Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) for non-small cell lung cancer

Roza S, Balqis AG, Sit Wai L, Izzuna MMG
Record ID 32018005472
Authors' objectives: (i) To assess the comparative effectiveness and safety of ALK tyrosine kinase inhibitors given as monotheraphy to treat patients with advanced and metastatic ALK positive NSCLC (ii) To determine the economic, organizational, social, ethical and legal implications of ALK tyrosine kinase inhibitors given as monotheraphy to treat patients with advanced and metastatic ALK positive NSCLC
Authors' results and conclusions: Overall ALK inhibitors appeared beneficial in improving in PFS, OS, ORR, intracranial ORR and HRQoL compared to chemotherapy or crizotinib in patients with advanced ALK positive NSCLC at first or further line of treatment setting. Next generation ALK inhibitors including ceritinib, alectinib, lorlatinib offered greater clinical benefit with superior PFS, ORR compared to crizotinib (as the first line treatment) in patients with advanced ALK positive NSCLC). Next generation ALK inhibitor including alectinib, lorlatinib, brigatinib were demonstrated to be superior in OS, PFS, ORR, intracranial ORR, and HRQoL compared with chemotherapy or crizotinib in patients with advanced ALK positive NSCLC in the further line of treatment. ALK inhibitors appeared safe with acceptable safety profile. CEA conducted in various countries from payer and provider perspective demonstrated that the ICER varies. Ceritinib offered a cost-effective option compared to crizotinib or chemotherapy in Hong Kong and Canada. Alectinib offered a cost-effective option in the US as the first line treatment in patients with advanced ALK positive NSCLC. For patients with metastatic non-squamous NSCLC, a minimum of these biomarkers (EGFR mutation, ALK fusion, BRAF mutation, ROS1 fusion, and PD-L1 expression level) should be tested at properly accredited laboratories. Many international guidelines recommended ALK inhibitors to be used in the treatment of advanced patients with NSCLC. From the economic evaluation, ICER for the newer generation ALK TKI; ceritinib, alectinib and lorlatinib were all higher than cost-effectiveness threshold of one GDP per capita per QALY gained for Malaysia. Among these three ALK TKIs, ceritinib and alectinib were found to be more cost-effective compared to lorlatinib. The one-way sensitivity analysis indicated that the annual discounting rate, progression free state utility values and cost of the newer generation ALK TKI have shown to be sensitive parameter for ICER and may be a key determinant before considering the first line treatment for advanced non-small cell lung cancer for the ALK gene mutation patients. It was also found that reduction of drug price demonstrated a significant reduction of ICER.
Authors' recommendations: Based on the above review, ALK inhibitors (ceritinib, alectinib, lorlatinib) offer greater clinical benefit and acceptable safety profile compared to chemotherapy or crizotinib in patients with advanced ALK positive NSCLC. In view of the current therapeutic gap, ceritinib may be used as a standard treatment option for patients with advanced and metastatic ALK positive NSCLC. Alectinib should be considered in advanced ALK positive NSCLC patients who have progressed after treatment with ALK inhibitors other than crizotinib, or patients intolerant to ceritinib or crizotinib. To meet the treatment needs, competitive price or appropriate drug assistance policies should be provided.
Authors' methods: The following electronic databases were searched through the Ovid interface: Ovid MEDLINE® and Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Daily and Versions® 1946 to September 2022, EBM Reviews - Health Technology Assessment (3 rd Quarter 2022), EBM Reviews - Cochrane Database of Systematic Review (2005 to September 2022), EBM Reviews - Cochrane Central Register of Controlled Trials (September 2022), and EBM Reviews - NHS Economic Evaluation Database (3 rd Quarter 2022). Parallel searches were run in PubMed, US FDA and INAHTA database. Search was limited to articles in English and in human. The last search was performed on 10th February 2022. Additional articles were identified from reviewing the references of retrieved articles. A state transition model (Markov cohort simulation) was developed to compare the cost-effectiveness of two treatment strategies based on the suggestion from the clinical experts. The model structure was constructed with reference to the published studies and in consultation with experts. Three health states namely progression free state (PFS), progressed disease state (PD) and dead (D) as the absorption state were included in the model. The inputs of transition probabilities were derived from the literatures. The costs used in this analysis were based on MalaysianDRG Casemix Costing, published literatures and input from Pharmaceutical Services Program, Ministry of Health. The analyses were conducted from the perspective of Ministry of Health Malaysia and projected to lifetime horizon with one month transition cycle. Deterministic sensitivity analysis was performed as one-way sensitivity analysis to assess the model’s robustness toward change in parameters.
Authors' identified further research: -
Project Status: Completed
Year Published: 2022
Requestor: Decision-making committee
English language abstract: An English language summary is available
Publication Type: Full HTA
Country: Malaysia
MeSH Terms
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms
  • Anaplastic Lymphoma Kinase
  • Crizotinib
  • Protein Kinase Inhibitors
  • Tyrosine Kinase Inhibitors
  • Anaplastic Lymphoma Kinase (ALK); Tyrosine Kinase Inhibitor (TKI); Non-Small Cell Lung Cancer
Organisation Name: Malaysian Health Technology Assessment
Contact Address: Malaysian Health Technology Assessment Section, Ministry of Health Malaysia, Federal Government Administrative Centre, Level 4, Block E1, Parcel E, 62590 Putrajaya Malaysia Tel: +603 8883 1229
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Copyright: Malaysian Health Technology Assessment Section (MaHTAS)
This is a bibliographic record of a published health technology assessment from a member of INAHTA or other HTA producer. No evaluation of the quality of this assessment has been made for the HTA database.