Impact of Exon 19 Deletion Subtypes in EGFR-Mutant Metastatic Non–Small-Cell Lung Cancer Treated With First-Line Tyrosine Kinase Inhibitors

Sabrina Rossi, Luca Toschi, Giovanna Finocchiaro, Vincenzo Di Noia, Maria Bonomi, Eleonora Cerchiaro, Giovanni Luca Ceresoli, Giordano Domenico Beretta, Ettore D'Argento, Armando Santoro

Research output: Contribution to journalArticle

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Abstract

Background: Common epidermal growth factor receptor (EGFR) mutations in non–small-cell lung cancer (NSCLC) predict sensitivity to EGFR tyrosine kinase inhibitors (TKIs), with exon 19 deletions being associated with better outcome compared to L858R mutations. We aimed to investigate the impact of different exon 19 deletions on patient outcome in EGFR-mutant NSCLC treated with first-line TKIs. Patients and Methods: In this retrospective analysis, 106 patients with metastatic NSCLC harboring EGFR exon 19 deletions and treated with first-line TKIs were included. The primary end point was overall survival (OS), the secondary end point progression-free survival (PFS). Analyses were performed by grouping exon 19 deletions according to 2 models: we compared different type of deletion (delE746_A750 vs. deletions other than delE746-A750, defined as “uncommon”) or different starting codon of deletion (E746 vs. L747). Results: The frequency of uncommon deletions of exon 19 was 36%. When delE746_A750 (n = 68) was compared to the other deletions in exon 19 (n = 38), no differences were found, either in terms of OS (P = .65) or PFS (P = .65). Similarly, no difference in OS (P = .74) or PFS (P = .99) emerged when comparing the E746 group (n = 81) to the L747 group (n = 25). On multivariate analysis including clinical characteristics and type of deletions (delE746_A750 vs. uncommon deletions or E746 vs. L747), only the presence of brain metastases at diagnosis or during TKI treatment was associated with shorter PFS but not with worse OS. Conclusion: Different exon 19 deletions are equally sensitive to first-line EGFR-TKIs in EGFR-mutant NSCLC. Patients affected by oncogene-addicted metastatic non–small-cell lung cancer harboring the uncommon epidermal growth factor receptor (EGFR) mutation seem to have similar survival outcomes compared to those with common EGFR mutations and have disease that responds either to gefitinib or afatinib.

Original languageEnglish
JournalClinical Lung Cancer
DOIs
Publication statusAccepted/In press - Jan 1 2018

Fingerprint

Epidermal Growth Factor Receptor
Non-Small Cell Lung Carcinoma
Protein-Tyrosine Kinases
Exons
Disease-Free Survival
Survival
Mutation
Oncogenes
Codon
Multivariate Analysis
Neoplasm Metastasis
Brain

Keywords

  • Afatinib
  • Codon
  • Gefitinib
  • NSCLC
  • TKIs

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

Cite this

Impact of Exon 19 Deletion Subtypes in EGFR-Mutant Metastatic Non–Small-Cell Lung Cancer Treated With First-Line Tyrosine Kinase Inhibitors. / Rossi, Sabrina; Toschi, Luca; Finocchiaro, Giovanna; Di Noia, Vincenzo; Bonomi, Maria; Cerchiaro, Eleonora; Ceresoli, Giovanni Luca; Beretta, Giordano Domenico; D'Argento, Ettore; Santoro, Armando.

In: Clinical Lung Cancer, 01.01.2018.

Research output: Contribution to journalArticle

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title = "Impact of Exon 19 Deletion Subtypes in EGFR-Mutant Metastatic Non–Small-Cell Lung Cancer Treated With First-Line Tyrosine Kinase Inhibitors",
abstract = "Background: Common epidermal growth factor receptor (EGFR) mutations in non–small-cell lung cancer (NSCLC) predict sensitivity to EGFR tyrosine kinase inhibitors (TKIs), with exon 19 deletions being associated with better outcome compared to L858R mutations. We aimed to investigate the impact of different exon 19 deletions on patient outcome in EGFR-mutant NSCLC treated with first-line TKIs. Patients and Methods: In this retrospective analysis, 106 patients with metastatic NSCLC harboring EGFR exon 19 deletions and treated with first-line TKIs were included. The primary end point was overall survival (OS), the secondary end point progression-free survival (PFS). Analyses were performed by grouping exon 19 deletions according to 2 models: we compared different type of deletion (delE746_A750 vs. deletions other than delE746-A750, defined as “uncommon”) or different starting codon of deletion (E746 vs. L747). Results: The frequency of uncommon deletions of exon 19 was 36{\%}. When delE746_A750 (n = 68) was compared to the other deletions in exon 19 (n = 38), no differences were found, either in terms of OS (P = .65) or PFS (P = .65). Similarly, no difference in OS (P = .74) or PFS (P = .99) emerged when comparing the E746 group (n = 81) to the L747 group (n = 25). On multivariate analysis including clinical characteristics and type of deletions (delE746_A750 vs. uncommon deletions or E746 vs. L747), only the presence of brain metastases at diagnosis or during TKI treatment was associated with shorter PFS but not with worse OS. Conclusion: Different exon 19 deletions are equally sensitive to first-line EGFR-TKIs in EGFR-mutant NSCLC. Patients affected by oncogene-addicted metastatic non–small-cell lung cancer harboring the uncommon epidermal growth factor receptor (EGFR) mutation seem to have similar survival outcomes compared to those with common EGFR mutations and have disease that responds either to gefitinib or afatinib.",
keywords = "Afatinib, Codon, Gefitinib, NSCLC, TKIs",
author = "Sabrina Rossi and Luca Toschi and Giovanna Finocchiaro and {Di Noia}, Vincenzo and Maria Bonomi and Eleonora Cerchiaro and Ceresoli, {Giovanni Luca} and Beretta, {Giordano Domenico} and Ettore D'Argento and Armando Santoro",
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T1 - Impact of Exon 19 Deletion Subtypes in EGFR-Mutant Metastatic Non–Small-Cell Lung Cancer Treated With First-Line Tyrosine Kinase Inhibitors

