Critical Examination of Modeling Approaches Used in Economic Evaluations of First-Line Treatments for Locally Advanced or Metastatic Non-Small Cell Lung Cancer Harboring Epidermal Growth Factor Receptor Mutations: A Systematic Literature Review.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, with up to 32% of patients with NSCLC harboring an epidermal growth factor receptor (EGFR) mutation. NSCLC harboring an EGFR mutation has a dedicated treatment pathway, with EGFR tyrosine kinase inhibitors and platinum-based chemotherapy often being the therapy of choice. OBJECTIVE: The aim of this study was to systemically review and summarize economic models of first-line treatments used for locally advanced or metastatic NSCLC harboring EGFR mutations, as well as to identify areas for improvement for future models. METHODS: Literature searches were conducted via Ovid in PubMed, MEDLINE, MEDLINE In-Process, Embase, Evidence-Based Medicine Reviews: Health Technology Assessment, Evidence-Based Medicine Reviews: National Health Service Economic Evaluation Database, and EconLit. An initial search was conducted on 19 December 2022 and updated on 11 April 2023. Studies were selected according to predefined criteria using the Population, Intervention, Comparator, Outcome and Study design (PICOS) framework. RESULTS: Sixty-seven articles were included in the review, representing 59 unique studies. The majority of included models were cost-utility analyses (n = 52), with the remaining studies being cost-effectiveness analyses (n = 4) and a cost-minimization analysis (n = 1). Two studies incorporated both a cost-utility and cost-minimization analysis. Although the model structure across studies was consistently reported, justification for this choice was often lacking. CONCLUSIONS: Although the reporting of economic models in NSCLC harboring EGFR mutations is generally good, many of these studies lacked sufficient reporting of justification for structural choices, performing extensive sensitivity analyses and validation in economic evaluations. In resolving such gaps, the validity of future models can be increased to guide healthcare decision making in rare indications.

The cost-effectiveness of brigatinib in adult patients with ALK inhibitor-naive ALK-positive non-small cell lung cancer from a US perspective.

BACKGROUND: The discovery of specific oncogenic drivers in non-small cell lung cancer (NSCLC) has led to the development of highly targeted anaplastic lymphoma kinase tyrosine kinase inhibitors (ALKis). Brigatinib is a next-generation ALKi associated with prolonged progression-free survival in patients with ALKi-naive ALK+ NSCLC. OBJECTIVE: To estimate the cost-effectiveness of brigatinib compared with crizotinib and alectinib in patients with ALKi-naive ALK+ NSCLC, from a US payer perspective. METHODS: A lifetime area under the curve-partitioned survival model with 4 health states was used to evaluate the relative cost-effectiveness of brigatinib in the ALKi-naive ALK+ NSCLC setting. Brigatinib was compared with crizotinib within a cost-effectiveness framework and compared with alectinib in a cost-comparison framework, where all efficacy outcomes were assumed equal. The efficacy of brigatinib and crizotinib was informed by the ALTA-1L trial, and an indirect treatment comparison was performed to inform the efficacy of brigatinib vs alectinib owing to a lack of head-to-head data. Costs were derived from public sources. The main outcomes of the model were total costs, quality-adjusted life-years (QALYs), life-years, and incremental cost-effectiveness ratios. Univariate and probabilistic sensitivity analyses, in addition to multiple scenario analyses, were conducted to assess the robustness of the model outcomes. RESULTS: The improved outcomes observed in ALTA-1L translated into QALY gains (+0.97) in the comparison of brigatinib vs crizotinib. The superior efficacy profile was associated with increased time on treatment with brigatinib, which drove the increase in costs vs crizotinib (+$210,519). The resulting base-case incremental cost-effectiveness ratio was $217,607/QALY gained. Compared with alectinib, brigatinib was associated with a cost difference of -$8,546. Sensitivity analysis suggested that extrapolation of overall survival, the assumptions relating to time on treatment, and subsequent therapy costs were the most influential determinants of results. Probabilistic sensitivity analysis suggested brigatinib had the highest probability of being cost-effective beyond willingness-to-pay thresholds of $236,000 per QALY vs crizotinib and alectinib. CONCLUSIONS: At list prices and under base-case assumptions in the current analysis, brigatinib was associated with cost-savings vs alectinib, and QALY gains but at higher costs vs crizotinib. Additional research into the real-world efficacy of ALKis is warranted to further understand the comparative cost-effectiveness of these therapies. DISCLOSURES: Ms Cranmer and Ms Kearns are employees of Takeda UK Ltd. Dr Young is a former employee of Takeda Pharmaceuticals America, Inc. Dr Humphries is an employee of Takeda Pharmaceuticals U.S.A., Inc. Mr Trueman is an employee of Source Health Economics, the consultancy company that provided health economic and writing services. This work was funded by ARIAD Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. Work by Source Health Economics was funded by ARIAD Pharmaceuticals, Inc. Professional medical writing assistance was provided by Phillipa White, of Source Health Economics, and funded by ARIAD Pharmaceuticals, Inc.