Efficacy and Safety of Re-administration of Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor (EGFR-TKI) After EGFR-TKI-Induced Interstitial Lung Disease (CS-Lung-005)

Lung. 2024 Feb;202(1):63-72. doi: 10.1007/s00408-023-00669-9. Epub 2024 Jan 24.

Abstract

Purpose: This study investigated the safety and efficacy of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) re-administration after recovery from EGFR-TKI-induced interstitial lung disease (ILD).

Methods: This multicenter retrospective study collected data from consecutive advanced NSCLC patients who underwent EGFR-TKI re-administration after recovery from EGFR-TKI-induced ILD.

Results: Fifty-eight patients were registered. The grades of initial TKI-induced ILD were grade 1 to 4. TKIs used for re-administration were erlotinib for 15 patients, osimertinib for 15, gefitinib for 14, afatinib for 13 patients, and dacomitinib for 1 patient. ILD recurred in 13 patients (22.4%), comprising 3 patients with grade 1, 6 patients with grade 2, and 4 patients with grade 3. No significant associations were found between ILD recurrence and age, smoking history, performance status, time from initial ILD to TKI re-administration, or concomitant corticosteroid use. However, the incidence of ILD recurrence was high in cases of repeated use of gefitinib or erlotinib or first time use of osimertinib at TKI re-administration. The ILD recurrence rate was lowest in patients treated with first time use of gefitinib (8%) or erlotinib (8%), followed by patients treated with repeated use of osimertinib (9%). The response rate, median progression-free survival by TKI re-administration, and median overall survival were 55%, 9.6 and 84.8 months, respectively.

Conclusion: This study showed that EGFR-TKI re-administration is a feasible and effective treatment for patients who recovered from EGFR-TKI-induced ILD. Our results indicate that re-administration of EGFR-TKI is an important option for long-term prognosis after recovery from EGFR-TKI-induced ILD.

Keywords: Epidermal growth factor inhibitor; Interstitial lung disease; Pneumonitis; Rechallenge; Response rate; Survival.

Publication types

  • Multicenter Study

MeSH terms

  • Acrylamides
  • Aniline Compounds
  • Antineoplastic Agents* / adverse effects
  • ErbB Receptors / antagonists & inhibitors
  • Erlotinib Hydrochloride / adverse effects
  • Gefitinib / adverse effects
  • Humans
  • Indoles
  • Lung
  • Lung Diseases, Interstitial* / chemically induced
  • Lung Neoplasms* / drug therapy
  • Pyrimidines
  • Retrospective Studies
  • Tyrosine Kinase Inhibitors* / adverse effects
  • Tyrosine Kinase Inhibitors* / therapeutic use

Substances

  • Acrylamides
  • Aniline Compounds
  • Antineoplastic Agents
  • EGFR protein, human
  • ErbB Receptors
  • Erlotinib Hydrochloride
  • Gefitinib
  • Indoles
  • osimertinib
  • Pyrimidines
  • Tyrosine Kinase Inhibitors