Afatinib for the treatment of metastatic non-small cell lung cancer

Monika Joshi, Syed M. Rizvi, Chandra P. Belani

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Targeting the epidermal growth factor receptor (EGFR) in patients with non small cell lung cancer (NSCLC) harboring sensitizing mutations in the tyrosine kinase (TKI) domain has led to a significant change in the management of this disease. The classic or sensitizing mutations are G719X mutation in exon 18, in-frame deletions or insertion of exon 19, L858R or L861Q mutation in exon 21. Approximately 90% of these mutations are exon 19 deletion or exon 21 L858R point mutation. Gefitinib and erlotinib are reversible first-generation inhibitors of mutant EGFR, and treatment with these agents in the first-line setting has demonstrated a progression-free survival of 9.5–13.7 months. However, the majority of these patients ultimately develop resistance to these drugs. Afatinib is an irreversible pan-ErbB inhibitor that was developed to circumvent the problem of resistance to first-generation TKIs. The LUX-Lung studies have evaluated the efficacy and toxicities of afatinib in treatment-naïve and refractory NSCLC patients. The promising results of some of these trials led to approval of afatinib by the US Food and Drug Administration for patients with advanced NSCLC and EGFR  exon 19 deletions or exon 21 (L858R) substitution mutations. Afatinib causes toxicities similar to those of the first-generation EGFR TKIs, such as diarrhea, rash, acne, and stomatitis, and overall is well tolerated. This article focuses on the clinical studies of afatinib in patients with NSCLC.

Original languageEnglish (US)
Pages (from-to)75-82
Number of pages8
JournalCancer Management and Research
Volume7
DOIs
StatePublished - Jan 1 2015

Fingerprint

Non-Small Cell Lung Carcinoma
Exons
Epidermal Growth Factor Receptor
Mutation
Therapeutics
Stomatitis
Acne Vulgaris
United States Food and Drug Administration
Disease Management
BIBW 2992
Exanthema
Point Mutation
Drug Resistance
Protein-Tyrosine Kinases
Disease-Free Survival
Diarrhea
Lung

Keywords

  • Afatinib
  • Epidermal growth factor receptor
  • Non-small cell lung cancer
  • Tyrosine kinase inhibitor

ASJC Scopus subject areas

  • Oncology

Cite this

Afatinib for the treatment of metastatic non-small cell lung cancer. / Joshi, Monika; Rizvi, Syed M.; Belani, Chandra P.

In: Cancer Management and Research, Vol. 7, 01.01.2015, p. 75-82.

Research output: Contribution to journalArticle

@article{696976374cf3463f9ba27ea91932f8a2,
title = "Afatinib for the treatment of metastatic non-small cell lung cancer",
abstract = "Targeting the epidermal growth factor receptor (EGFR) in patients with non small cell lung cancer (NSCLC) harboring sensitizing mutations in the tyrosine kinase (TKI) domain has led to a significant change in the management of this disease. The classic or sensitizing mutations are G719X mutation in exon 18, in-frame deletions or insertion of exon 19, L858R or L861Q mutation in exon 21. Approximately 90{\%} of these mutations are exon 19 deletion or exon 21 L858R point mutation. Gefitinib and erlotinib are reversible first-generation inhibitors of mutant EGFR, and treatment with these agents in the first-line setting has demonstrated a progression-free survival of 9.5–13.7 months. However, the majority of these patients ultimately develop resistance to these drugs. Afatinib is an irreversible pan-ErbB inhibitor that was developed to circumvent the problem of resistance to first-generation TKIs. The LUX-Lung studies have evaluated the efficacy and toxicities of afatinib in treatment-na{\"i}ve and refractory NSCLC patients. The promising results of some of these trials led to approval of afatinib by the US Food and Drug Administration for patients with advanced NSCLC and EGFR  exon 19 deletions or exon 21 (L858R) substitution mutations. Afatinib causes toxicities similar to those of the first-generation EGFR TKIs, such as diarrhea, rash, acne, and stomatitis, and overall is well tolerated. This article focuses on the clinical studies of afatinib in patients with NSCLC.",
keywords = "Afatinib, Epidermal growth factor receptor, Non-small cell lung cancer, Tyrosine kinase inhibitor",
author = "Monika Joshi and Rizvi, {Syed M.} and Belani, {Chandra P.}",
year = "2015",
month = "1",
day = "1",
doi = "10.2147/CMAR.S51808",
language = "English (US)",
volume = "7",
pages = "75--82",
journal = "Cancer Management and Research",
issn = "1179-1322",
publisher = "Dove Medical Press Ltd.",

