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.

// Giuseppe Bronte 1, * , Tindara Franchina 2, * , Massimiliano Alu 3, * , Giovanni Sortino 1 , Claudia Celesia 1 , Francesco Passiglia 1 , Giuseppina Savio 3 , Agata Laudani 3 , Alessandro Russo 2 , Antonio Picone 2 , Sergio Rizzo 1 , Michele De Tursi 4 , Elisabetta Gambale 4 , Viviana Bazan 1 , Clara Natoli 4 , Livio Blasi 3 , Vincenzo Adamo 2 , Antonio Russo 1 1 Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy 2 Medical Oncology Unit-AOOR Papardo-Piemonte, Messina and Department of Human Pathology, University of Messina, Messina, Italy 3 Medical Oncology Unit, A.R.N.A.S. Civico, Palermo, Italy 4 Department of Medical, Oral and Biotechnological Sciences, University “G. D'Annunzio”, Chieti, Italy * These authors contributed equally to this work Correspondence to: Antonio Russo, email: antonio.russo@usa.net Keywords: non-small-cell lung cancer, EGFR, tyrosine kinase inhibitor, chemotherapy Received: January 21, 2016      Accepted: February 28, 2016      Published: March 16, 2016 ABSTRACT Background: 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. Methods: 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). Results: 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). Conclusions: 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.