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

被引:30
作者
Joshi, Monika [1 ]
Rizvi, Syed M. [1 ]
Belani, Chandra P. [1 ]
机构
[1] Penn State Milton S Hershey Med Ctr, Dept Med, Div Hematol Oncol, Hershey, PA USA
关键词
afatinib; non-small cell lung cancer; epidermal growth factor receptor; tyrosine kinase inhibitor; GROWTH-FACTOR RECEPTOR; PHASE-III TRIAL; OPEN-LABEL; 1ST-LINE TREATMENT; EGFR MUTATIONS; BIBW; 2992; ACQUIRED-RESISTANCE; GENE-MUTATIONS; GEFITINIB; ERLOTINIB;
D O I
10.2147/CMAR.S51808
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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-naive 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.
引用
收藏
页码:75 / 82
页数:8
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