Clinical features and treatment outcome of non-small cell lung cancer (NSCLC) patients with uncommon or complex epidermal growth factor receptor (EGFR) mutations
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// Stefano Frega 1, 6, * , Martina Lorenzi 1, * , Matteo Fassan 2 , Stefano Indraccolo 3 , Fiorella Calabrese 4 , Adolfo Favaretto 5 , Laura Bonanno 6 , Valentina Polo 1, 6 , Giulia Zago 6 , Francesca Lunardi 4 , Ilaria Attili 1, 6 , Alberto Pavan 1, 6 , Massimo Rugge 2 , Valentina Guarneri 1, 6 , PierFranco Conte 1, 6 , Giulia Pasello 6 1 Department of Surgical, Oncological and Gastroenterological Sciences, University of Padova, Padova, Italy 2 Department of Medicine, Surgical Pathology Unit, University of Padova, Padova, Italy 3 Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto IRCCS, Padova, Italy 4 Department of Cardio-Thoracic and Vascular Sciences, University of Padova, Padova, Italy 5 Medical Oncology, Azienda ULSS 9, Treviso, Italy 6 Medical Oncology 2, Istituto Oncologico Veneto, IRCCS, Padova, Italy * These authors contributed equally to this work Correspondence to: Giulia Pasello, email: giulia.pasello@ioveneto.it 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 ABSTRACT 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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Exon 18 mutations are associated with male sex and smoking history.
“an association with the male sex [18] and smoking history has been reported [19,31]”
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- Authors
- Frega, S., Lorenzi, M., Fassan, M., Indraccolo, S., Calabrese, F., Favaretto, A., Bonanno, L., Polo, V., Zago, G., Lunardi, F., Attili, I., Pavan, A., Rugge, M., Guarneri, V., Conte, P., & Pasello, G.
- Affiliations
- University of Padua (IT)
- Istituto Oncologico Veneto (IT)
- AULSS 2 Marca Trevigiana (IT)
- Corresponding author
- Frega, Stefano
- Lorenzi, Martina
- ORCID
- Venue
- Oncotarget
- Publisher
- Impact Journals, LLC
- Published
- 2017-03-06
- Volume
- 8
- Issue
- 20
- Pages
- 32626-32638
- ISSN
- 1949-2553 (ISSN-L)
- PMC
- PMC5464815
- OpenAlex
- W2592489711
- Cited by
- 17
- References
- 45
- Citations by year
- 2024: 2 · 2023: 1 · 2021: 3 · 2020: 6 · 2019: 4 · 2018: 1
- FWCI
- 2.49
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- cc-by
- Locations
- Oncotarget (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Padua Research Archive (University of Padova) (submittedVersion)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
- Keywords
- non-small cell lung cancer, EGFR mutation, uncommon EGFR mutations, tyrosine kinase inhibitors, first-line therapy, progression-free survival, overall survival, EGFR exon 19 deletion, EGFR exon 21 L858R, EGFR exon 20 insertion
- MeSH terms
- Aged, Aged, 80 and over, Carcinoma, Non-Small-Cell Lung, Female, Humans, Lung Neoplasms, Male, Middle Aged, Mutation, Retrospective Studies, Treatment Outcome, Protein Kinase Inhibitors, ErbB Receptors
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