Many cases of head and neck squamous cell carcinoma (HNSCC) are caused by human papillomavirus (HPV); however, HNSCCs can be caused by a variety of factors, including p16INK4A inactivation (an inhibitor of cyclin-dependent kinase 4A) and overexpression of the oncogene cyclin D1. This results in the stimulation of cyclin-dependent kinase 4 and 6 (CDK4/6). Overexpression of cyclin D1 can also cause resistance to epidermal growth factor receptor (EGFR) inhibitors. To overcome this resistance, researchers conducted a study to determine if patients with recurrent or metastatic HNSCC could achieve an objective response to the CDK4/6 inhibitor and EGFR inhibitor combination of palbociclib and cetuximab.
For this study (NCT02101034), published in The Lancet Oncology, 62 patients were enrolled. The patients were split into two groups: 30 patients in group 1 who had platinum-resistant HNSCC, and 32 patients in group 2 who had cetuximab-resistant, HPV-unrelated HNSCC. To be eligible, patients had to have measurable disease according to Response Evaluation Criteria in Solid Tumors, version 1.1, and an Eastern Cooperative Oncology Group performance status of 0 to 2. In addition, participants had to be 18 years old or older, and have experienced disease progression on platinum but be cetuximab-naive (group 1) or have experienced disease progression on cetuximab (group 2).
All of the patients were administered 125 mg per day of oral palbociclib on days 1 through 21 and 400 mg/m2 intravenous cetuximab on cycle one, day one, then progressed to 250 mg/m2 once per week. Medication cycles lasted 28 days.
The results revealed that 39% of patients in group 1 achieved an objective response. In group 2, 19% of patients achieved an objective response. Grade 3/4 neutropenia was the most common treatment-related adverse event associated with taking palbociclib.
The study authors conclude, "In patients with platinum-resistant or cetuximab-resistant HPV-unrelated HNSCC, palbociclib and cetuximab results in promising activity outcomes. Further studies of CDK4/6 inhibitors are warranted in HPV-unrelated HNSCC."
For More Information
Adkins D, Ley J, Neupane P, et al (2019). Palbociclib and cetuximab in platinum-resistant and in cetuximab-resistant human papillomavirus-unrelated head and neck cancer: a multicenter, multigroup, phase 2 trial. Lancet Oncol. [Epub ahead of print] DOI:10.1016/S1470-2045(19)30405-X
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