}

TY - JOUR

T1 - Afatinib for the treatment of metastatic non-small cell lung cancer

AU - Joshi, Monika

AU - Rizvi, Syed M.

AU - Belani, Chandra P.

PY - 2015/1/1

Y1 - 2015/1/1

N2 - Targeting the epidermal growth factor receptor (EGFR) in patients with non small cell lung cancer (NSCLC) harboring sensitizing mutations in the tyrosine kinase (TKI) domain has led to a significant change in the management of this disease. The classic or sensitizing mutations are G719X mutation in exon 18, in-frame deletions or insertion of exon 19, L858R or L861Q mutation in exon 21. Approximately 90% of these mutations are exon 19 deletion or exon 21 L858R point mutation. Gefitinib and erlotinib are reversible first-generation inhibitors of mutant EGFR, and treatment with these agents in the first-line setting has demonstrated a progression-free survival of 9.5–13.7 months. However, the majority of these patients ultimately develop resistance to these drugs. Afatinib is an irreversible pan-ErbB inhibitor that was developed to circumvent the problem of resistance to first-generation TKIs. The LUX-Lung studies have evaluated the efficacy and toxicities of afatinib in treatment-naïve and refractory NSCLC patients. The promising results of some of these trials led to approval of afatinib by the US Food and Drug Administration for patients with advanced NSCLC and EGFR  exon 19 deletions or exon 21 (L858R) substitution mutations. Afatinib causes toxicities similar to those of the first-generation EGFR TKIs, such as diarrhea, rash, acne, and stomatitis, and overall is well tolerated. This article focuses on the clinical studies of afatinib in patients with NSCLC.

AB - Targeting the epidermal growth factor receptor (EGFR) in patients with non small cell lung cancer (NSCLC) harboring sensitizing mutations in the tyrosine kinase (TKI) domain has led to a significant change in the management of this disease. The classic or sensitizing mutations are G719X mutation in exon 18, in-frame deletions or insertion of exon 19, L858R or L861Q mutation in exon 21. Approximately 90% of these mutations are exon 19 deletion or exon 21 L858R point mutation. Gefitinib and erlotinib are reversible first-generation inhibitors of mutant EGFR, and treatment with these agents in the first-line setting has demonstrated a progression-free survival of 9.5–13.7 months. However, the majority of these patients ultimately develop resistance to these drugs. Afatinib is an irreversible pan-ErbB inhibitor that was developed to circumvent the problem of resistance to first-generation TKIs. The LUX-Lung studies have evaluated the efficacy and toxicities of afatinib in treatment-naïve and refractory NSCLC patients. The promising results of some of these trials led to approval of afatinib by the US Food and Drug Administration for patients with advanced NSCLC and EGFR  exon 19 deletions or exon 21 (L858R) substitution mutations. Afatinib causes toxicities similar to those of the first-generation EGFR TKIs, such as diarrhea, rash, acne, and stomatitis, and overall is well tolerated. This article focuses on the clinical studies of afatinib in patients with NSCLC.

KW - Afatinib

KW - Epidermal growth factor receptor

KW - Non-small cell lung cancer

KW - Tyrosine kinase inhibitor

UR - http://www.scopus.com/inward/record.url?scp=84923247267&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84923247267&partnerID=8YFLogxK

U2 - 10.2147/CMAR.S51808

DO - 10.2147/CMAR.S51808

M3 - Article

C2 - 25733926

AN - SCOPUS:84923247267

VL - 7

SP - 75

EP - 82

JO - Cancer Management and Research

JF - Cancer Management and Research

SN - 1179-1322

ER -