Risk of elevated transaminases in non-small cell lung cancer (NSCLC) patients treated with erlotinib, gefitinib and afatinib: a meta-analysis

ABSTRACT

This meta-analysis has been conducted to determine the risk of elevated transaminases associated with the use of erlotinib, gefitinib and afatinib in patients with non-small cell lung cancer (NSCLC). Studies eligible for our analysis included randomized phase II and III trials of patients with NSCLC on the three agents which describe events of elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Initial database search revealed 300 relevant citations. After excluding non-eligible studies, 24 trials were considered eligible for the analysis. The relative risk (RR) of all-grade elevated ALT and AST was 1.82 (95% CI: 1.42–2.34; p < 0.00001) and 2.09 (95% CI: 1.54–2.83; p < 0.00001) respectively; while for high-grade elevated ALT and AST, it was 9.23 (95% CI: 5.06–16.85; p < 0.00001) and 1.78 (95% CI: 0.5–6.26; p = 0.37), respectively. Our meta-analysis has shown that there is an overall elevated risk of elevated transaminases with the use of these agents.

KEYWORDS:

• Erlotinib
• gefitinib
• afatinib
• ALT
• AST

Financial & competing interests disclosure

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Key issues

Background:

• This meta-analysis has been conducted to determine the risk of elevated transaminases associated with the use of erlotinib, gefitinib and afatinib in patients with non-small cell lung cancer (NSCLC).

Methodology:

• Studies eligible for our analysis included randomized phase II and III trials of patients with NSCLC on the three agents which describe events of elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST).

Results:

• Initial database search revealed 300 relevant citations.

• After excluding non-eligible studies, 24 trials were considered eligible for the analysis.

• The relative risk (RR) of all-grade elevated ALT and AST was 1.82 (95% CI: 1.42–2.34; p < 0.00001) and 2.09 (95% CI: 1.54–2.83; p < 0.00001), respectively.

• While for high-grade elevated ALT and AST, the RR was 9.23 (95% CI: 5.06–16.85; p < 0.00001) and 1.78 (95% CI: 0.5–6.26; p = 0.37), respectively.

• Thus, our meta-analysis has shown that there is an overall elevated risk of elevated transaminases with the use of these agents.

• Clinicians should pay proper attention when administering these agents.