Economic analysis of osimertinib in previously untreated EGFR-mutant advanced non-small cell lung cancer in Canada
Introduction
Lung cancer is the most common cause of cancer-related mortality worldwide. Up to 85% of lung cancer cases are due to non-small cell lung cancer (NSCLC), which often presents with advanced disease [1,2]. In recent years, targeted therapy with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) has revolutionized the care of advanced NSCLC patients demonstrating survival and quality of life improvement, with less adverse events than the historical standard of cytotoxic chemotherapy [[3], [4], [5]]. First-line treatment of patients with advanced EGFR-mutant NSCLC with first- or second-generation EGFR TKI therapy, such as gefitinib or afatinib, is currently approved and funded in the Canadian public healthcare system.
Osimertinib, a third generation EGFR TKI, is an oral, irreversible EGFR TKI that is selective for EGFR sensitizing and T790M resistance mutations. Osimertinib has been widely approved for use in patients who have progressed on initial EGFR TKI, and harbor a T790M resistance mutation [6]. Currently, osimertinib is approved for use in Canada only in the second-line setting, in patients with EGFR T790M-mutant NSCLC.
The AZD9291 Versus Gefitinib or Erlotinib in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer (FLAURA) trial is a landmark, phase III, double-blind, randomized trial comparing osimertinib to standard-of-care (SoC) EGFR TKI (either gefitinib or erlotinib) in patients with previously untreated EGFR-mutant NSCLC [7]. In this trial, osimertinib significantly prolonged progression-free survival (PFS) compared with SoC as first-line therapy (18.9 months vs. 10.2 months; hazard ratio for disease progression or death, 0.46; 95% confidence interval [CI], 0.37 to 0.57; P < 0.001). High intracranial response rates were also seen with osimertinib therapy in patients with CNS metastases. At interim analysis, there was a numerical overall survival (OS) trend in favor of osimertinib (hazard ratio for death, 0.63; 95% CI, 0.45 to 0.88; P = 0.007 [not statistically significant in the interim analysis]). The toxicity profile was more favorable in the osimertinib arm compared to gefitinib/erlotinib (Grade ≥3 adverse events 34% vs. 45%, respectively). However, despite these benefits, the list price for osimertinib is nearly four times that of gefitinib or afatinib [8]. Publically funded healthcare systems rely on health technology assessments (HTAs) to help determine value for money and support funding decisions for novel therapies. In a single-payer healthcare system like Canada, the cost-effectiveness of first-line osimertinib treatment compared to currently funded therapies is unknown. The purpose of this study is to evaluate the cost-effectiveness analysis of osimertinib compared with SoC EGFR TKI in patients with previously untreated EGFR-mutant advanced NSCLC in the province of Ontario, Canada.
Section snippets
Model structure
A Markov model was constructed using TreeAge Pro 2017 (Williams-town, MA) to simulate outcomes beyond the FLAURA trial period, and to estimate the incremental cost-effectiveness ratio (ICER) between the two treatment strategies, first-line osimertinib (arm 1) or SoC gefitinib or afatinib (arm 2). The target population was treatment-naïve patients with advanced EGFR-mutant lung cancer in the province of Ontario. Analysis was performed from the government payer perspective of the Canadian
Base case analysis
Treatment with first-line osimertinib was associated with 0.79 quality-adjusted life years (QALYs) (95% CI, 0.74 to 0.83) gained at an incremental cost of $176,394 (95% CI, 176,383 to 176,405). The incremental cost per QALY for osimertinib vs. gefitinib/afatinib was $223,133 per QALY (95%CI, 198,144 to 252,805). The gain in unadjusted life years (LYs) was 1.04. At a discounting rate of 0%, the gain in unadjusted LYs and ICER were 1.12 and $162,139 per LY expressed as point estimates,
Discussion
The rapidly escalating cost of newer, more effective cancer drugs is a worldwide dilemma. Over the past decade, targeted therapy with TKIs has revolutionized the care of patients with advanced EGFR-mutant lung cancer, demonstrating better survival, quality of life improvement and less toxicity than the historic standard of cytotoxic chemotherapy. Due to the increasing costs of novel therapies in advanced cancer, economic analyses are instrumental in guiding public funding and drug access
Funding
None.
Author contributions
Conception and design: Doreen A. Ezeife, Veronica Kirk, Derek S. Chew, Kelvin KW Chan, Natasha B. Leighl
Collection and assembly of data: Doreen A. Ezeife, Kelvin KW Chan, Roy Lee, Lisa W. Le, Natasha B. Leighl
Data analysis and interpretation: All authors
Manuscript writing: All authors
Final approval of manuscript: All authors
Accountable for all aspects of the work: All authors
Conflict of interest
Dr. Leighl reports grants, personal fees and non-financial support from Astra Zeneca for independent continuing medical education lectures, unrelated to the submitted work. Dr. Nixon reports grants and other from Pfizer, Novartix, Boehringer Ingelheim, unrelated to the submitted work.
Acknowledgement
None.
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Pattern of Recurrence Analysis in Metastatic EGFR-Mutant NSCLC Treated with Osimertinib: Implications for Consolidative Stereotactic Body Radiation Therapy
2020, International Journal of Radiation Oncology Biology PhysicsCitation Excerpt :Recently, osimertinib has been approved as first-line therapy for metastatic EGFR-mutant NSCLC in a number of countries. However, several studies have indicated that osimertinib may not be a cost-effective treatment option in either the first- or second-line setting in the United States, Canada, Brazil, or China.29-31 Second, unknown synergistic risks of combined SBRT and osimertinib are of potential concern, considering both treatment modalities carry the risk of treatment-related toxicities.