Impaired Liver Function Implied Shorter Progression Free Survival for EGFR Tyrosine Kinase Inhibitors

Area of Science:

• Oncology
• Pharmacology
• Hepatology

Background:

• Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKI) are standard for advanced non-small cell lung cancer (NSCLC) with EGFR mutations.
• Liver toxicity, specifically elevated transaminases, is a dose-limiting factor for TKIs but often overlooked.
• The clinical significance of transaminase elevation in relation to treatment efficacy requires further investigation.

Purpose of the Study:

• To explore the relationship between transaminase elevation and progression-free survival (PFS) in advanced NSCLC patients treated with EGFR TKI.
• To assess the impact of alanine aminotransferase (ALT) and aspartate transaminase (AST) levels on treatment outcomes.

Main Methods:

• Retrospective study of treatment-naïve advanced NSCLC patients with sensitive EGFR mutations receiving EGFR TKI.
• Recorded highest ALT and AST levels during treatment.
• Analyzed correlation between transaminase levels and PFS using Cox regression.

Main Results:

• 208 patients were included; gefitinib was the most common TKI (48.6%).
• Median PFS for the cohort was 11.2 months.
• 35.1% of patients experienced elevated transaminases, with ALT elevation in 31.3% and AST in 11.5%.
• Elevated ALT levels were associated with significantly shorter PFS (9.5 months vs. 12.6 months for normal ALT, P=0.025).
• AST elevation did not show a significant relationship with PFS (P=0.259).

Conclusions:

• Elevated ALT levels during EGFR TKI therapy are inversely related to PFS in advanced NSCLC patients.
• Liver impairment from EGFR TKI treatment, particularly ALT elevation, should be closely monitored.
• These findings suggest that transaminase levels may serve as a predictive or prognostic marker in EGFR TKI therapy.