Abstract
BackgroundThe 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.MethodsWe 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.ResultsSeventeen 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.ConclusionsALK-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.
Highlights
The anaplastic lymphoma kinase tyrosine kinase inhibitors (ALK-TKIs) have been administered to patients with Anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer for a long period of time and show a promising response.the differences in the toxicity profiles among these drugs are still unclear
The frequency of severe adverse events (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
Statistically significant differences in some severe AEs among ceritinib, crizotinib and alectinib were detected in present study
Summary
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.the differences in the toxicity profiles among these drugs are still unclear. 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. With the discovery of anaplastic lymphoma kinase (ALK) rearrangements, small-molecule ALK tyrosine kinase inhibitors (TKIs) become the most active therapeutic areas of study in ALK-positive non-small-cell lung cancer (NSCLC) patients. State Key Laboratory of Oncology in Southern China, Collaborative. Full list of author information is available at the end of the article of brain metastases were the biggest obstacles during the treatment of crizotinib in ALK-positive NSCLC. Generation ALK TKIs (ceritinib and alectinib) came into our sight and approved by the United States (US) Food and Drug Administration (FDA) for treated patients with crizotinib-intolerant, crizotinib-progressive or crizotinib-resistant ALK-positive NSCLC
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