Head, Neck Cancer Cancer Drug May Overcome Cetuximab Resistance
(HealthDay News) — The investigational drug alpelisib (previously known as BYL719) appears to inhibit activation of the pathway that leads to resistance to cetuximab, an anti-epidermal growth factor receptor agent used in the treatment of head and neck cancer. These findings were presented at the American Association for Cancer Research's special conference "Targeting the PI3K-mTOR Network in Cancer," held from September 14–17 in Philadelphia.
Pamela Munster, MD, of the University of California in San Francisco, and colleagues tested the combination of BYL719 and cetuximab in vivo in a cetuximab-sensitive and a cetuximab-resistant xenograft model of esophageal squamous cell carcinoma. In a phase Ib study, BYL719 was administered in combination with cetuximab in adults with recurrent or metastatic squamous cell carcinoma of the head and neck that was resistant or intolerant to platinum-based chemotherapy; prior cetuximab therapy was allowed.
The researchers found that the addition of BYL719 to cetuximab showed an additive effect in the cetuximab-sensitive model. BYL719 restored sensitivity to cetuximab in the cetuximab-resistant model. In the phase Ib study, as of March 10, 2014, 37 patients have received BYL719 and cetuximab, and the overall response rate is 11%. Based on the data from preclinical studies and the phase Ib study, the combination of alpelisib and cetuximab for squamous cell carcinoma of the head and neck is being explored in a phase II study.
"Treatment resistance is often conveyed through activation of the PI3K/AKT/mTOR pathway, and alpelisib is an inhibitor of this pathway," Munster said in a statement.
The study was funded by Novartis, the developer of alpelisib (BYL719).