Multitargeted Tyrosine Kinase Inhibitors in Head and Neck Cancer
Posted: Thursday, April 4, 2019
The most promising clinical results of multitargeted tyrosine kinase inhibitors (TKIs) for patients with head and neck squamous cell carcinoma have occurred when multitargeted TKIs are tested in combination with other therapies, according to a review of novel targeted treatments presented in Expert Opinion on Investigational Drugs. The successful of use of such multitargeted TKIs may ultimately depend on enhancing our understanding of which patients are most likely to benefit from such treatment based on tumor characterization.
“The future success of multitargeted TKIs will rely on identification, in preclinical models and clinical trials, of predictive biomarkers of response and mechanisms of innate and acquired resistance,” concluded Jennifer R. Grandis, MD, the Robert K. Werbe Distinguished Professor in Head and Neck Cancer, Otolaryngology, University of California, San Francisco, and colleagues.
The study authors focused on early-stage investigations of multitargeted TKIs for patients with head and neck squamous cell carcinoma. They found that the most informative clinical trials incorporated tumor profiling such as next-generation sequencing so the biology of the patient’s tumor could be assessed in the context of treatment responses. Additionally, the authors suggested, the most successful use of multitargeted TKIs are likely to be based on strong evidence of antitumor activity in the relevant preclinical models, including well-characterized head and neck squamous cell carcinoma cell lines, patient-derived xenografts, and immunocompetent head and neck squamous cell carcinoma models.
For instance, the use of the antiangiogenic TKI nintedanib as well as other targeted inhibitors such as the PI3K inhibitor BYL719, the EGFR/HER2 inhibitor poziotinib, and the CDK4/6 inhibitor abemaciclib (ClinicalTrials.gov identifier NCT03292250) is under investigation. Dr. Grandis and colleagues explored in detail the potential role of these and other multitargeted TKIs in the treatment of patients with head and neck squamous cell carcinoma.
Disclosure: The study authors’ disclosure information may be found at tandfonline.com.