The comparison of outcomes from tyrosine kinase inhibitor monotherapy in second- or third-line for advanced non-small-cell lung cancer patients with wild-type or unknown EGFR status

• Published in: Oncotarget 2016-06, Vol.7 (24), p.35803-35812
• Main Authors: Bronte, Giuseppe, Franchina, Tindara, Alù, Massimiliano, Sortino, Giovanni, Celesia, Claudia, Passiglia, Francesco, Savio, Giuseppina, Laudani, Agata, Russo, Alessandro, Picone, Antonio, Rizzo, Sergio, De Tursi, Michele, Gambale, Elisabetta, Bazan, Viviana, Natoli, Clara, Blasi, Livio, Adamo, Vincenzo, Russo, Antonio
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Erlotinib Hydrochloride - therapeutic use; Female; Humans; Kaplan-Meier Estimate; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Male; Middle Aged; Mutation; Protein Kinase Inhibitors - therapeutic use; Quinazolines - therapeutic use; Receptor, Epidermal Growth Factor - genetics; Research Paper; Retrospective Studies; Treatment Outcome
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.8130

Second-line treatment for advanced non-small-cell lung cancer (NSCLC) patients includes monotherapy with a third-generation cytotoxic drug (CT) or a tyrosine kinase inhibitor (TKI). These options are the actual standard for EGFR wild-type (WT) status, as patients with EGFR mutations achieve greater benefit by the use of TKI in first-line treatment. Some clinical trials and meta-analyses investigated the comparison between CT and TKI in second-line, but data are conflicting. We designed a retrospective trial to gather information about TKI sensitivity in comparison with CT. We selected from clinical records patients treated with at least 1 line of CT and at least 1 line of TKI. We collected data about age, sex, performance status, comorbidity, smoking status, histotype, metastatic sites, EGFR status, treatment schedule, better response and time-to-progression (TTP) for each line of treatment and overall survival (OS). 93 patients met selection criteria. Mean age 66,7 (range: 46-84). M/F ratio is 3:1. 39 EGFR-WT and 54 EGFR-UK. All patients received erlotinib or gefitinib as second-line treatment or erlotinib as third-line treatment. No TTP differences were observed for both second-line (HR:0,91; p = 0,6333) and third-line (HR:1.1; p = 0,6951) treatment (TKI vs CT). A trend of a benefit in OS in favor of 3rd-line TKI (HR:0,68; p = 0,11). This study explores the role of TKIs in EGFR non-mutated NSCLC patients. OS analysis highlights a trend to a benefit in patients who received TKI in third-line, even if this result is statistically non-significant. Further analysis are needed to find an explanation for this observation.