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Updated: Feb 28, 2026
Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
Published on: September 18, 2013
Pooled safety analyses of ALK-TKI inhibitor in ALK-positive NSCLC
Qian Zhu1,2, Hao Hu3, De-Sheng Weng1,2
1State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People's Republic of China.
Background:
The anaplastic lymphoma kinase tyrosine kinase inhibitors (ALK-TKIs) have been administered to patients with ALK-positive non-small cell lung cancer for a long period of time and show a promising response. However, the differences in the toxicity profiles among these drugs are still unclear.
Methods:
We performed a comprehensive search of the MEDLINE, EMBASE, WEB OF SCIENCE and COCHRANE databases from the drugs' inception to May 2016 to identify clinical trials. Severe adverse events (AEs) (grade ≥ 3) based on the ALK-TKI type were analysed.
Results:
Seventeen trials published between 2011 and 2016, including a total of 1826 patients, were eligible for analysis. Patients in 10 trials (n = 1000) received crizotinib, patients in 5 trials (n = 601) received ceritinib and patients in 2 trials (n = 225) received alectinib. The overall frequencies of treatment-related death and AEs due to treatment withdrawal were 0.9% (12/1365) and 5.5% (85/1543), respectively. Moreover, the frequency of severe AEs in patients treated with ceritinib was significantly higher than patients treated with crizotinib or alectinib, especially for hepatotoxicity, fatigue and some of gastrointestinal symptoms. Additionally, significant difference in the elevated lipase and amylase levels (grade ≥ 3) were detected between ceritinib and crizotinib/alectinib, whereas neutropenia was less frequent.
Conclusions:
ALK-TKIs were safe for ALK-positive patients. Moreover, statistically significant differences in some severe AEs among ceritinib, crizotinib and alectinib were detected in present study.
Insights
Anaplastic lymphoma kinase tyrosine kinase inhibitors (ALK-TKIs) are safe for non-small cell lung cancer patients. However, ceritinib showed higher severe adverse events compared to crizotinib and alectinib.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Anaplastic lymphoma kinase tyrosine kinase inhibitors (ALK-TKIs) are used for ALK-positive non-small cell lung cancer.
- The comparative toxicity profiles of different ALK-TKIs are not well-understood.
Purpose of the Study:
- To compare the severe adverse events (AEs) of different ALK-TKIs in patients with ALK-positive non-small cell lung cancer.
Main Methods:
- A comprehensive literature search was conducted across major databases (MEDLINE, EMBASE, Web of Science, Cochrane) up to May 2016.
- Clinical trials reporting severe AEs (grade ≥ 3) were analyzed based on ALK-TKI type.
Main Results:
- Seventeen trials with 1826 patients were included, receiving crizotinib, ceritinib, or alectinib.
- Overall treatment-related death was 0.9% and AEs leading to withdrawal were 5.5%.
- Ceritinib showed significantly higher severe AEs (hepatotoxicity, fatigue, gastrointestinal symptoms) compared to crizotinib and alectinib; neutropenia was less frequent.
Conclusions:
- ALK-TKIs are generally safe for ALK-positive non-small cell lung cancer patients.
- Significant differences in severe AEs exist among ceritinib, crizotinib, and alectinib.
