The investigator-sponsored study was led by principal investigator Nabil F. Saba, MD.
Ninety-one percent of the participants with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC)—who typically have few treatment options available after existing therapies —experienced clinical benefit in a phase 2 trial testing a combination of the tyrosine kinase inhibitor cabozantinib, with the immune check point inhibitor in pembrolizumab. At a median follow-up of 10.6 months, the one-year progression-free survival rate was 54%, meaning that in 54% of patients’ the cancer did not worsen in one year of beginning trial treatment, and median progression-free survival was 14.6 months.
The study's findings will be presented at the 2022 American Society of Clinical Oncology (ASCO) annual meeting during Oral Abstract Session: Head and Neck Cancer on Friday, June 3, beginning at 2:45 CT.
The investigator-sponsored study was led by principal investigator Nabil F. Saba, MD, professor and vice chair in hematology and medical oncology, co-director of the Head and Neck Cancers Multi-Disciplinary Program and the inaugural Lynne and Howard Halpern Chair in Head and Neck Cancer Research at Winship Cancer Institute of Emory University.
Treatment options are rare for HNSCC
"Metastatic head and neck cancer is a challenging disease to treat," says Saba, "particularly after disease progression on prior therapy, which usually includes radiation and chemotherapy."
HNSCC comprises head and neck cancers that begin in the squamous cells that line the mucosal surfaces of the head and neck and account for about 90% of all head and neck cancers. HNSCC is classified by its location, and can occur in the oral cavity, oropharynx, nasal cavity and paranasal sinuses, nasopharynx, larynx or hypopharynx.
"Treatment options for patients with metastatic head and neck squamous cell carcinoma are limited, leaving a critical unmet need for this community," says Vicki L. Goodman, MD, executive vice president of product development and medical affairs and chief medical officer for Exelixis, the Almeda, California-based pharmaceutical company supporting the study. "Through our research, including our investigator-sponsored trials program, we continue to advance toward our goal of bringing new treatment options to people with difficult-to-treat cancers."
The study
In this phase 2 trial, eligible patients had recurrent and metastatic HNSCC that was deemed inoperable, a life expectancy of at least three months, and an Eastern Cooperative Group (ECOG) Performance Status of 0 or 1. The ECOG scale describes a patient's level of functioning in terms of their ability to care for themselves, daily activity and physical ability (walking, working, etc.). The scale is one way to define the population of patients to study in a trial and guides physicians who enroll patients into those studies.
Of the 36 patients who could be evaluated, 61% had cancer in the oropharynx, 16% in the nasopharynx, 11% in the larynx, 6% in the hypopharynx and 6% in the oral cavity. Eighty-nine percent of the patients had received prior radiation therapy and all had received prior chemotherapy.
On the study’s treatment regimen, patients received pembrolizumab intravenously over 30 minutes on day 1 and cabozantinib orally once daily on days 1-21. Cycles were repeated every 3 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients were followed up to 2 years.
Cabozantinib is a targeted therapy that works by interfering with the ability of cancer cells to grow and spread and is approved for the treatment of patients with advanced renal cell carcinoma (RCC); for the treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib; for patients with advanced RCC as a first-line treatment in combination with nivolumab; and for adult and pediatric patients 12 years of age and older with locally advanced or metastatic differentiated thyroid cancer (DTC) that has progressed following prior vascular endothelial growth factor receptor (VEGFR)-targeted therapy and who are radioactive iodine-refractory or ineligible.
Pembrolizumab is an immune checkpoint inhibitor – a type of immunotherapy that blocks checkpoint proteins that stop the immune system from attacking the cancer cells – and is approved as a first line HNSCC patients with positive PD-L1, as well as second-line treatment for HNSCC, after platinum-based chemotherapy, to treat inoperable or metastatic melanoma, metastatic non-small cell lung cancer in first-line treatment for metastatic bladder cancer if patients cannot receive cisplatin-based chemotherapy and have high levels of PD-L1, for the treatment of adult and pediatric patients with refractory classic Hodgkin's lymphoma (cHL), and recurrent locally advanced or metastatic esophageal squamous cell carcinoma.
Offering hope for patients running low on it
It's easy for people with rare cancers like HNSCC who have exhausted their available treatment options to lose hope. But studies like this one edge the field, and patients' prospects, forward a step at a time.
As both a clinician and the study’s principal investigator, Saba says, "These results showing promising clinical activity of cabozantinib in combination with pembrolizumab are encouraging for these patients who face poor outcomes with existing therapies."
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