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Downloaded from http://journals.lww.com/co-oncology by BhDMf5ePHKbH4TTImqenVA5KvPVPZ0P5BEgU+IUTEfzO/GUWifn2IfwcEVVH9SSn on 06/05/2020 REVIEW URRENT Potential role of cyclin-dependent kinase 4/6 PINION inhibitors in the treatment of squamous cell carcinoma of the head and neck a a,b Gabrielle van Caloen and Jean-Pascal Machiels Purpose of review Human papillomavirus (HPV)-negative squamous cell carcinoma of the head and neck (SCCHN) is mainly driven by genetic aberrations involved in the cell cycle pathway resulting in cyclin-dependent kinase (CDK) 4 and 6 activation. This supports the investigation of the activity of CDK4/6 inhibitors in this disease. We review the therapeutic potential of CDK4/6 inhibitors in SCCHN. Recent findings CDK4/6 inhibitors in monotherapy have demonstrated cytostatic activity in HPV-negative SCCHN. Combination with epidermal growth factor inhibitors, with phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin pathways inhibitors or with immunotherapy, have shown promising preclinical efficacy. No strong predictive biomarkers of response or resistance have been firmly identified. Phase I clinical trials have demonstrated that palbociclib or ribociclib in combination with cetuximab is well tolerated. A phase II single-arm trial combining palbociclib/cetuximab has shown promising results. Summary Inhibition of CDK4/6 represents a new potential treatment for HPV-negative SCCHN patients. Randomized clinical trials that investigate these compounds in an unbiased manner are needed to
Current Opinion in Oncology – Wolters Kluwer Health
Published: May 1, 2019
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