Sequencing of therapy following first-line afatinib in patients with EGFR mutation-positive non-small cell lung cancer

Lung Cancer. 2019 Jun:132:126-131. doi: 10.1016/j.lungcan.2019.04.014. Epub 2019 Apr 10.

Abstract

Objectives: With the availability of several epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs), sequential therapy could potentially render EGFR mutation-positive non-small cell lung cancer a chronic disease in some patients. In this retrospective analysis of EGFR mutation-positive (Del19/L858R) patients receiving first-line afatinib in LUX-Lung 3, 6, and 7, we assessed uptake of, and outcomes following, subsequent therapies including the third-generation EGFR TKI, osimertinib.

Methods: Post-progression therapy data were prospectively collected during follow-up. Molecular testing of tumours at progression/discontinuation of afatinib was not mandatory. Duration of subsequent therapies, and survival following osimertinib, were calculated with Kaplan-Meier estimates.

Results: Among 553 patients who discontinued first-line afatinib, second-, third- and fourth-line therapy was administered in 394 (71%), 265 (48%), and 156 (28%) patients. The most common post-progression therapy was platinum-based chemotherapy (46%). Thirty-seven patients received subsequent osimertinib, 10 as second-line treatment. Median progression-free survival on afatinib in these 37 patients was 21.9 months. Median duration of osimertinib therapy was 20.2 months; median overall survival was not reached after a median follow-up of 4.7 years.

Conclusions: Most patients treated with first-line afatinib received subsequent therapy. Although limited by sample size, enrichment, and a retrospective nature, data from patients who received sequential afatinib and osimertinib are encouraging, warranting further investigation.

Keywords: Afatinib; Non-small cell lung cancer; Osimertinib.

Publication types

  • Clinical Trial, Phase II
  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acrylamides / therapeutic use*
  • Adult
  • Afatinib / therapeutic use*
  • Aged
  • Aged, 80 and over
  • Aniline Compounds / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / mortality
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / genetics
  • Female
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / mortality
  • Male
  • Middle Aged
  • Mutation / genetics
  • Neoplasm Staging
  • Platinum Compounds / therapeutic use*
  • Protein Kinase Inhibitors / therapeutic use*
  • Retrospective Studies
  • Survival Analysis
  • Treatment Outcome

Substances

  • Acrylamides
  • Aniline Compounds
  • Platinum Compounds
  • Protein Kinase Inhibitors
  • osimertinib
  • Afatinib
  • EGFR protein, human
  • ErbB Receptors