Phase II, open-label trial to assess the effect of continuous oral afatinib (BIBW 2992) at a daily dose of 50 mg on QTc, pharmacokinetics, and efficacy in relapsed or refractory solid tumors including brain metastases and glioblastoma that is not amenable to other therapy.

2613^ Background: Afatinib (BIBW 2992) is an oral, irreversible ErbB family blocker. This trial prospectively evaluated the possible proarrhythmic potential of afatinib by assessing QTc interval, as well as its PK and clinical efficacy. Methods: Patients (pts) with tumors known to overexpress EGFR or HER2, including those with brain metastases and GBM were eligible for treatment with daily afatinib 50mg. Pts with a QTcF-interval >470 ms, a PR-interval >230 ms, a QRS-interval >120 ms and ST-segment and T/U-wave abnormalities at screening, as assessed by central cardiology review, were excluded. 60 pts were treated. Time-matched 24-h ECGs were performed prior to drug exposure, after single dose and at steady state. Pharmacokinetic (PK) samples were drawn on days coincident with ECGs. Results: 49 of 60 pts were analyzed for the QTcF. The largest mean time matched QTcF change from baseline to Day 14 was 1.6 ms (90% CI –2.1, 5.2) at 1 h post dosing. The analysis of the relationship between the afatinib concent...