Cetuximab With Radiotherapy Found to Be Inferior to Standard Treatment in HPV-Positive Oropharyngeal Cancer

Key Points

  • The third and final interim analysis, done after a median follow-up of 4.5 years, found that overall survival on the cetuximab arm was significantly inferior to the cisplatin arm.
  • Adverse events of renal toxicity, hearing loss, and bone marrow suppression were more common in patients in the cisplatin arm, whereas body rash was more common in the cetuximab arm.

An interim analysis of data from a randomized clinical trial of patients with human papillomavirus (HPV)-positive oropharyngeal cancer found that treatment with radiation therapy and cetuximab (Erbitux) is associated with worse overall and progression-free survival compared to the current standard treatment with radiation and cisplatin. The trial was designed to see if cetuximab with radiation would be less toxic than cisplatin with radiation without compromising survival for patients with the disease.

Full study details will be presented in the Plenary Session at the American Society for Radiation Oncology (ASTRO) Annual Meeting in San Antonio, Texas. Findings from the trial will later be published in a peer-reviewed journal. 

The phase III trial, which closed enrollment in 2015, was funded by the National Cancer Institute (NCI) and led by NRG Oncology, part of NCI’s National Clinical Trials Network. The data monitoring committee overseeing the trial recommended releasing the data after an interim data analysis showed that cetuximab with radiation was associated with inferior overall and progression-free survival, compared to cisplatin and radiation.

The U.S. Food and Drug Administration had previously approved cetuximab with radiation for patients with head and neck cancer, including oropharyngeal cancer. Cetuximab with radiation is an accepted standard of care, especially for patients who cannot tolerate cisplatin. 

Study Background

“The goal of this trial was to find an alternative to cisplatin that would be as effective at controlling the cancer, but with fewer side effects,” said Andy Trotti, MD, of the Moffitt Cancer Center, a co-lead investigator of the trial. “We were surprised by the loss of tumor control with cetuximab.” 

There has been a lot of recent interest in the cancer clinical research community in evaluating the de-escalation of therapies for cancers that have a good prognosis, such as HPV-positive cancer of the oropharynx. The goal is to improve patients’ quality of life and reduce long-term toxic effects, without compromising treatment efficacy. HPV-positive oropharyngeal cancer is frequently diagnosed in individuals in their 50s and 60s and is associated with high survival rates, providing the incentive for this trial. Moreover, the incidence of this type of cancer has increased rapidly in recent years in the United States. 

This trial’s primary objective was to determine whether the substitution of cetuximab for cisplatin with radiation would result in comparable overall survival, while reducing toxic side effects with improved long-term quality of life. The trial enrolled 849 patients with HPV-positive oropharyngeal cancer who were randomly assigned to receive either cetuximab or cisplatin with radiation therapy. The study had three planned interim analyses. 

Final Interim Analysis Findings

The third and final interim analysis, done after a median follow-up of 4.5 years, found that overall survival on the cetuximab arm was significantly inferior to the cisplatin arm. Overall rates of serious (grade 3–5) adverse events were similar for patients in both groups. However, as the researchers expected, toxic side effects were different, with adverse events of renal toxicity, hearing loss, and bone marrow suppression more common in patients in the cisplatin arm, whereas body rash was more common in the cetuximab arm. All patients in this trial had completed therapy at the time of this analysis.

“This trial is the first randomized clinical trial specifically designed for patients with HPV-positive oropharyngeal cancer, and it establishes cisplatin with radiation as the standard of care,” said Maura Gillison, MD, PhD, of The University of Texas MD Anderson Cancer Center, the other co-lead investigator.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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