Efficacy and safety of first-line afatinib in older patients with advanced EGFR-mutated non-small cell lung cancer

Korean J Intern Med. 2025 Jul;40(4):626-633. doi: 10.3904/kjim.2024.269. Epub 2025 Jul 1.

Abstract

Background/aims: This study investigated the efficacy and safety of first-line afatinib treatment in older patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC).

Methods: This retrospective, multicenter, observational cohort study included 103 patients aged ≥ 75 years who were treated with first-line afatinib for EGFR-mutated NSCLC. The primary outcome was time-on-treatment (TOT).

Results: The median TOT of patients was 13.6 months (95% confidence interval 11.0-16.2). Ninety-two patients (89.3%) required dose modification. Dose reduction was significantly more frequent in the 40 mg starting dose group than in the 30 mg group (93.1% vs. 68.8%, p = 0.004). The most common grade 3 or worse adverse events (AEs) were diarrhea (n = 16, 54%), acneiform rash (n = 4, 14.3%), and stomatitis (n = 4, 14.3%). Grade 3 or worse AEs led to dose modification in 23 of 28 patients (82.1%) and permanent discontinuation of therapy in five of 28 patients (17.9%). On disease progression, tissue re-biopsy was performed in 18 of 74 patients (24.3%). Thirty-four patients (45.9%) received subsequent chemotherapy; of these, most patients (n = 21, 61.8%) received pemetrexed monotherapy.

Conclusion: This study demonstrated the efficacy of first-line afatinib treatment for EGFR-mutant NSCLC in older patients. However, despite similar safety profiles and frequencies of AEs reported in previous studies, the frequency of dose modifications was higher in this population. A 30 mg starting dose of afatinib and a predefined dose adjustment may be suitable strategies for this population. Post-tyrosine kinase inhibitor management, such as tissue re-biopsy and platinum-based chemotherapy, tended to be underprescribed in this age group.

Keywords: Afatinib; Aged; Lung neoplasms; Safety; Treatment outcome.

Publication types

  • Multicenter Study
  • Observational Study

MeSH terms

  • Afatinib* / administration & dosage
  • Afatinib* / adverse effects
  • Afatinib* / therapeutic use
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents* / administration & dosage
  • Antineoplastic Agents* / adverse effects
  • Antineoplastic Agents* / therapeutic use
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / enzymology
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Carcinoma, Non-Small-Cell Lung* / mortality
  • Carcinoma, Non-Small-Cell Lung* / pathology
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / genetics
  • Female
  • Humans
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / enzymology
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / mortality
  • Lung Neoplasms* / pathology
  • Male
  • Mutation*
  • Protein Kinase Inhibitors* / administration & dosage
  • Protein Kinase Inhibitors* / adverse effects
  • Protein Kinase Inhibitors* / therapeutic use
  • Retrospective Studies
  • Time Factors
  • Treatment Outcome

Substances

  • Afatinib
  • ErbB Receptors
  • EGFR protein, human
  • Protein Kinase Inhibitors
  • Antineoplastic Agents