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Author Spotlight: Advancements in Molecular Biomarker Testing for Non-Squamous Non-Small Cell Lung Cancer
Published on: September 8, 2023
A comprehensive clinical evaluation of first-line drugs for ALK-positive advanced non-small cell lung cancer
Wan-Qing Wang1, Tao Xu1, Jing-Jing Zhang1
1Department of Pharmacy, The First Affiliated Hospital of Soochow University, Suzhou, China.
Background:
Anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKIs) are mainly used in the treatment of ALK-positive advanced non-small cell lung cancer (NSCLC), but a comprehensive clinical evaluation of ALK-TKIs is lacking. Hence, a comparison of ALK-TKIs for first-line treatment of ALK-positive advanced NSCLC is essential to provide rational drug use and a basis for improving national policies and systems.
Methods:
According to the Guideline for the Administration of Clinical Comprehensive Evaluation of Drugs (2021) and the Technical Guideline for the Clinical Comprehensive Evaluation of Antitumor Drugs (2022), a comprehensive clinical evaluation index system of first-line treatment drugs for ALK-positive advanced NSCLC was established by literature review and expert interviews. We conducted a systematic literature review, meta-analysis, and other relevant data analyses, combined with an indicator system, to establish a quantitative and qualitative integration analysis for each indicator and each dimension of crizotinib, ceritinib, alectinib, ensartinib, brigatinib, and lorlatinib.
Results:
The comprehensive clinical evaluation results of all dimensions were as follows: in terms of safety, alectinib had a lower incidence of grade 3 and above adverse reactions; for effectiveness, alectinib, brigatinib, ensartinib, and lorlatinib showed better clinical efficacy, and alectinib and brigatinib have been recommended by several clinical guidelines; in terms of economy, second-generation ALK-TKIs have more cost-utility advantages, and both alectinib and ceritinib have been recommended by the UK and Canadian Health Technology Assessment (HTA) agencies; for suitability, accessibility, and innovation, alectinib has a higher degree of physician recommendations and patient compliance. Except for brigatinib and lorlatinib, all other ALK-TKIs have been admitted to the medical insurance directory; the accessibility of crizotinib, ceritinib, and alectinib is good, meeting the needs of patients. Second- and third-generation ALK-TKIs have higher blood-brain barrier permeability, stronger inhibition ability, and innovation than first-generation ALK-TKIs.
Conclusions:
Compared with other ALK-TKIs, alectinib performs better across six dimensions and has a higher comprehensive clinical value. The results provide better drug choice and rational use for patients with ALK-positive advanced NSCLC.
Insights
Alectinib demonstrates superior overall clinical value among anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKIs) for treating advanced non-small cell lung cancer (NSCLC). This comprehensive evaluation aids in optimizing treatment choices for ALK-positive NSCLC patients.
Area of Science:
- Oncology
- Pharmacology
- Clinical Medicine
Background:
- Anaplastic lymphoma kinase-tyrosine kinase inhibitors (ALK-TKIs) are critical for ALK-positive advanced non-small cell lung cancer (NSCLC).
- A comprehensive clinical evaluation comparing first-line ALK-TKIs is currently lacking.
- This study aims to provide a basis for rational drug use and policy improvement in ALK-positive advanced NSCLC treatment.
Purpose of the Study:
- To conduct a comprehensive clinical evaluation of first-line ALK-TKIs for ALK-positive advanced NSCLC.
- To compare crizotinib, ceritinib, alectinib, ensartinib, brigatinib, and lorlatinib across multiple dimensions.
- To establish a quantitative and qualitative integration analysis for rational drug selection and policy development.
Main Methods:
- Established a comprehensive clinical evaluation index system based on literature review and expert interviews.
- Conducted systematic literature review and meta-analysis.
- Performed quantitative and qualitative integration analysis for each ALK-TKI across defined indicators and dimensions.
Main Results:
- Alectinib showed a lower incidence of severe adverse reactions and superior overall clinical value.
- Alectinib, brigatinib, ensartinib, and lorlatinib demonstrated better clinical efficacy; alectinib and brigatinib are guideline-recommended.
- Second-generation ALK-TKIs offer cost-utility advantages; alectinib and ceritinib are recommended by health technology assessment agencies.
Conclusions:
- Alectinib exhibits superior performance across six evaluated dimensions, offering higher comprehensive clinical value for ALK-positive advanced NSCLC.
- The findings support improved drug selection and rational use for patients with ALK-positive advanced NSCLC.
- Second- and third-generation ALK-TKIs generally show enhanced blood-brain barrier permeability, inhibition ability, and innovation compared to first-generation agents.
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