Phase II, open-label trial to assess QTcF effects, pharmacokinetics and antitumor activity of afatinib in patients with relapsed or refractory solid tumors

Cancer Chemother Pharmacol. 2013 Dec;72(6):1213-22. doi: 10.1007/s00280-013-2286-7. Epub 2013 Oct 2.


Purpose: Afatinib is an irreversible ErbB family blocker currently under evaluation in late-stage clinical trials. This study primarily assessed the cardiac safety, pharmacokinetics and antitumor activity of afatinib in cancer patients.

Methods: In this multicenter, Phase II, open-label, single-arm trial, 60 patients with solid tumors who were expected to express epidermal growth factor receptor-1 and HER2 received oral afatinib 50 mg daily. QTcF intervals (QT interval corrected by the Fridericia formula) were evaluated based on electrocardiogram recordings time-matched with pharmacokinetic blood samples after single (Day 1) and continuous (Day 14; steady state) administration. Adverse events were classified according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 3.0; antitumor activity was assessed using RECIST 1.0.

Results: There was a nonsignificant decrease of 0.3 ms (90 % confidence interval -2.8, 2.3; N = 49) in the mean of the average time-matched QTcF interval from baseline to steady state. The maximum plasma concentration for afatinib was seen at median tmax 3 h after both single dose and at steady state. No relationship between afatinib plasma concentrations and time-matched QTcF, QT and heart rate change was found. The overall adverse event profile was consistent with the known safety profile of afatinib. One patient demonstrated a partial response (PR) and two patients unconfirmed PRs.

Conclusions: Afatinib had no impact on cardiac repolarization, had a manageable safety profile and demonstrated antitumor activity in this uncontrolled study.

Publication types

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

MeSH terms

  • Administration, Oral
  • Afatinib
  • Aged
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Electrocardiography
  • ErbB Receptors / metabolism*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoplasms / drug therapy*
  • Neoplasms / pathology
  • Quinazolines / administration & dosage
  • Quinazolines / adverse effects
  • Quinazolines / therapeutic use*
  • Receptor, ErbB-2 / metabolism*
  • Treatment Outcome


  • Antineoplastic Agents
  • Quinazolines
  • Afatinib
  • ERBB2 protein, human
  • ErbB Receptors
  • Receptor, ErbB-2