The investigational drug alpelisib (previously known as BYL719) was able to overcome head and neck cancer (HNC) resistance to the antiepidermal growth factor receptor (EGFR) treatment cetuximab, and combining alpelisib with cetuximab was found to be beneficial, according to a study presented at the recent American Association for Cancer Research meeting in San Diego.
In the phase Ib clinical trial, about 25% of the patients with recurrent and metastatic head and neck cancer who were treated with a combination of cetuximab and alpelisib benefited from the therapy.
"Most head and neck cancers are driven by activation of the EGFR pathway. Cetuximab is a drug that targets EGFR and is effective in this setting, but cancers often become resistant to this therapy," stated Pamela Munster, MD, a professor of medicine and the director of the Early Phase Clinical Trials Unit at the University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, in a press release. "Treatment resistance is often conveyed through activation of the PI3K/AKT/mTOR pathway, and alpelisib is an inhibitor of this pathway."
The study included 37 patients with recurrent/metastatic squamous cell carcinoma of the head and neck resistant to platinum-based chemotherapy. Of these patients, 32 received 300 mg of alpelisib once daily and the other five received 400 mg of alpelisib once daily plus cetuximab.
The overall response rate was 11% and the disease control rate was 54% among the 37 patients in the study. Of the seven patients who had relapsed on prior cetuximab therapy, treatment with alpelisib resulted in one partial response and disease control in five, with a disease control rate of 71%.
In the group of 32 patients who received alpelisib alone, four had a confirmed partial response and 16 had stable disease, five of whom had unconfirmed partial responses.
The researchers had previously conducted preclinical studies using mice bearing cetuximab-sensitive and cetuximab-resistant esophageal cancer cells to study the effect of a combination of alpelisib and cetuximab. They found that a combination of alpelisib and cetuximab had an additive effect in mice with cetuximab-sensitive cancer cells leading to tumor regression. This combination restored sensitivity to cetuximab in mice with cetuximab-resistant cancer cells.
Based on the data from preclinical studies and phase Ib results testing the combination, the team is currently conducting the phase II part of the trial to test a combination of cetuximab and 300 mg of alpelisib once daily in patients who have squamous cell carcinoma of the head and neck.
The study was funded by Novartis Pharmaceuticals.
