Soon, a global, stage III randomized clinical trial could result in a paradigm shift in how certain head and neck cancers are treated.
The clinical trial, called KEYNOTE-689 and overseen by the Merck pharmaceutical company, is the result of specific research initiated by head and neck cancer specialists at Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine in St. Louis.
“Preliminary reports in 2013 and 2014 showed that immunotherapy could be an effective treatment for recurrent cancers,” said Douglas Adkins, MD, a Washington University medical oncologist who co-leads the Head & Neck Tumor Center at Siteman.
“My colleague Dr. Ravi Uppaluri and I wanted to know if administering immunotherapy before surgery would improve the cure rates of patients with locally advanced head and neck cancer. We were the first group to explore this treatment strategy specifically with head and neck cancer and among the first to explore this strategy in patients with any cancer type,” Adkins said.
More than 800,000 new cases of head and neck cancer are diagnosed each year. Most are linked to tobacco use and are usually treated with surgery followed by radiation therapy. Half of these patients, however, develop a recurrence of their cancer.
Drs. Adkins and Uppaluri wanted to find ways to lower the rate of recurrence and subsequent death from head and neck cancer. In 2014, they opened an investigator-initiated trial that evaluated the effectiveness of a specific immunotherapy drug, pembrolizumab, in two groups — one receiving pembro before surgery; the other group receiving it before surgery and again after radiation therapy. Not only did the clinical trial find the drug safe for patients, it also resulted in a major breakthrough.
“One dose of pembrolizumab given before surgery killed tumor cells in about half of the 66 patients enrolled in the study,” Dr. Adkins said. “When we doubled it to two doses, it intensified the degree of tumor kill.”
Other clinical trials found that a greater tumor kill after immunotherapy correlated with a lower risk of relapse. Merck, which helped fund the investigator-initiated trial first at WashU, took notice of the continued promising results. In 2017, Merck sponsored the KEYNOTE-689 global trial, which involved 704 patients with locally advanced head and neck cancer. Patient enrollment was finished in September 2023, and Dr. Adkins and his colleagues are eagerly waiting for the results to be published.
“I am excited about what I’ve seen because we have been involved in this latest trial, too,” Dr. Adkins said. “We are hopeful that the results of the KEYNOTE-689 trial will transform the current standard of care for patients specifically diagnosed with locally advanced head and neck cancer.”
Within the past year, neoadjuvant immunotherapy has been studied in several key clinical trials for patients with non-small cell lung cancer, triple-negative breast cancer and melanoma. All have found that immunotherapy coupled with surgery led to lower rates of recurrent cancer when compared to surgery alone.
“The best outcomes were observed when immunotherapy was administered before versus after surgery,” Dr. Adkins said.
He has been involved in more than 100 clinical trials while at Siteman Cancer Center and Washington University, and he says the academic environment enables patients not only to receive the best in standard-of-care therapies but also to access a wide range of clinical trials when appropriate. That track record also means pharmaceutical companies look to WashU as a leader in transforming ideas into novel therapies.
“Positive results in other cancer types validate that the novel treatment strategy we conceived of in 2014 was promising and warranted further investigation,” Dr. Adkins said. “What we are doing here is altering how we think about treating not only head and neck cancer, but other cancers too.”
To view the list of active clinical trials at Siteman, go to siteman.wustl.edu/clinical-trials.