Research Papers:

Clinical features and treatment outcome of non-small cell lung cancer (NSCLC) patients with uncommon or complex epidermal growth factor receptor (EGFR) mutations

Stefano Frega, Martina Lorenzi, Matteo Fassan, Stefano Indraccolo, Fiorella Calabrese, Adolfo Favaretto, Laura Bonanno, Valentina Polo, Giulia Zago, Francesca Lunardi, Ilaria Attili, Alberto Pavan, Massimo Rugge, Valentina Guarneri, PierFranco Conte and Giulia Pasello _

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Oncotarget. 2017; 8:32626-32638. https://doi.org/10.18632/oncotarget.15945

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Stefano Frega1,6,*, Martina Lorenzi1,*, Matteo Fassan2, Stefano Indraccolo3, Fiorella Calabrese4, Adolfo Favaretto5, Laura Bonanno6, Valentina Polo1,6, Giulia Zago6, Francesca Lunardi4, Ilaria Attili1,6, Alberto Pavan1,6, Massimo Rugge2, Valentina Guarneri1,6, PierFranco Conte1,6, Giulia Pasello6

1Department of Surgical, Oncological and Gastroenterological Sciences, University of Padova, Padova, Italy

2Department of Medicine, Surgical Pathology Unit, University of Padova, Padova, Italy

3Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto IRCCS, Padova, Italy

4Department of Cardio-Thoracic and Vascular Sciences, University of Padova, Padova, Italy

5Medical Oncology, Azienda ULSS 9, Treviso, Italy

6Medical Oncology 2, Istituto Oncologico Veneto, IRCCS, Padova, Italy

*These authors contributed equally to this work

Correspondence to:

Giulia Pasello, email: [email protected]

Keywords: lung cancer, non-small cell, epidermal growth factor receptor, mutations, tyrosine kinase inhibitors

Received: October 28, 2016     Accepted: February 22, 2017     Published: March 06, 2017


Introduction: Tyrosine-kinase inhibitors (TKIs) represent the best treatment for advanced non-small cell lung cancer (NSCLC) with common exon 19 deletion or exon 21 epidermal growth factor receptor mutation (EGFRm). This is an observational study investigating epidemiology, clinical features and treatment outcome of NSCLC cases harbouring rare/complex EGFRm.

Results: Among 764 non-squamous NSCLC cases with known EGFRm status, 26(3.4%) harboured rare/complex EGFRm. Patients receiving first-line TKIs (N = 17) achieved median Progression Free Survival (PFS) and Overall Survival (OS) of 53 (IC 95%, 2–105) and 84 (CI 95%, 27–141) weeks respectively, without significant covariate impact. Response Rate and Disease Control Rate (DCR) were 47% and 65%, respectively. Uncommon exon 19 mutations achieved longer OS and PFS and higher DCR compared with exon 18 and 20 mutations. No additional gene mutation was discovered by MassARRAY analysis. TKIs were globally well tolerated.

Materials and methods: A retrospective review of advanced non-squamous NSCLC harbouring rare/complex EGFRm referred to our Center between 2010 and 2015 was performed. Additional molecular pathways disregulation was explored in selected cases, through MassARRAY analysis.

Conclusions: Peculiar clinical features and lower TKIs sensitivity of uncommon/complex compared with common EGFRm were shown. Exon 19 EGFRm achieved the best TKIs treatment outcome, while the optimal treatment of exon 18 and 20 mutations should be further clarified.

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PII: 15945