Cancer Res Treat.  2019 Apr;51(2):502-509. 10.4143/crt.2018.117.

Efficacy and Safety of Afatinib for EGFR-mutant Non-small Cell Lung Cancer, Compared with Gefitinib or Erlotinib

Affiliations
  • 1Division of Hematology-Oncology, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. jongmu.sun@skku.edu

Abstract

PURPOSE
We tried to evaluate whether there are any specific features in treatment outcomes of firstline afatinib in patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC), compared with gefitinib or erlotinib.
MATERIALS AND METHODS
We analyzed patients treated with first-line afatinib, gefitinib, or erlotinib for advanced EGFR-mutant NSCLC at Samsung Medical Center between 2014 and 2016.
RESULTS
In total, 467 patients received first-line afatinib (n=165), gefitinib (n=230), or erlotinib (n=72). Afatinib was used more often in patients with tumors harboring deletion in exon 19 (Del19), whereas the gefitinib group had more elderly, females, and never smokers. The median progression-free survival (PFS) time for afatinib, gefitinib, and erlotinib was 19.1 months, 13.7 months, and 14.0 months, respectively (p=0.001). The superior PFS of afatinib was more remarkable in subgroups of Del19 or uncommon EGFR mutations. Overall toxicity profiles of the three drugs were comparable, though more grade 3 or 4 toxicities were detected in afatinib (7.3%) compared with gefitinib (2.6%) or erlotinib (1.8%). The common grade 3 or 4 toxicities of afatinib included diarrhea (3.0%), paronychia (2.4%), and skin rash (1.8%). Dose modification was more frequently required in patients treated with afatinib (112/165, 68%), compared with gefitinib (5/230, 2%) and erlotinib (4/72, 6%). Interestingly, however, dose reduction in the afatinib group did not impair its efficacy in terms of PFS (dose reduction vs. no reduction group, 23.5 months vs. 12.4 months).
CONCLUSION
First-line afatinib showed satisfactory efficacy data and manageable toxicity profiles.

Keyword

Afatinib; First-line therapy; Epidermal growth factor receptor; Non-small cell lung carcinoma

MeSH Terms

Aged
Carcinoma, Non-Small-Cell Lung*
Diarrhea
Disease-Free Survival
Erlotinib Hydrochloride*
Exanthema
Exons
Female
Humans
Paronychia
Receptor, Epidermal Growth Factor
Erlotinib Hydrochloride
Receptor, Epidermal Growth Factor

Figure

  • Fig. 1. Progression-free survival (A) and overall survival (B) with afatinib, gefitinib, and erlotinib. TKI, tyrosine kinase inhibitor.

  • Fig. 2. Progression-free survival of afatinib, gefitinib, and erlotinib according to epidermal growth factor receptor (EGFR) mutation types. (A) Exon 19 deletion. (B) Exon 21 L858R. (C) Uncommon EGFR mutations. TKI, tyrosine kinase inhibitor.


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