Incremental cost-effectiveness analysis of tyrosine kinase inhibitors in advanced non-small cell lung cancer with mutations of the epidermal growth factor receptor in Colombia.

OBJECTIVE: To estimate the cost-effectiveness of sequences starting with tyrosine kinase inhibitors (TKI), afatinib and osimertinib, for the treatment of epidermal growth factor receptor (EGFR) mutation-positive (Exon 19 deletion or L858R) non-small cell lung cancer (NSCLC), stages IIIB - IV in Colombia. METHODS: A partitioned survival model was designed, using information from global and progression-free survival curves. For first and second-generation TKI, second line treatment was assumed according to the presence of T790M mutation to define the use of osimertinib or chemotherapy. The cost of the states without progression and post-progression was estimated using the base case approach, identified through consultation with clinical experts. RESULTS: The cost of treatment starting with afatinib in the first line was of 222,247 USD (1 USD = 3171.99 COP) and produced 1.36 QALYs. The strategy with afatinib was dominant with respect to that of first line TKI (227,289 USD and 1.34 QALY). The strategy with osimertinib resulted in more QALYs and higher costs, with ICERs of 35,062 USD, exceeding the current willingness to pay threshold for Colombia. CONCLUSIONS: Treatment starting with afatinib in the first line is dominant with respect to the strategy with first line TKI. The ICER of osimertinib sequence exceeds the threshold when compared with afatinib one.

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).

Budget impact of sequential treatment with first-line afatinib versus first-line osimertinib in non-small-cell lung cancer patients with common EGFR mutations.

BACKGROUND: The therapeutic landscape for non-small-cell lung cancer (NSCLC) patients that have common epidermal growth factor receptor (EGFR) mutations has changed radically in the last decade. The availability of these treatment options has an economic impact, therefore a budget impact analysis was performed. METHODS: A budget impact analysis was conducted from a Dutch healthcare perspective over a 5-year time horizon in EGFR-mutant NSCLC patients receiving first-line afatinib (Gilotrif®) versus first-line osimertinib (Tagrisso®), followed by subsequent treatments. A decision analysis model was constructed in Excel. Scenario analyses and one-way sensitivity analysis were used to test the models' robustness. RESULTS: Sequential treatment with afatinib versus first-line treatment with osimertinib showed mean total time on treatment (ToT) of 29.1 months versus 24.7 months, quality-adjusted life months (QALMs) of 20.2 versus 17.4 with mean cost of €108,166 per patient versus €143,251 per patient, respectively. The 5-year total budget impact was €110.4 million for the afatinib sequence versus €158.6 million for the osimertinib sequence, leading to total incremental cost savings of €48.15 million. CONCLUSIONS: First-line afatinib treatment in patients with EGFR-mutant NSCLC had a lower financial impact on the Dutch healthcare budget with a higher mean ToT and QALM compared to osimertinib sequential treatment.

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.

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.

Cost-utility of afatinib and gefitinib as first-line treatment for EGFR-mutated advanced non-small-cell lung cancer.

AIM: To evaluate the cost-utility of gefitinib and afatinib as first-line EGFR-mutated non-small-cell lung cancer treatments from the Chinese healthcare system perspective. MATERIALS & METHODS: A Markov model was established, state transition probabilities were extracted from the LUX-Lung7 trial and utility values were from previous studies. The cost was extracted from local charge or relevant literature. Incremental cost-effectiveness ratio was calculated for intention-to-treat, EGFR exon 19 deletion (del19) and exon Leu858Arg (21L858R, L858R) muation subgroups.  Results: For the entire population, the afatinib regimen afforded additional 0.29 quality-adjusted life years (QALYs). Incremental cost-effectiveness ratios were US$9820.41/QALY, US$18,529.65/QALY and US$1585.51/QALY for intention-to-treat, L858R and del19, respectively. CONCLUSION: First-line afatinib was more cost-effective than gefitinib for EFGR-mutated advanced non-small-cell lung cancer in China.

Economic analysis of osimertinib in previously untreated EGFR-mutant advanced non-small cell lung cancer in Canada.

INTRODUCTION: Osimertinib improves progression-free survival in previously untreated EGFR-positive advanced non-small cell lung cancer (NSCLC) patients, with marked intracranial response rates. However, its cost-effectiveness in a publically funded health care system has not been established. We assessed the cost-effectiveness of first-line osimertinib from the public payer perspective in the Canadian health care system. METHODS: A Markov model was developed to project the outcomes and direct medical costs of initial treatment with osimertinib or current standard-of-care (SoC) EGFR TKIs, gefinitib or afatinib, in patients with previously untreated EGFR-mutant advanced NSCLC. Clinical and cost input estimates were informed from the available literature. Model outcomes included costs (in 2018 Canadian dollars), life years (LYs), quality-adjusted life-years (QALYs), and the cost utility of osimertinib compared to SoC EGFR TKI, or incremental cost per QALY gained. RESULTS: Initial treatment with osimertinib was associated with a gain of 0.79 QALY [95% confidence interval (CI), 0.74 to 0.83] at an incremental cost of $176,394 CAD (95% CI, 176,383 to 176,405) vs. SoC EGFR TKI (incremental cost-effectiveness ratio [ICER]: $223,133/QALY gained; 95%CI, 198,144 to 252,805). Osimertinib had a 0% probability of being cost-effective at a willingness-to-pay threshold of $100,000 per QALY. Deterministic sensitivity analysis showed that the cost of osimertinib had the largest impact on ICER results. CONCLUSION: At the current marketed price, first-line osimertinib therapy in patients with advanced EGFR-mutant lung adenocarcinoma is not cost-effective in Canada. Reduction of osimertinib cost, for example by 25%, can significantly improve the cost-effectiveness profile.

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.