A combination of two immunotherapies may improve treatment response among patients with head and neck squamous cell carcinomas compared with just one immunotherapy drug, according to a recent study published by Li et al in Cancer Cell.
Background
Head and neck squamous cell carcinomas occur in the oral cavity, pharynx, hypopharynx, larynx, nasal cavity, and salivary glands—representing the seventh most common cancer diagnosis across the world. With an estimated 890,000 new cases and 450,000 deaths per year, head and neck squamous cell carcinomas account for about 4.5% of cancer diagnoses and deaths globally.
Current head and neck squamous cell carcinoma treatments can be disfiguring and negatively impact a patient’s quality of life. Therefore, shrinking a tumor prior to surgery can increase the likelihood that a surgeon can preserve a patient’s tongue and voice box.
“[Our] group has conducted preoperative trials in head and neck cancers for over 15 years, and the ability to shrink tumors with existing drugs prior to surgery has been relatively disappointing. While a recent trial has shown that single-drug immunotherapy provides a benefit, it only worked in a small number of patients,” stressed senior study author Robert L. Ferris, MD, PhD, Executive Director of the University of North Carolina at Chapel Hill Lineberger Comprehensive Cancer Center.
Study Methods and Results
In this study, researchers randomly assigned 42 patients—1 of whom later withdrew consent—to receive one of three immunotherapy regimens: nivolumab plus ipilimumab, nivolumab plus relatlimab, or nivolumab alone.
The researchers discovered that both immunotherapy combinations appeared to perform equally well. They then analyzed the immune cells in each patient’s tumor following 1 month of immunotherapy to determine which types of immune cells were activated to fight the cancer cells. The researchers attributed the drugs’ performance to their activation of tumor-specific T lymphocytes that specifically recognize and attack cancer cells.
“In our clinical trial, we compared two different combinations of immunotherapy drugs to using a single immunotherapy drug,” detailed Dr. Ferris. “[We] found that either combination regimen doubled or tripled the response rate vs the single immunotherapy and led to a survival benefit. Up to [one]-third of patients who received two drugs saw over 50% of their tumor disappear after only 1 month of treatment,” he added.
Following surgical removal of a tumor that shrunk with treatment, the T lymphocytes remained alive and were circulating in the patients’ bodies, providing surveillance that can increase long-term survival benefit.
Conclusions
The researchers indicated that some of the cells and targets they identified could help individualize treatment benefit in this patient population.
“In this trial, we were able to specifically identify biological signatures that helped us decide which immunotherapy combination was best to use. The LAG-3 protein was a good marker for some [patients] while the CTLA-4 protein was a good marker for others,” Dr. Ferris detailed. “The immune status or markers a patient might have at diagnosis can help dictate which regimen is best to select for their treatment, and because of this marker’s promise, we have filed a patent for our diagnostic paradigm,” he continued.
As a result of their findings, the researchers have extended their trial to include another 40 patients. They plan to use a higher dose of relatlimab and hope to observe greater responses and longer survival in the expanded trial, which is ongoing.
Disclosure: For full disclosures of the study authors, visit cell.com.
