Phase 2 study of intermittent pulse dacomitinib in patients with advanced non-small cell lung cancers

•Intermittent pulse dacomitinib is safe and tolerated well.•Pharmacokinetic analysis suggest similar drug exposures to daily dose dacomitinib.•No evidence of cardiac adverse events with pulse dosing in this study.•Pulse dacomitinib was not effective in patients with lung cancers with EGFR T790M.

BackgroundDacomitinib is a second-generation, irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI). Pre-clinical data suggest that intermittent pulsatile dosing of dacomitinib may result in inhibition of EGFR T790M.MethodsWe evaluated safety, pharmacokinetics and efficacy of intermittent pulsatile dacomitinib in both molecularly unselected patients and patients with lung cancers harboring EGFR T790M (Clinical Trial Registration Number NCT01858389).ResultsThirty-eight patients were treated on study with pulse dacomitinib; sixteen with EGFR T790M in Cohort A and 22 who were not molecularly selected in Cohort B. One patient out of 16 patients in Cohort A had a partial response to study therapy (ORR 6.3%, 95% CI 0.2-30.2%). The median progression-free survival (PFS) in Cohort A was 2.3 months and median PFS in Cohort B was 1.6 months. The adverse event profile was similar to standard daily dose dacomitinib with the most frequent treatment-related toxicities occurring in >20% of patients being diarrhea, rash, stomatitis, nausea, dry skin, paronychia, fatigue, and decreased appetite.ConclusionIntermittent pulsatile dacomitinib is safe and relatively well tolerated but is not effective in patients that harbor EGFR T790M or in unselected patients with non-small cell lung cancer.