An experimental targeted drug could provide a fresh chance for people with recurring head and neck cancer that has grown resistant to other treatments, a new clinical trial says.
Ficlatuzumab used in combination with the already approved targeted drug cetuximab (Erbitux) significantly improved progression-free survival in relapsed head and neck cancer patients, according to results from a phase II trial.
The results are particularly encouraging because the ficlatuzumab/cetuximab combo only worked in patients whose cancers aren’t driven by human papillomavirus (HPV) infection, said lead researcher Dr. Julie Bauman, director of the GW Cancer Center at George Washington University in Washington, D.C.
“People with HPV-positive virally driven cancer have a better prognosis. They usually respond better to just about any therapy that’s put in front of them,” Bauman said.
Patients with “the worst of the worst prognosis, with HPV-negative disease, was the group that appeared to disproportionately benefit, which was unexpected and quite gratifying,” Bauman said. HPV-negative head and neck cancers are typically driven by alcohol or tobacco use or exposure to occupational pollutants.
The combo therapy had a 38% response rate in HPV-negative head and neck cancer patients. In those patients, tumors shrank by at least 30%.
“This was a very sick patient population, because these were patients who had had their cancer come back after initial treatment, and they were all resistant to chemotherapy, targeted therapy and immunotherapy,” Bauman said. “These patients truly had no standard options left.”
Head and neck cancers recur in about half of patients with HPV-negative cancers, Bauman said.
Patients with recurring head and neck cancers have a life expectancy of two years, and those whose cancer has grown resistant to other therapies have less than six months, Bauman said.
Both cetuximab and ficlatuzumab are targeted therapies, or drugs that work by interrupting specific ways in which cancer cells grow and spread.
Cetuximab works by blocking epidermal growth factor (EGF), a protein that promotes growth in normal cells and can spur the spread of cancer.
But head and neck cancers in some patients eventually find a way around cetuximab, by latching onto other growth factors and hormones in the human body, Bauman said.
Ficlatuzumab cuts off one of those “escape mechanisms” for head and neck cancer, hepatocyte growth factor (HGF).
“This is a drug that’s an antibody that blocks a growth factor produced by the cells surrounding the tumor,” said Dr. Marshall Posner, head of the head and neck oncology program at Mount Sinai Medical Center in New York City. “That growth factor binds to an enzymatic target on the cancer cells, and by binding to it, it turns that enzymatic target on and helps the cancer cells grow.”
Specifically, the drug blocks the HGF from triggering a pro-growth enzyme called cMet, Bauman said.
“Ficlatuzumab mops up the HGF,” Bauman said. “It serves as a sponge. The antibody attaches to the HGF and prevents it from triggering cMet.”
For this clinical trial, researchers randomly treated 58 patients with either ficlatuzumab alone or ficlatuzumab and cetuximab.
The patients who got the combo therapy had an average progression-free survival of 3.7 months, the results showed.
Progression-free survival was 4.1 months in HPV-negative patients versus 2.3 months in HPV-positive patients.
“It turned out that blocking both pathways was where we saw the signal, was where we saw a doubling of progression-free survival as well as a response rate in the total study population of 19%, which in a refractory population is still clinically meaningful, especially when two of those six responses were complete without any additional evidence of cancer,” Bauman said.
Only HPV-negative cancers responded to the combo treatment, possibly because only those head and neck cancers are spurred on by the cMet enzyme, Posner said.
“This is an area where we don’t have good treatment,” Posner noted. “They’ve discovered something for these very hard to treat cancers in a situation where there’s a great deal of resistance, and they’ve identified what we call biomarkers that tell us which patients to treat.”
The combination therapy “really entirely blocked a large pathway of growth for the cancer cells, so the cancer cells really took a step back,” Posner said. “And they did it in a population of patients who were resistant to chemotherapy, resistant to immunotherapy.”
Posner added that side effects were generally mild, and typically what one would see with cetuximab treatment.
Based on these results, Bauman and her colleagues are crafting a phase III clinical trial that will put the ficlatuzumab/cetuximab combo’s effectiveness to the test in patients with HPV-negative head and neck cancer.
The phase III trial is expected to kick off by early 2024 at the latest, Bauman said, and will take about three years to complete.
Outside of the immunotherapy drugs pembrolizumab and nivolumab, which were approved by the U.S. Food and Drug Administration for head and neck cancer in 2016, there haven’t been many advances in this field of cancer research, Bauman said.
The phase III trial will show whether the combo worked, or whether there’s something else going on in these patients that allowed them to live longer with head and neck cancer, Posner said.
The new trial results were published online March 28 in the Journal of Clinical Oncology.
The American Cancer Society has more about head and neck cancers.
SOURCES: Julie Bauman, MD, MPH, director, GW Cancer Center, George Washington University, Washington, D.C.; Marshall Posner, MD, head, head and neck oncology program, Mount Sinai Medical Center, New York City; Journal of Clinical Oncology, March 28, 2023, online
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