Phase 2 Study of Apatinib, A Novel VEGFR Inhibitor in Patients With Recurrent and/or Metastatic Adenoid Cystic Carcinoma of the Head and Neck: Preliminary Results

Abstract

Recurrent/metastatic adenoid cystic carcinoma (ACC) is an incurable disease with no standard treatments. Apatinib is a tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor 2(VEGFR-2). This study was conducted to assess the efficacy and safety of apatinib in patients with incurable, recurrent/metastatic(R/M) ACC of the head and neck. This multicenter, open-label, single arm study enrolled patients with pathologically confirmed recurrent and/or metastatic ACC of the head and neck for whom at least 1 line of systemic chemotherapy had failed as well as a disease radiographic progression was suggested within three months. The primary endpoint of this study was progression-free survival (PFS). Apatinib was administered as 500 mg daily. Secondary endpoints included best objective response (BOR), disease control rate (DCR), overall survival (OS), and toxicity (Clinical trial information: NCT02775370). Between April 2016 and May 2017, 32 patients were registered and evaluable for efficacy analysis. The median progression-free survival (PFS) of all 32 patients was 4 months (range 1-11 months). Tumor shrinkage was achieved in 24 (75%); 14 (43.8%) had confirmed partial responses (ORR). Seventeen (53.1%) patients had stable disease, 8 of whom had disease stability for > 4 months, DCR was 90.6% (29/32). The recurrent diseases had better response rates than metastatic diseases. Twenty (62.5%) patients experienced dose reduction during treatment. The most common grade 3/4 treatment-related AEs were hypertension (31.3%), hand-foot syndrome (9.4%), proteinuria (12.5%) and fatigue (6.3%). Of three possibly drug-related SAEs recorded in the study, 2 deaths occurred and were both considered to be the result of disease progression. The other one was grade 2 diarrhea needing hospitalization. Apatinib exhibited objective efficacy in R/M ACC patients with manageable toxicity. Further prospective studies that enroll more patients with longer follow-up time are warranted.