Benefit of Cabozantinib in Head and Neck Squamous Cell Carcinoma

Pembrolizumab with cabozantinib exhibit promising Phase II outcomes in patients with recurrent metastatic head and neck squamous cell carcinoma (HNSCC), with an ORR of more than 50%  (Abstract # 6008)

Exelixis’ flagship molecule, cabozantinib, in combination with pembrolizumab, achieved the primary endpoint of ORR in Phase II clinical trial. Pembrolizumab is an immune checkpoint inhibitor approved for treating patients with recurrent/metastatic Head and Neck Squamous Cell Carcinoma (HNSCC). The analysis showed that RECIST 1.1 ORR was 54%, with an overall clinical benefit of 91%. At a median follow-up of 10.6 months, the 1-year progression-free survival rate was 54.0%, and the median progression-free survival was 14.6 months. The 1-year overall survival (OS) was 68.4%.

  • The one-year OS rate for the 17 patients with a PD-L1 combination positive score (CPS) of less than 20 was 54.9%.
  • The one-year OS rate for the 17 patients with a CPS score of 20 or above was 83.6%.

The most common adverse effects were fatigue, diarrhea, hypothyroidism, and others. The most common grade 3/4 treatment-related AEs were aspartate aminotransferase (AST) increase (8.3%) and hyponatremia (8.3%). The drug was also well-tolerated, with an acceptable safety profile.

KOL insights:

“It is necessary to develop more treatment options for patients who have advanced after definitive treatment. These positive results tend to motivate the development of treatments for patients who face unsatisfactory outcomes.”– Expert Opinion


Head and neck squamous cell carcinomas (HNSCC) are the most common head and neck cancer types. Treatment of head and neck cancer is quite challenging. The existing approved medications have limited efficacy. For patients with recurrent and metastatic HNSCC, more treatment alternatives with better response rates and outcomes than existing therapies are required.

Cabozantinib is approved in the United States under the brand name Cabometyx for the treatment of individuals with renal cell carcinoma (RCC), hepatocellular carcinoma (HCC), and differentiated thyroid cancer (DTC). Cabozantinib's promising results have laid the groundwork for additional research into the drug's potential for treating patients with recurrent metastatic HNSCC. It is important to mention that several companies are also attempting to make a name for themselves in HNSCC, either with novel targets or classes (i.e., LAG-3, novel vaccines, and others) or drugs with a convenient route of administration (i.e., intratumoral). The emerging landscape of Head and Neck cancer is highly competitive, and therapies with long-lasting responses and fewer safety concerns will get an advantage. Cabozantinib, if it continues to perform well in future trials, Cabozantinib might emerge as an effective tyrosine kinase inhibitor in the HNSCC treatment space