Abstract 2752: In vivo evaluation of dacomitinib (PF-00299804) in patient-derived salivary gland tumor models: Identification of a potential treatment options for adenoid cystic carcinoma
Authors: Wick Michael J. , Estrada Vanessa E. , Nieves Francis E. , Kelly Scott G. , Tolcher Anthony W. , Patnaik Amita , Kaufman Jeffrey , Lopez-Casas Pedro Pablo , Calvo Emiliano , Hidalgo Manuel , Papadopoulos Kyriakos P. 
Published: August 2012

Adenoid cystic carcinoma (ACC) is an uncommon form of malignant neoplasm that arises within secretory glands including the major and minor salivary glands of the head and neck, trachea, lacrimal gland, breast, skin, and vulva. Standard treatment options for this malignancy include resection and local radiation therapy, although chemotherapy is sometimes used to control metastatic or locally recurrent disease. Patients with ACC may survive for years due to latent tumor growth and lack of lymph node metastasis; however, the high rate of recurrence and metastasis to the lungs lead to a poor prognosis beyond ten years. While specific molecular abnormalities that underlie this disease process are unknown, improved understanding of ACC tumor biology and oncogenesis has provided some molecular targets for its treatment. Recently human epidermal growth factor receptors (HER) family members including EGFR (HER1) and HER2 have been found overexpressed in salivary gland carcinomas and HER2 has also a role in this type of cancer as in many cancer types. Dacomitinib is an orally available, highly selective irreversible small molecule inhibitor of the HER family of tyrosine kinases. Figitumumab is a fully human monoclonal antibody targeting the insulin-like growth factor 1 receptor (IGF-1R). In a recent phase I trial, combination of these two agents resulted in partial tumor responses in two ACC patients as well as minor responses in other indications. To further examine the potential benefit of these agents in ACC, we evaluated single agent and combination activity of dacomitinib and figitumumab in five patient-derived preclinical ACC tumor models including ACCx5M1, ACCx6, ACCx9, ACCx14 and ACCx16. Endpoints for each study were a mean control tumor volume of approximately 1 cm3 or sixty-days following treatment initiation. In these studies dacomitinib and figitumumab were well tolerated at the evaluated treatment regimens. Modest activity was reported with dacomitinib alone which did not reach statistical significance. However, single agent figitumumab demonstrated statistically significant (p&lt;0.05) tumor growth inhibition in two of five models and combination of dacomitinib and figitumumab was found active in three of five models. Partial tumor responses were reported in ACCx6 and ACCx14 studies with figitumumab and combination treatment, respectively and minor tumor regressions noted with combination treatment in ACCx5M1. Results from these studies suggest a role for the IGF-1 pathway in ACC and further demonstrate the utility of patient-derived models for translational studies.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2752. doi:1538-7445.AM2012-2752