Impact of epidermal growth factor receptor (EGFR) activating mutations and their targeted treatment in the prognosis of stage IV non-small cell lung cancer (NSCLC) patients harboring liver metastasis

• Published in: Journal of translational medicine Vol. 13; no. 1; p. 257
• Main Authors: Castañón, Eduardo, Rolfo, Christian, Viñal, David, López, Inés, Fusco, Juan P, Santisteban, Marta, Martin, Patricia, Zubiri, Leire, Echeveste, José I, Gil-Bazo, Ignacio
• Format: Journal Article
• Language: English
• Published: England BioMed Central 07-08-2015
• Subjects: Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - pathology; Humans; Liver Neoplasms - secondary; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Mutation - genetics; Neoplasm Staging; Prognosis; Receptor, Epidermal Growth Factor - genetics; Survival Analysis
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/s12967-015-0622-x

Liver metastases appear in 20-30% of patients diagnosed with non-small cell lung cancer (NSCLC) and represent a poor prognosis feature of NSCLC and a possibly more treatment-resistant condition. Potential clinical outcome differences in NSCLC patients with liver metastases harboring molecular alterations in EGFR, KRAS and EML4-ALK genes are still to be determined. This study aims to evaluate the incidence of liver metastasis in a single population and look for potential correlations between EGFR mutations, liver infiltration and clinical outcomes.
A total of 236 consecutive stage IV NSCLC patients treated at the Clínica Universidad de Navarra were analyzed.
At onset, liver metastases were present in 16.9% of patients conferring them a shorter overall survival (OS) compared to those with different metastatic locations excluding liver infiltration (10 vs. 21 months; p = 0.001). Patients with EGFR wild-type tumors receiving standard chemotherapy and showing no liver involvement presented a superior median OS compared to those with liver metastases (23 vs. 13 months; p = 0.001). Conversely, patients with EGFR-mutated tumors treated with EGFR tyrosin-kinase inhibitors (TKI's) presented no significant differences in OS regardless of liver involvement (median OS not reached vs. 25 months; p = 0.81).
Overall, liver metastases at onset negatively impact OS of NSCLC patients. EGFR TKIs however, may reverse the effects of an initial negative prognosis of liver metastasis in first-line treatment of EGFR mutated NSCLC patients.