Head and neck cancers are the seventh most common type of cancer worldwide, according to the 2020 World Cancer Report . Smokers and drinkers, as well as those with HPV infections, are disproportionately affected. The chemotherapy drug cisplatin, when administered alongside radiation therapy, is the gold standard for treating these malignancies. However, more than 30% of patients, including some older adults and those with pre-existing kidney disease or hearing loss, cannot take cisplatin due to severe side effects.
The monoclonal antibody cetuximab, while not as effective as cisplatin, is often used as an alternative in these patients. However, there is currently no consensus on the standard of care for this population. Durvalumab, an immune checkpoint inhibitor, has shown promise for treating a wide range of cancers, and has been proposed as a potentially safer and more effective option than cetuximab, according to Loren Mell, MD, professor and vice chair of clinical and translational research at University of California San Diego School of Medicine Department of Radiation Medicine and Applied Sciences, and co-leader of the UC San Diego Moores Cancer Center Head/Neck Disease Team.
In a clinical trial, Mell and cancer researchers from two dozen other institutions compared the effectiveness of durvalumab and cetuximab — in combination with radiation therapy — in 186 patients with advanced squamous cell carcinoma of the head or neck who were ineligible for cisplatin. They report in The Lancet Oncology that contrary to expectations, cetuximab performed better than durvalumab, with a similar rate of adverse events. As a result, the researchers discontinued the study early. The results were published on November 14, 2024.
"We found that the probability of being alive and free of disease at two years was approximately 64% for cetuximab versus 51% for durvalumab, indicating no evidence of a benefit of durvalumab over cetuximab," said Mell. "We had a lot of reasons to be optimistic about durvalumab, but it turned out to be potentially worse than the standard."
Monoclonal antibodies like cetuximab bind to proteins on the surface of cancer cells, halting their growth and proliferation. In contrast, durvalumab, an immune checkpoint inhibitor, blocks a protein on cancer cells called PDL1, which allows tumors to thrive, allowing the immune system's T cells to attack cancer cells directly. Mell says there is some evidence that durvalumab could still have a place in treating a very specific subset of patients with highly immunoreactive tumors, but more research is needed.
The results have significant implications for the treatment of head and neck cancers. The study — the first of its kind conducted in North America — demonstrated a higher success rate than any previous study of cetuximab in this patient population, and Mell said the drug is likely to become the new standard of care for these patients. The study also revealed that cetuximab showed similar efficacy whether or not a patient's cancer was associated with HPV.
"Our study helps reinforce that radiation with cetuximab is a very good alternative for patients who cannot get standard cisplatin," said Mell. "Historically, this has been an underserved group, so our trial sought to establish an evidence base for this rather unique population that skews very much towards older individuals and those with competing health problems that have in many cases been expressly excluded from clinical trials based on those comorbidities."
Mell says research is in progress to compare cetuximab against competing standard alternatives, such as carboplatin and paclitaxel combination therapy, with new trials under development. In addition, ongoing trials continue to test novel therapeutic agents in conjunction with radiotherapy as an alternative to radiation with cetuximab.
Additional co-authors on the study include: Assuntina G Sacco, UC San Diego, Pedro A. Torres-Saavedra, National Cancer Institute, Stuart J. Wong and Musaddiq J. Awan, Medical College of Wisconsin, Julie A. Kish, Moffitt Cancer Center, Steven S. Chang, Henry Ford Health System, Richard C. Jordan and Sue S. Yom, University of California San Francisco, Tian Liu, Emory University, Minh Tam Truong, Boston Medical Center, Eric W. Winquist, London Regional Cancer Program, Vinita Takiar and Trisha Wise-Draper, University of Cincinnati, Jared R. Robbins, University of Arizona College of Medicine, Cristina P. Rodriguez, University of Washington, Beth M Beadle and Quynh-Thu Le, Stanford University School of Medicine, Christina Henson, University of Oklahoma, Samir Narayan, Trinity Health Ann Arbor, Sharon A. Spencer, University of Alabama Birmingham, Steven Powell, Sanford USD Medical Center, Neal Dunlap, University of Louisville, Kenneth Shung Hu, New York University Langone Medical Center, Henry S. Park, Yale University School of Medicine, Julie E. Bauman, George Washington University and George Washington Cancer Center, and Jonathan Harris, American College of Radiology.
The study was funded, in part, by the National Cancer Institute (grants UG1CA189867, U10CA180868, U10CA180822, U24CA196067, and U24CA180803).
