Cetuximab in Advanced HPV-Positive HNC

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Human Papillomavirus (HPV)-positive patients with head and neck cancer HNC tend to be younger, healthier, and likely to live with their disease for many years, making it important to identify low-risk patients where treatment de-escalation is an option. For these individuals, treatment toxicities can be limited by adopting a surgical approach, such as transoral robotic surgery (TORS). TORS initially gained interest in earlier stage disease, but emergent data reveal there may be a set of patients with advanced disease in whom TORS is also an option.

Barbara Murphy, MD, explains that some oncologists consider radiation without chemotherapy in patients with earlier stage HPV. It is preferable to minimize toxicity associated with radiation in low-risk patients with locally advanced disease, which Murphy says can be accomplished by using targeted therapy, such as cetuximab, the only approved epidermal growth factor receptor inhibitor in squamous cell carcinoma of the head and neck.

A phase III trial (Radiation Therapy Oncology Group 1016) evaluating cisplatin versus cetuximab in low-risk patients with HPV-positive tumors demonstrated that the addition of cetuximab to radiation therapy resulted in improved local regional control and overall survival compared with radiation therapy alone. Individuals receiving cetuximab combined with radiation yielded a 10% absolute improvement in overall survival at 3 years and 5 years, which Ezra Cohen, MD, notes is now used as level-one evidence for the use of cetuximab with radiation in locally advanced HNC. Cohen adds cetuximab was shown to be effective regardless of whether patients had HPV-positive or HPV-negative disease; both populations appeared to benefit to the same degree.

Murphy refers to another treatment approach currently under investigation that involves decreasing the amount of radiation delivered to patients. In this approach, HNC patients initially receive induction chemotherapy. Patients with good response receive shorter courses of radiation therapy with either platinum-based or cetuximab-based therapy. Patients without a good response return to the standard course of treatment, radiation combined with chemotherapy.

Murphy comments new approaches currently under investigation in the HPV-positive population involve individuals that are either early stage or low-risk. The concern for high-risk patients is cure, rendering de-escalation of therapy in this group inappropriate, and Murphy predicts these patients will likely need a novel therapeutic approach.

Cohen elaborates on the EXTREME clinical trial, which was studied in a population of recurrent and metastatic disease in which cure was no longer an option. The clinical trial evaluated patients who had never been treated for their disease and randomized them to receive either a doublet (cisplatin or carboplatin with 5-flurouracil) or cetuximab added to doublet therapy. Results of EXTREME were the first show a difference in recurrent metastatic disease, where cetuximab improved response rate from 20% to 35%, progression-free survival from 3 months to over 5 months, and overall survival from 7 months to 10 months. Based on these data, cetuximab was approved for the treatment of recurrent metastatic first-line patients in combination with chemotherapy.