Alma D Campos-Parra1, Carlos Zuloaga, María Eugenia Vazquez Manríquez, Alejandro Avilés, Jose Borbolla-Escoboza, Andrés Cardona, Abelardo Meneses, Oscar Arrieta. 1. *Laboratory of Experimental Oncology †Thoracic Oncology Clinic §Department of Pathology #Laboratory of Translational Medicine, Instituto Nacional de Cancerología (INCan) ‡Department of Pathology, Instituto Nacional de Enfermedades Respiratorias (INER), Tlalpan, México, D.F ∥Boehringer Ingelheim, Barrio Xaltocan, Xochimilco, México City, México ¶Clinical and Translational Oncology Group, Institute of Oncology, Fundación Santa Fe de Bogotá, Bogotá, Colombia.
Abstract
OBJETIVE: In patients with non-small cell lung cancer (NSCLC), knowledge of the epidermal growth factor receptor (EGFR) mutation status is fundamental for selecting the treatment involving EGFR-tyrosine kinase inhibitors (EGFR-TKIs). Little information is available regarding the response and progression-free survival (PFS) in platinum-based chemotherapy (CT) versus EGFR-TKIs in the presence or absence of KRAS mutation, particularly in patients without EGFR mutation. METHODS: From 2007 to 2010, 353 patients with NSCLC were treated with first-line CT, EGFR-TKIs were used in the second or third line of treatment. Tests were performed for EGFR and KRAS mutation and the results of the mutations were obtained 3 to 4 months after the start of the treatment. We analyzed clinical characteristics, mutation profile, response and PFS to CT and EGFR-TKIs, and overall survival. The protocol is registered with ClinicalTrials.gov, number NCT01023828. RESULTS: Presence of the wild-type (WT) KRAS was independently associated with increased response rate to first-line CT when compared with KRAS mutation (41.4% vs. 14.7%; P=0.001). The EGFR mutation (57.8% vs. 11.7%; P<0.001) and WT-KRAS (39.6% vs. 3.3%; P=0.001) were associated with the EGFR-TKIs response. PFS of patients with WT-EGFR and KRAS mutation treated with EGFR-TKIs was shorter when compared with patients with WT-EGFR and WT-KRAS (P<0.001). CONCLUSIONS: KRAS mutation status is a good biomarker for response to EGFR-TKIs in patients with NSCLC. KRAS mutational status could impact the decision to give CT or EGFR-TKIs as a second line of treatment to patients with NSCLC, particularly in patients with WT-EGFR.
OBJETIVE: In patients with non-small cell lung cancer (NSCLC), knowledge of the epidermal growth factor receptor (EGFR) mutation status is fundamental for selecting the treatment involving EGFR-tyrosine kinase inhibitors (EGFR-TKIs). Little information is available regarding the response and progression-free survival (PFS) in platinum-based chemotherapy (CT) versus EGFR-TKIs in the presence or absence of KRAS mutation, particularly in patients without EGFR mutation. METHODS: From 2007 to 2010, 353 patients with NSCLC were treated with first-line CT, EGFR-TKIs were used in the second or third line of treatment. Tests were performed for EGFR and KRAS mutation and the results of the mutations were obtained 3 to 4 months after the start of the treatment. We analyzed clinical characteristics, mutation profile, response and PFS to CT and EGFR-TKIs, and overall survival. The protocol is registered with ClinicalTrials.gov, number NCT01023828. RESULTS: Presence of the wild-type (WT) KRAS was independently associated with increased response rate to first-line CT when compared with KRAS mutation (41.4% vs. 14.7%; P=0.001). The EGFR mutation (57.8% vs. 11.7%; P<0.001) and WT-KRAS (39.6% vs. 3.3%; P=0.001) were associated with the EGFR-TKIs response. PFS of patients with WT-EGFR and KRAS mutation treated with EGFR-TKIs was shorter when compared with patients with WT-EGFR and WT-KRAS (P<0.001). CONCLUSIONS: KRAS mutation status is a good biomarker for response to EGFR-TKIs in patients with NSCLC. KRAS mutational status could impact the decision to give CT or EGFR-TKIs as a second line of treatment to patients with NSCLC, particularly in patients with WT-EGFR.
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