A phase 2 clinical trial led by Winship Cancer Institute of Emory University shows a combination of two drugs was well tolerated and benefitted 91% of participating patients with recurrent/metastatic head and neck squamous cell carcinoma.
The study, newly reported in Nature Medicine, was led by principal investigator Nabil F. Saba, MD, FACP, the Lynne and Howard Halpern Chair in Head and Neck Cancer Research, co-director of the Head and Neck Cancers Multi-Disciplinary Program at Winship Cancer Institute of Emory University and professor and vice chair of the Department of Hematology and Medical Oncology at Emory University School of Medicine.
The two drugs used in the study were pembrolizumab (brand name Keytruda), an immunotherapy drug that works with the immune system to help fight cancer, and cabozantinib (brand names Cabometyx and Cometriq), a drug known as a multi-tyrosine kinase inhibitor. Cabozantinib targets specific tyrosine kinase receptors important to cell functions that, when blocked, may slow tumor growth. Preclinical and clinical observations suggest cabozantinib also promotes an immune-permissive environment, possibly impacting the immune system’s capacity to fight cancer.
The research builds on earlier evidence that these two types of drugs were potentially good partners to combine—and that combination therapy could work better than therapy using only one drug.
Among the study’s 36 participants 33 were evaluated for response; 17 (52%) had a partial response and 13 (39%) had stable disease, resulting in a clinical benefit of 91%.
“The combination of cabozantinib and pembrolizumab showed a very promising response exceeding 50%, and benefitted 91% of patients with advanced head and neck squamous cell carcinoma,” says Saba.
Importantly, the progression-free survival and overall survival appear to be superior to outcomes observed using the current standard of care in recurrent/metastatic head and neck squamous cell carcinoma, which includes therapy of single anticancer drugs that block the activity of PD-1 and PDL1 immune proteins present on the surface of cells.
The side effects from treatment were similar to those seen in previous studies using combinations of immunotherapy agents and kinase inhibitors.
Saba says the trial “clearly shows” that combining pembrolizumab and cabozantinib is a promising strategy “and ought to encourage the investigation of similar combinations in recurrent metastatic head and neck squamous cell cancers.” Not only that, but he adds, “these findings could have significant implications on the future management of squamous cell carcinomas of different organ sites.”
Saba is considering further evaluation of similar combinations in a larger, more definitive trial that could lead to altering the standard of care for treating metastatic head and neck squamous cell carcinomas.
The study enrolled participants at Emory University in Atlanta (the leading site), and the Moffitt Cancer Center in Tampa, Florida, with multiple investigators participating from both sites. At Moffitt, the study was led by Christine Chung, MD, chair of the Department of Head and Neck-Endocrine Oncology. Emory collaborators included Yong Teng, PhD, a member of Winship’s Cell and Molecular Biology Research Program and associate professor in the Department of Hematology and Medical Oncology at Emory University School of Medicine; and Winship Discovery and Developmental Therapeutics Research Program members Conor Steuer, MD, associate professor of hematology and medical oncology, and Dong M. Shin, MD, professor of hematology and medical oncology.