AU - Rossi, Sabrina

AU - Toschi, Luca

AU - Finocchiaro, Giovanna

AU - Di Noia, Vincenzo

AU - Bonomi, Maria

AU - Cerchiaro, Eleonora

AU - Ceresoli, Giovanni Luca

AU - Beretta, Giordano Domenico

AU - D'Argento, Ettore

AU - Santoro, Armando

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Background: Common epidermal growth factor receptor (EGFR) mutations in non–small-cell lung cancer (NSCLC) predict sensitivity to EGFR tyrosine kinase inhibitors (TKIs), with exon 19 deletions being associated with better outcome compared to L858R mutations. We aimed to investigate the impact of different exon 19 deletions on patient outcome in EGFR-mutant NSCLC treated with first-line TKIs. Patients and Methods: In this retrospective analysis, 106 patients with metastatic NSCLC harboring EGFR exon 19 deletions and treated with first-line TKIs were included. The primary end point was overall survival (OS), the secondary end point progression-free survival (PFS). Analyses were performed by grouping exon 19 deletions according to 2 models: we compared different type of deletion (delE746_A750 vs. deletions other than delE746-A750, defined as “uncommon”) or different starting codon of deletion (E746 vs. L747). Results: The frequency of uncommon deletions of exon 19 was 36%. When delE746_A750 (n = 68) was compared to the other deletions in exon 19 (n = 38), no differences were found, either in terms of OS (P = .65) or PFS (P = .65). Similarly, no difference in OS (P = .74) or PFS (P = .99) emerged when comparing the E746 group (n = 81) to the L747 group (n = 25). On multivariate analysis including clinical characteristics and type of deletions (delE746_A750 vs. uncommon deletions or E746 vs. L747), only the presence of brain metastases at diagnosis or during TKI treatment was associated with shorter PFS but not with worse OS. Conclusion: Different exon 19 deletions are equally sensitive to first-line EGFR-TKIs in EGFR-mutant NSCLC. Patients affected by oncogene-addicted metastatic non–small-cell lung cancer harboring the uncommon epidermal growth factor receptor (EGFR) mutation seem to have similar survival outcomes compared to those with common EGFR mutations and have disease that responds either to gefitinib or afatinib.

AB - Background: Common epidermal growth factor receptor (EGFR) mutations in non–small-cell lung cancer (NSCLC) predict sensitivity to EGFR tyrosine kinase inhibitors (TKIs), with exon 19 deletions being associated with better outcome compared to L858R mutations. We aimed to investigate the impact of different exon 19 deletions on patient outcome in EGFR-mutant NSCLC treated with first-line TKIs. Patients and Methods: In this retrospective analysis, 106 patients with metastatic NSCLC harboring EGFR exon 19 deletions and treated with first-line TKIs were included. The primary end point was overall survival (OS), the secondary end point progression-free survival (PFS). Analyses were performed by grouping exon 19 deletions according to 2 models: we compared different type of deletion (delE746_A750 vs. deletions other than delE746-A750, defined as “uncommon”) or different starting codon of deletion (E746 vs. L747). Results: The frequency of uncommon deletions of exon 19 was 36%. When delE746_A750 (n = 68) was compared to the other deletions in exon 19 (n = 38), no differences were found, either in terms of OS (P = .65) or PFS (P = .65). Similarly, no difference in OS (P = .74) or PFS (P = .99) emerged when comparing the E746 group (n = 81) to the L747 group (n = 25). On multivariate analysis including clinical characteristics and type of deletions (delE746_A750 vs. uncommon deletions or E746 vs. L747), only the presence of brain metastases at diagnosis or during TKI treatment was associated with shorter PFS but not with worse OS. Conclusion: Different exon 19 deletions are equally sensitive to first-line EGFR-TKIs in EGFR-mutant NSCLC. Patients affected by oncogene-addicted metastatic non–small-cell lung cancer harboring the uncommon epidermal growth factor receptor (EGFR) mutation seem to have similar survival outcomes compared to those with common EGFR mutations and have disease that responds either to gefitinib or afatinib.

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