Elsevier

Lung Cancer

Volume 125, November 2018, Pages 1-7
Lung Cancer

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

https://doi.org/10.1016/j.lungcan.2018.08.024Get rights and content

Highlights

  • Osimertinib is effective for treating lung cancer with an EGFR mutation.

  • The cost-effectiveness of osimertinib in a public payer system was assessed.

  • At the current marketed price, first-line osimertinib is not cost-effective.

  • Osimertinib price reduction by 25% can improve the cost-effectiveness profile.

Abstract

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.

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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