Cabozantinib Plus Atezolizumab Warrants Further Study in Treatment of Advanced Head and Neck Cancer

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A challenging patient population with advanced head and neck cancer may have a new treatment option, according to data presented during the 2022 Society for Immunotherapy of Cancer (SITC) Annual Meeting.1

Results from Cohort 17 of the COSMIC-021 study showed that the combination of the kinase inhibitor cabozantinib and the PD-L1 inhibitor atezolizumab demonstrated clinical activity in patients who had previously received platinum-containing chemotherapy and some immune checkpoint inhibitor therapy. The safety profile was also comparable to previous trials that have reported cabozantinib with immune checkpoint inhibitors, the study authors reported.

“For oncologists working with head neck cancer, the treatment of patients who have experienced disease progression and have recurrent or metastatic disease remains extremely challenging despite the advances seen in the immunotherapy era,” said lead study author Saad A. Kahn, MD, Assistant Professor of Oncology at Stanford Cancer Institute and Stanford University. “These results, in addition to those from the phase II study of cabozantinib plus pembrolizumab in immune checkpoint inhibitor–naive patients, warrant further evaluation of the combination of cabozantinib with an immune checkpoint inhibitor.”

Saad A. Kahn, MD

Saad A. Kahn, MD

As Dr. Kahn explained, patients with recurrent or metastatic squamous cell carcinoma of the head and neck after chemotherapy have a poor prognosis and limited therapeutic options. Immune checkpoint inhibitors alone or in combination with chemotherapy have been shown to increase overall survival. Recent data, however, also suggested the combination of multiple kinase inhibitors such as cabozantinib with immune checkpoint inhibitors may be effective in this patient population.2

Study Methods

Cohort 17 of the COSMIC-021 study evaluated cabozantinib plus atezolizumab in patients with recurrent squamous cell carcinoma of the head and neck. Patients enrolled on the study had experienced disease progression during or after prior platinum-containing chemotherapy and had received at least two prior lines of systemic anticancer therapy. Of note, prior treatment with an immune checkpoint inhibitor, EGFR-targeted therapy, and radiotherapy were allowed for patients on study. Primary tumors in the oropharynx, oral cavity, hypopharynx, or larynx were allowed, but patients with tumors in the nasopharynx were excluded.

The dose of cabozantinib adopted for this study was 40 mg orally daily combined with atezolizumab at the standard dosing delivered intravenously every 3 weeks. Tumor assessments were every 6 weeks for the first year followed by every 12 weeks subsequently. The primary endpoint of this study was to determine the overall response rate by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, as assessed by the individual investigators.

Disease Control, but No Complete Responses

As Dr. Kahn reported, a total of 30 patients with head and neck cancer were enrolled in the study, most of whom had received multiple prior lines of therapy. The median number of prior systemic anticancer therapy agents was 2.5, and 30% of patients had received a prior immune checkpoint inhibitor.

The overall response rate as assessed by the investigator was 17%. Although there were no confirmed complete responses, there were five partial responses. Five patients were not evaluable, said Dr. Kahn, and the remainder had progressive disease. The overall combined disease control rate was 60%, as assessed by investigators using RECIST version 1.1 criteria, and the median duration of response was 9.7 months. “Even patients who had prior exposure to immune checkpoint inhibitors still had the ability to demonstrate a partial response when they were treated with cabozantinib and atezolizumab,” said Dr. Kahn. “Patients with no demonstrated PD-L1 positivity also had a response rate greater than 30%.”

For patients with no previous exposure to immune checkpoint inhibitor therapy, median progression-free survival was 2.9 months, and overall survival was 9.2 months in this population. Dr. Khan also noted that cabozantinib plus atezolizumab was well tolerated, with no unexpected side effects observed. 

“The toxicity of the combination regimen was similar to other trials that have combined pembrolizumab with an anti–PD-1 therapy,” Dr. Khan concluded. 

DISCLOSURE: Dr. Kahn has served as an advisor or consultant to Eisai, EMD Serono, and Foundation Medicine and has received honoraria for lectures from Roche Pakistan.


1. Rottey S, Santoro A, Arnold S, et al: Cabozantinib plus atezolizumab in advanced head and neck cancer previously treated with platinum-containing chemotherapy. 2022 SITC Annual Meeting. Abstract 570. Presented November 10, 2022.

2. Burtness B, Harrington KJ, Greil R, et al: Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048). Lancet 394:1915-1928, 2019.

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