Cost-effectiveness analysis of osimertinib for first-line treatment of locally advanced or metastatic EGFR mutation positive non-small cell lung cancer in Singapore

Abstract

Objective: Non-small cell lung cancer (NSCLC) accounts for 80-90% of all lung cancer cases and is usually associated with a poor prognosis. However, targeted therapy with first and second generation tyrosine kinase inhibitors (TKIs) has so far improved progression-free survival of epidermal growth factor receptor (EGFR) mutant NSCLC patients. Osimertinib, a third generation EGFR TKI has recently shown improved overall survival of 6.8 months in previously untreated EGFR mutant NSCLC patients. We assessed the cost-effectiveness of osimertinib versus standard EGFR TKIs (gefitinib or erlotinib) as first-line treatment for advanced or metastatic EGFR mutant NSCLC patients in Singapore. Methods: A partitioned survival model with three health states (progression-free, progressive disease, and death) was developed from the Singapore healthcare payer perspective. Survival curves based on the overall trial population from the FLAURA trial were extrapolated beyond trial period over a 10-year time horizon to estimate the underlying progression-free survival and overall survival parametric distributions. Health state utilities were derived from the literature and direct costs were sourced from public healthcare institutions in Singapore. Deterministic and probabilistic sensitivity analyses were conducted to explore the impact of uncertainties and assumptions on cost-effectiveness results. Results: Compared with first or second generation TKI, osimertinib had a base-case incremental costeffectiveness ratio (ICER) of SG$418,839 (US$304,277) per quality-adjusted life year gained. One-way sensitivity analysis showed the ICER was most sensitive to time horizon and variations in progressionfree utility values. Scenario analyses showed that a 50% reduction in the cost of osimertinib was still associated with a high ICER that was unlikely to be deemed cost effective. Conclusions: Osimertinib is not cost effective as a first-line treatment compared to standard EGFR TKIs in advanced EGFR mutant NSCLC patients in Singapore. The findings from our evaluation, alongside other considerations including the lack of survival benefit in the Asian subgroup of the FLAURA trial, will be useful to inform policy makers on funding decisions for NSCLC treatments in Singapore.

Cost-effectiveness of osimertinib versus standard EGFR-TKI as first-line treatment for EGFR-mutated advanced non-small-cell lung cancer in China

“…Nevertheless, the ICER is already very close to the WTP of China in our study, indicating appropriate price reduction may make osimertinib cost-effective. Our results are in accordance with economic evaluations in other countries comparing first-line osimertinib, gefitinib, or afatinib in advanced EGFR-mutated NSCLC, which may help clinicians and administrators determine the preferred economic treatment strategy ( Aziz et al, 2020 ; Khoo and Gao, 2021 ).…”

“…However, the acceptable cost-effectiveness could be significantly improved when the cost of osimertinib was reduced by 25%, which was consistent with our results and those of Aguiar et al (2018) . Similarly, the ICER values of SG$418,839/QALY and A$432,197/QALY for osimertinib vs. first-generation EGFR-TKIs in first-line therapy with advanced EGFR-mutant NSCLC in Singapore and Australia were obtained, respectively, which was higher than the then WTP (SG$100,000/QALY and A$50,000/QALY, respectively), revealing to be not cost-effective ( Aziz et al, 2020 ; Khoo and Gao, 2021 ). Another Markov analysis published in Spain indicated a similar cost-effectiveness as compared to first-generation EGFR-TKI because ICER (€273,895.36/QALY) was higher than the commonly accepted threshold €24,000/QALY of Spain while a discount of more than 60% was a cost-effective option ( Aguilar-Serra et al, 2019 ).…”

“…Frontiers in Pharmacology frontiersin.org line osimertinib, gefitinib, or afatinib in advanced EGFR-mutated NSCLC, which may help clinicians and administrators determine the preferred economic treatment strategy (Aziz et al, 2020;Khoo and Gao, 2021).…”

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

“…The results of the economic evaluations were used to directly support decisions regarding reimbursement via HTA documents ( n = 20) [ 69 – 88 ]. For the remainder, studies stated that the use was for policy/funding decisions ( n = 5) [ 34 , 35 , 48 , 56 , 62 ], to promote the sustainability of limited healthcare resources ( n = 5) [ 30 – 32 , 60 , 61 ], or to support treatment choices ( n = 7) [ 39 , 47 , 50 , 55 , 57 , 59 , 65 ]. Twenty-two studies did not explicitly state the intended use of the economic evaluations [ 33 , 36 – 38 , 40 – 46 , 49 , 51 – 54 , 58 , 63 , 64 , 66 – 68 ].…”

Prognosis of different bone metastases patterns in EGFR-mutant advanced lung adenocarcinoma patients

“…However, EGFR-TKI as rst-line treatment has multiple treatment options in real-world setting (Hayashi et al 2022;How et al 2022), and treatment decisions mainly depend on the characteristics of tumors and the feasibility based on patient-related factors, particularly with regards to cost-effectiveness in clinical practice. Pharmacoeconomic studies suggest that rst-line rst-generation EGFR-TKI and gene-guided osimertinib second-line strategy was more cost-effective than osimertinib rst-line treatment (Ezeife et al 2018;Aziz et al 2020; Khoo et al 2021;Cai et al 2019). In addition, APPLE trial (Remon et al 2023) updated data and showed comparable OS between rst-line osimertinib versus ge tinib followed by osimertinib in European Lung Cancer Congress 2023.…”