (TKIs) were approved for first line treatment, but only for disease with EGFR mutation. AIM: To report the clinical experience with TKIs in a New Zealand tertiary referral centre over a period of funding change. METHOD: Retrospective audit of all patients commenced on erlotinib from 1st October 2010 until 1st November 2011, and gefitinib from 1st August 2012 until 31st August 2013. Follow-up was two years for both groups. RESULTS: Each group had 42 patients. Median Progression Free Survival was 76 days in the erlotinib group and 255 days in the gefitinib group. Twenty-eight percent of erlotinib patients had grade 3 adverse events with one treatment related death; fourteen percent of gefitinib patients had grade 3 adverse events. Dose reduction or treatment breaks were required in 12% in each group. CONCLUSION: Response rate in these audits appear to reflect the change in funding criteria, with improved response rates likely to be associated with more targeted treatment.

Economic Evaluation of Companion Diagnostic Testing for EGFR Mutations and First-Line Targeted Therapy in Advanced Non-Small Cell Lung Cancer Patients in South Korea.

BACKGROUND: As targeted therapy becomes increasingly important, diagnostic techniques for identifying targeted biomarkers have also become an emerging issue. The study aims to evaluate the cost-effectiveness of treating patients as guided by epidermal growth factor receptor (EGFR) mutation status compared with a no-testing strategy that is the current clinical practice in South Korea. METHODS: A cost-utility analysis was conducted to compare an EGFR mutation testing strategy with a no-testing strategy from the Korean healthcare payer's perspective. The study population consisted of patients with stage 3b and 4 lung adenocarcinoma. A decision tree model was employed to select the appropriate treatment regimen according to the results of EGFR mutation testing and a Markov model was constructed to simulate disease progression of advanced non-small cell lung cancer. The length of a Markov cycle was one month, and the time horizon was five years (60 cycles). RESULTS: In the base case analysis, the testing strategy was a dominant option. Quality-adjusted life-years gained (QALYs) were 0.556 and 0.635, and total costs were $23,952 USD and $23,334 USD in the no-testing and testing strategy respectively. The sensitivity analyses showed overall robust results. The incremental cost-effectiveness ratios (ICERs) increased when the number of patients to be treated with erlotinib increased, due to the high cost of erlotinib. CONCLUSION: Treating advanced adenocarcinoma based on EGFR mutation status has beneficial effects and saves the cost compared to no testing strategy in South Korea. However, the cost-effectiveness of EGFR mutation testing was heavily affected by the cost-effectiveness of the targeted therapy.

Inequalities in lung cancer: a world of EGFR.

Epidermal growth factor receptor gene (EGFR) mutation status has emerged as a crucial issue in lung cancer management. Availability and cost of tests and tyrosine kinase inhibitors (TKIs) may vary as a function of country development.We conducted a prospective specialist opinion survey to map EGFR test and EGFR-TKI availability and detect associations with the Human Development Index (HDI). A questionnaire was sent to specialists in thoracic oncology in all United Nations Member States.We obtained responses from 74 countries, comprising 78% of the worldwide population. Nonresponding countries had significantly lower HDI rank than responding countries. EGFR mutation analysis was routinely available in 57 countries (70% of the worldwide population). The cost of the test was