Afatinib in EGFR TKI-naïve patients with locally advanced or metastatic EGFR mutation-positive non-small cell lung cancer: Interim analysis of a Phase 3b study

Lung Cancer. 2021 Feb;152:127-134. doi: 10.1016/j.lungcan.2020.12.011. Epub 2020 Dec 17.

Abstract

Objectives: Randomized controlled trials have demonstrated that afatinib is a suitable treatment option for patients with epidermal growth factor receptor mutation-positive (EGFRm +) non-small cell lung cancer (NSCLC). However, such studies often exclude patients treated in routine clinical practice. We report interim results from a Phase 3b, open-label, multicenter, single-arm, exploratory trial, in which afatinib was investigated in a real-world setting.

Materials and methods: Patients with EGFRm + tyrosine kinase inhibitor (TKI)-naïve NSCLC received afatinib 40 mg orally, once-daily, until disease progression, or voluntary withdrawal. Primary objective was safety.

Results: Overall, 479 patients received afatinib: median age 65 years, 8 % of patients had an ECOG performance status ≥ 2, 17 % had brain metastases, and 13 % had tumors containing uncommon mutations only. All but one patient (99.8 %) had an adverse event (AE). Treatment-related AEs (TRAEs; any/grade ≥ 3) occurred in 97 %/44 % of patients; most common were diarrhea (87 %/16 %) and rash (51 %/11 %). AEs leading to afatinib dose-reduction were reported in 258 patients (54 %), and 37 patients (8 %) discontinued treatment due to a TRAE. Objective response rate was 45.5 %, median duration of response was 14.1 months (95 % CI: 12.2-16.4). Overall median time to symptomatic progression and progression-free survival were 14.9 months (95 % CI: 13.8-17.6) and 13.4 months (95 % CI: 11.8-14.5), respectively, in the overall population and 19.3 months (95 % CI: 15.6-21.8) and 15.9 months (95 % CI: 13.9-19.1) in patients with EGFR exon 19 deletions.

Conclusions: Afatinib administration in routine clinical practice was well tolerated with no new safety signals and demonstrated promising efficacy in patients with EGFRm + NSCLC. TRAEs were generally manageable with tolerability-guided dose reductions. Overall, these data independently support findings from randomized controlled trials of afatinib in EGFRm + NSCLC.

Keywords: Afatinib; EGFR TKI-naïve; EGFR mutation; NSCLC; Safety.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Afatinib / therapeutic use
  • Aged
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • ErbB Receptors / genetics
  • Humans
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / genetics
  • Mutation
  • Protein Kinase Inhibitors / therapeutic use
  • Treatment Outcome

Substances

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