Once-daily oral afatinib (A) combined with pemetrexed (P) in patients (pts) with advanced solid tumors: A phase I dose escalation trial.

e13011 Background: A is an oral, irreversible, ErbB Family Blocker with single-agent activity in a variety of solid tumors. Preclinical studies have demonstrated additive antitumor effects when combining A or erlotinib with P in non-small cell lung cancer cell lines with sensitizing or resistant EGFR mutations. We hypothesized that once-daily A given with P would be safe and feasible in pts with advanced solid tumors. Methods: This Phase I trial was a standard 3+3 dose escalation design where A was administered orally at a starting dose of 30 mg/day on days 2–21 and combined with IV P (500 mg/m2) on Day 1 of a 21-day cycle. A was increased by 10 mg for each successive cohort until determination of the MTD, defined as the dose of A below which ≥2 of six pts experienced dose-limiting toxicity (DLT) in Cycle 1. MTD cohort was expanded to 18 pts and incidence and severity of AEs were graded according to CTCAE v3.0. Pts were treated to a maximum of 6 cycles with the option for A monotherapy thereafter. Results...