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

Document Type: Research Articles

Authors

1 Division of Thoracic Cancer, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.

2 Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, China.

Abstract

Background: Epithelial growth factor receptor tyrosine kinase inhibitor (EGFR TKI) revolutionize the standard
of care for advanced non-small cell lung cancer (NSCLC) harboring sensitive EGFR mutation. Liver toxicity is the
dose-limiting factor for TKI but its importance is largely overlooked. Here the relationship between the elevation
of transaminase and progression-free survival (PFS) was explored. Methods: This was a retrospective study where
patients with advanced NSCLC were screened. And those treatment-naïve and with sensitive EGFR mutation who
were prescribed with EGFR TKI were enrolled. The highest level of transaminase (alanine aminotransferase, ALT, and
aspartate transaminase, AST) during the treatment course was recorded. Results: Totally 208 patients were recruited,
and most of them (48.6%) took gefitinib. The whole cohort achieved a median PFS of 11.2 months (95%CI: 10.0-12.3
m). 73 (35.1%) patients had elevated transaminase and most was attributed to gefitinib (n=43, 42.5%). Specifically,
ALT was elevated in 65 patients (31.3%) while AST in 24 patients (11.5%). Again, gefitinib was associated with more
cases of ALT (40.6%) and AST (17.8%) elevation. The elevation of AST was not related to PFS (P=0.259, HR=0.751,
95%CI: 0.464-1.214). Interestingly, those with normal ALT level had a longer PFS (12.6m, 95%CI: 10.6-14.5 m) than
those with elevated ALT (9.5m 95%CI: 7.9-11.0 m, P=0.025, HR=0.682, 95%CI: 0.488-0.953). The inverse relationship
was confirmed in the COX regression analysis (P=0.047). Conclusion: This study revealed the side effects of elevated
ALT was inversely related to the PFS of EGFR TKI treatment. The liver impairment by TKI should not be overlooked.

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