Serum protein level as a predictor of therapeutic response and adverse effects associated with afatinib use.

Background: Afatinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor with significant serum protein binding. Total protein level was found to be associated with plasma afatinib level. The trough serum concentration was shown to be associated with development of adverse effects. This study aims to explore the association between serum protein levels and clinical responses and adverse effects in advanced stage non-small cell lung cancer (NSCLC) treated with afatinib.

Methods: This was a retrospective cohort study of Chinese patients with metastatic NSCLC harboring mutations who received first or second line afatinib treatment. The association of serum protein and album levels, as well as their ratio, and the development of adverse effects was investigated.

Results: Among 217 patients included, 91 were on afatinib as first line treatment and 126 as second line treatment. Higher serum protein levels, albumin levels and albumin to globulin ratio, were found to be associated with clinical response to afatinib among patients on first or second line setting. Among patients on first line afatinib with Eastern Cooperative Oncology Group Performance State (ECOG PS) at 1 or above, those with lower serum protein levels at baseline had higher risks of developing grade 2 or above gastrointestinal adverse effects. Among patients on second line afatinib and with ECOG PS at 1 or above, patients with lower serum protein levels at baseline had higher risks of developing grade 3 or above cutaneous adverse effects. Lower serum albumin to globulin ratio at baseline was associated with increased risks of grade 3 or above gastrointestinal adverse effects among patients with ECOG PS at 1 or above and no prior systemic chemotherapy.

Conclusions: Serum protein, albumin level and serum albumin to globulin ratio may predict the response to afatinib and occurrence of adverse effects with afatinib treatment.