Research Papers:

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, Tindara Franchina, Massimiliano Alù, Giovanni Sortino, Claudia Celesia, Francesco Passiglia, Giuseppina Savio, Agata Laudani, Alessandro Russo, Antonio Picone, Sergio Rizzo, Michele De Tursi, Elisabetta Gambale, Viviana Bazan, Clara Natoli, Livio Blasi, Vincenzo Adamo and Antonio Russo _

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Oncotarget. 2016; 7:35803-35812. https://doi.org/10.18632/oncotarget.8130

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Giuseppe Bronte1,*, Tindara Franchina2,*, Massimiliano Alù3,*, Giovanni Sortino1, Claudia Celesia1, Francesco Passiglia1, Giuseppina Savio3, Agata Laudani3, Alessandro Russo2, Antonio Picone2, Sergio Rizzo1, Michele De Tursi4, Elisabetta Gambale4, Viviana Bazan1, Clara Natoli4, Livio Blasi3, Vincenzo Adamo2, Antonio Russo1

1Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, Italy

2Medical Oncology Unit-AOOR Papardo-Piemonte, Messina and Department of Human Pathology, University of Messina, Messina, Italy

3Medical Oncology Unit, A.R.N.A.S. Civico, Palermo, Italy

4Department of Medical, Oral and Biotechnological Sciences, University “G. D'Annunzio”, Chieti, Italy

*These authors contributed equally to this work

Correspondence to:

Antonio Russo, email: [email protected]

Keywords: non-small-cell lung cancer, EGFR, tyrosine kinase inhibitor, chemotherapy

Received: January 21, 2016     Accepted: February 28, 2016     Published: March 16, 2016


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.

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