Re-challenge of afatinib after 1st generation EGFR-TKI failure in patients with previously treated non-small cell lung cancer harboring EGFR mutation

Cancer Chemother Pharmacol. 2019 May;83(5):817-825. doi: 10.1007/s00280-019-03790-w. Epub 2019 Feb 13.

Abstract

Background: Re-challenge of erlotinib after gefitinib failure is reported to yield some benefit in patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutation. However, little is known about the re-challenge of afatinib after 1st generate on EGFR tyrosine kinase inhibitor (TKI) failure.

Methods: From May 2015 to August 2018, 62 patients with advanced NSCLC harboring sensitive EGFR mutation received afatinib after gefitinib and/or erlotinib failure at our institution was included in our retrospective study.

Results: The overall response rate (ORR) and disease control rate (DCR) of afatinib as re-challenge were 17.0% and 79.2%, respectively. The median time on treatment of 1st generation EGFR-TKI (1st TKI) was 14 months. By multivariate analysis, smoking, performance status (PS), and time on treatment of 1st TKI with more than 10 months were confirmed to be independent prognostic factors predicting a worse progression-free survival (PFS), and significant prognostic markers for overall survival (OS) were PS and time on treatment of 1st TKI with more than 10 months, especially in patients with exon 19 deletion.

Conclusions: Re-challenge of afatinib was identified as one of the therapeutic options after 1st TKI failure in the patients with advanced NSCLC harboring EGFR mutation when the time of treatment by prior 1st TKI is more than 10 months.

Keywords: Afatinib; EGFR mutation; EGFR-TKI; Re-challenge.

MeSH terms

  • Adult
  • Afatinib / administration & dosage*
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / administration & dosage*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology
  • ErbB Receptors / genetics
  • Erlotinib Hydrochloride / administration & dosage
  • Female
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Mutation
  • Protein Kinase Inhibitors / administration & dosage*
  • Retrospective Studies
  • Treatment Failure
  • Treatment Outcome

Substances

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