Phase II study of dasatinib in the treatment of head and neck squamous cell carcinoma (HNSCC)

Abstract

6022 Background: Dasatinib is a potent inhibitor of src-family kinases, ephA2, PDGFR, Abl, and c-kit. A single-center, open-label, phase II trial was conducted to evaluate the safety, tolerability, pharmacokinetics (PK), and efficacy of dasatinib in recurrent or metastatic HNSCC. Methods: Pts with measurable disease by RECIST, who received 0 or 1 prior regimen for recurrent or metastatic HNSCC with an ECOG performance status 0–1 and tumor tissue appropriate for IHC and FISH were eligible. Dasatinib 100 mg bid was given for 28-day cycles. Primary endpoints were 12-wk progression-free survival (PFS) and objective response rate (ORR). Pts who took at least 1 dose of dasatinib and who died or left study before 12 wks were counted as progressive disease (PD). A 2 stage design, closure after accrual of 15 pts was required if PFS was 45% or less and ORR was 0. Otherwise, planned accrual was 35. Response was assessed at 4 and 12 wks. PK was studied in pts receiving dasatinib per PEG. Biomarkers relevant to Src pathway were planned in tissue and blood. Results: Fifteen pts were accrued. To date, 13 pts are evaluable for response, and 15 pts for toxicity. No grade 3/4 hematologic toxicities were noted. Grade 2–4 nonhematologic toxicities(n): pleural effusion(2), nausea/vomiting(2), dehydration(1), diarrhea(1), dyspnea(1). Toxicity led to hospitalization of 4 pts and drug discontinuation in 5 pts. ORR was 0. One pt was stable at 12 wks (PFS: 7.6%). This pt stopped drug at 15 wks due to toxicity, but also had PD. One pt died on study and cause was deemed unlikely related. Conclusions: Dosed at 100mg bid, dasatinib led to a characteristic toxicity profile in this pt population. Rates of hospitalization and discontinuation for toxicity were fairly high. Final efficacy parameters are pending evaluation of 2 pts. Evaluation of PK and tissue/blood biomarkers is ongoing. No significant financial relationships to disclose.