The cost-effectiveness of dacomitinib in first-line treatment of advanced/metastatic epidermal growth factor receptor mutation-positive non-small-cell lung cancer (EGFRm NSCLC) in Sweden

Abstract

Aims: Although the benefit of first-line epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) over chemotherapy in EGFR mutation-positive (EGFRm) non-smallcell lung cancer (NSCLC) has been demonstrated in clinical trials, the optimal treatment sequence remains unclear. The objective of our study was to evaluate the cost-effectiveness of dacomitinib in Sweden versus afatinib and osimertinib in first-line treatment of EGFRm NSCLC. Materials and methods: A partitioned survival model was developed with three health states: progression-free, post-progression, and death. Progression-free and overall survival curves were used to inform movements between states. Clinical data were taken from randomized trials, compared via a network meta-analysis (NMA). Utility data were taken from published studies and costs from national Swedish sources. The model used a 15-year time horizon and a Swedish healthcare payer perspective. Sensitivity and scenario analyses were performed. Results: The base-case analysis showed that dacomitinib accrued a total of 2.10 qualityadjusted life years (QALYs) at a total cost of Swedish krona (SEK) 874,615. The incremental cost-effectiveness ratio (ICER) for dacomitinib versus afatinib was SEK 461,556 per QALY gained. The ICER of osimertinib versus dacomitinib, where the small QALY gains of the former came at a high additional cost, was SEK 11,444,709. Deterministic and probabilistic sensitivity analyses confirmed robustness of these results; changes to drug and medical resource use costs and overall survival had the greatest impact on ICER estimates. Limitations: This model is subject to uncertainty associated with extrapolating long-term A c c e p t e d M a n u s c r i p t treatment effects from shorter trial follow-up periods, although this would also be a limitation when using direct comparison or time-dependent hazard ratios. The NMA was limited by the use of indirect comparison although sensitivity analyses supported the robustness of our findings. Conclusions: Our model demonstrated dacomitinib is cost-effective for first-line EGFRm NSCLC treatment in Sweden versus afatinib and osimertinib.

Cost-Effectiveness Analysis of Five Systemic Treatments for Unresectable Hepatocellular Carcinoma in China: An Economic Evaluation Based on Network Meta-Analysis

“…With no direct randomized controlled trials between groups of drugs, indirect comparisons are necessary. Most previous studies (18,29,(32)(33)(34)(35)(36)(37)(38) have used a common control drug as a bridge and adopted the constant HR assumption. This method requires that the KM curves of the test group and control group obey the assumption of equal proportions.…”

“…In addition, we closely modeled the observed the Kaplan-Meier curves and constructed a network meta-analysis based on the FP model with which time-varying HRs were calculated. This analysis is necessary given that nonproportional hazards were detected in the chosen trials, which has not been addressed by previous reviews (35)(36)(37)(38).…”

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

“…All 59 studies included an EGFR TKI as an intervention; this was considered appropriate given the focus of the identified studies in patients harboring an EGFR mutation. The most frequently evaluated interventions were osimertinib ( n = 18) [ 30 , 32 , 34 , 35 , 38 , 40 , 44 , 47 , 50 , 51 , 55 , 62 , 68 , 71 , 73 , 78 , 83 , 88 ], dacomitinib ( n = 14) [ 31 , 32 , 40 , 42 , 43 , 47 , 52 , 53 , 63 , 67 , 72 , 74 , 82 , 87 ], afatinib ( n = 17) [ 32 , 33 , 36 , 39 , 40 , 45 , 46 , 56 , 57 , 59 , 65 , 66 , 69 , 70 , 77 , 80 , 86 ], gefitinib ( n = 12) [ 33 , 37 , 40 , 41 , 49 , 50 , 54 , 65 , 69 , 75 , 81 , 84 ], and erlotinib ( n = 12) [ 32 , 40 , 50 , ...…”

“…Twenty-eight studies did not state the rationale for the choice of comparator [ 30 , 33 , 35 , 36 , 38 , 39 , 41 – 43 , 45 , 46 , 48 , 52 , 54 , 56 – 63 , 65 – 68 , 72 , 76 ]. In the remaining 31 studies, comparators were selected to reflect standard of care, which was defined as commonly used regimens or licensed treatment [ 31 , 32 , 34 , 37 , 40 , 44 , 47 , 49 – 51 , 53 , 55 , 64 , 69 – 71 , 73 – 75 , 77 – 88 ]. Only one of these studies also included comparator regimens that were investigational in order to provide a comprehensive picture of possible treatment options [ 40 ].…”

“…Most were cost-utility analyses ( n = 52) [ 30 – 32 , 34 – 44 , 46 – 50 , 52 , 53 , 55 – 79 , 81 – 95 ], four were cost-effectiveness analyses [ 33 , 45 , 51 , 54 ], one was a cost-minimization analysis [ 80 ], and two (both of which were HTA submissions) presented both a cost-utility and cost-minimization analysis depending on the comparator [ 76 , 81 ]. The choice of model type was only reported in two studies that used a cost-minimization analysis, to justify that model type, given there were no statistically significant differences in efficacy and safety between treatment options [ 80 , 81 ].…”