Study Provides Roadmap to More Personalized Treatment in Head and Neck Cancer

Researchers have found that people with advanced head and neck squamous cell carcinoma, coupled with the KRAS-variant inherited genetic mutation, have significantly improved survival when given a short course of the drug cetuximab in combination with standard chemotherapy and radiation. The study was led by UCLA Jonsson Comprehensive Cancer Center member Joanne Weidhaas (photo), M.D., Ph.D., in collaboration with colleagues at the NRG Oncology Radiation Therapy Oncology Group (RTOG). The scientists discovered that people with both head and neck squamous cell carcinoma and the KRAS-variant who were treated with standard treatment, but not with cetuximab, had a higher risk of failing treatment and developing metastatic disease. In 2006, researchers discovered the KRAS-variant, an inherited genetic mutation found in up to 25 percent of people with cancer. The KRAS-variant is a biomarker that disrupts a class of important regulators, called microRNAs, which were discovered in 2000. The mutation has been shown to predict response to cancer therapy for many cancers, including head and neck cancer. It was not previously understood exactly how this biomarker worked. The current standard of care for advanced head and neck squamous cell carcinoma involves chemotherapy and radiation. However, this approach typically results in a 50-percent treatment failure. Cetuximab is a monoclonal antibody that was previously shown to be beneficial for these patients when combined with radiation and chemotherapy; yet a randomized phase 3 trial was unable to identify those who benefited from cetuximab. Dr. Weidhaas’ team analyzed available samples from the NRG Oncology RTOG 0522 randomized phase 3 clinical trial of cetuximab in combination with chemotherapy and radiation therapy.
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