A phase II study of lapatinib (GW572016) in recurrent/metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN)

Abstract

5568 Background: Epidermal growth factor receptor (EGFR) inhibitors have demonstrated reproducible activity in patients with R/M SCCHN. HER2 is the preferred dimerization partner for EGFR. Lapatinib is a dual EGFR and HER2 kinase inhibitor that has demonstrated promising preclinical activity in SCCHN models. Methods: This phase II multi-institutional study enrolls patients with R/M SCCHN into 2 cohorts: those without prior exposure to an EGFR inhibitor (arm A) and those with prior exposure to an EGFR inhibitor (arm B). All subjects were treated with lapatinib 1500mg OD. Primary endpoints were response rate (arm A) and progression-free survival (arm B). Results: 42 subjects have been enrolled (27 arm A, 15 arm B; 35 male, 7 female, median age 60 years). Toxicity was generally mild without any dose reductions or patient withdrawal due to adverse effects. Diarrhea was the most frequent toxicity occurring in 40% of patients. Other toxicities observed included fatigue (21%), rash (21%) and nausea (14%). 2 patients experienced grade 3 toxicity (1 diarrhea, 1 emesis). 1 patient had a reduction in left ventricular ejection fraction (60% to 40%) which was asymptomatic and recovered to baseline upon discontinuation of lapatinib. No objective responses were observed in either arm. In an intent-to-treat analysis stable disease was the best response observed in 37% of arm A and 20% of arm B subjects. Median PFS was 1.6 months in arm A and 1.7 months in arm B. Conclusions: Lapatinib as a single agent in R/M SCCHN, although well tolerated, appears to have little activity in either EGFR inhibitor naïve or refractory subjects. No significant financial relationships to disclose.