The standard treatment for advanced head and neck squamous cell carcinoma (HNSCC) combines radiation therapy with the chemotherapy drug cisplatin. However, about one-third of patients—often older adults or those with underlying health conditions—can’t tolerate its side effects. These patients often face worse outcomes, and until now, there was no clear consensus on the best alternative treatment.
Groundbreaking results from the multicenter HN004 trial, co-developed by MCW Cancer Center researchers, showed that combining cetuximab—a targeted therapy that slows cancer growth—with radiation therapy is a more effective and tolerable option for these vulnerable patients. The findings, recently published in The Lancet Oncology, establish a new standard of care while addressing a critical gap in cancer treatment.
“Cisplatin is a highly effective but toxic drug we’ve relied on for over 50 years. This study demonstrates that radiation with cetuximab is an effective alternative for older and less healthy patients,” said Stuart Wong, MD, Professor of Hematology and Oncology, and Vice Chair of the NRG Oncology Head and Neck Cancer Committee that developed the trial. “Together with my partner and first author of the study, Dr. Loren K. Mell, a radiation oncologist at the University of California in San Diego, we aimed to create a trial that reflects the real-world patients we treat every day, ensuring no one is left behind in our pursuit of better care.”
“Historically, head and neck cancer studies have focused on super healthy patients—often younger and fitter than those we treat in real life. This approach makes sense for testing aggressive treatments and pushing the boundaries of what's possible, but it overlooks a significant patient population: older adults and those with health conditions. HN004 addresses this gap by focusing on vulnerable patients who can’t get the standard treatment,” added Dr. Wong.
The phase 2/3 HN004 trial compared two therapies: cetuximab and durvalumab, an immunotherapy that helps the immune system attack cancer. While durvalumab has shown success in treating metastatic cancers, cetuximab proved more effective for patients, with better progression-free survival (PFS) and fewer side effects. Musaddiq Awan, MD, Associate Professor of Radiation Oncology, and the study’s co-author noted, “The difference in outcomes was so significant that researchers stopped the trial early. Cetuximab, not immunotherapy, remains a standard of care in this setting.”
“Immunotherapy drugs like durvalumab have shown promise in advanced cancers, but this trial clarified that cetuximab is the better choice for patients receiving upfront radiation. These findings will shape national and global treatment guidelines, improving patient care and avoiding unnecessary use of immunotherapy in this setting,” added Dr. Awan.
The MCW Cancer Center was instrumental in the study, contributing to patient enrollment and trial design through its leadership in NRG Oncology, one of five national cancer cooperative groups currently funded by the National Cancer Institute as part of the National Clinical Trials Network. The Center has led other transformative head and neck trials like DEHART, which used advanced radiation technology to adapt treatment in real-time based on tumor response, improving outcomes while minimizing side effects.
“The Center’s leadership in HN004, DEHART, and other cutting-edge studies highlight its dedication to advancing innovative head and neck cancer treatments, and to delivering more personalized care for every patient,” said Dr. Awan.
Read the full study in The Lancet Oncology.