Adding an extra immunotherapy drug to single-drug treatment for head and neck cancer could shrink tumor size further and improve survival, trial findings suggest, as well as offer biological markers for how to best personalize treatment.
The Phase II study showed that two different combinations of immunotherapy drugs doubled or tripled the response rate of patients with head and neck squamous cell carcinomas (HNSCCs) compared with monotherapy treatment.
Up to a third of the patients receiving multiple drugs saw more than half their tumor disappear after just a month of treatment, according to the study published in Cancer Cell.
The findings could lead to the next generation of patient-tailored, neoadjuvant immune checkpoint inhibitor (ICI) regimens, using targetable biomarkers.
“In this trial, we were able to specifically identify biological signatures that helped us decide which immunotherapy combination was best to use,” explained researcher and UNC Lineberger Comprehensive Cancer Center executive director Robert Ferris, PhD.
“The Lymphocyte Activation Gene-3, or LAG-3, protein was a good marker for some people while the CTLA-4 protein was a good marker for others. 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.”
HNSCC makes up the seventh most common cancer worldwide, with approximately 890,000 new HNSCC cases and 450,000 deaths each year. It accounts for around 4.5% of cancer diagnoses and deaths worldwide, but overall survival for locally advanced disease could be improved, particularly for HPV- cancer.
Ferris and co-workers aimed to enhance the anti-tumor activity of an anti-PD1 antibody by the addition of an anti-CTLA4 antibody or anti-LAG3 antibody among previously untreated patients with locally advanced HPV+ and HPV- HNSCC who were candidates for surgical resection.
Those with a history of autoimmune disease or with current or previous histories of immune-modulating agents were excluded from participation.
A total of 42 participants were assigned to one of three immunotherapy treatment arms: nivolumab alone, nivolumab plus ipilimumab, and nivolumab plus relatlimab. One patient later withdrew their consent to participate.
Both immunotherapy combinations appeared to perform equally well, which was attributed to their ability to activate tumor-specific T lymphocytes, an immune T cell that targets cancer cells.
To address whether successful ICI regimens acted through similar or distinct pathways, the researchers additionally characterized transcriptional and proteomic dynamics of CD8+ tumor-infiltrating lymphocytes.
The team found distinct CD8+ T cell dynamics associated with response to different neoadjuvant cancer immunotherapies. Different ICI combinations targeted specific CD8+ tumor-infiltrating lymphocyte activation states and drove their differentiation toward a common CD8+ effector or tissue-resident memory T cell population in major responders.
“Defining the CD8+ T cell states at baseline associated with ICI response may provide potential biomarkers that could play a crucial role in tailoring ICI therapies to specific patient profiles,” the researchers concluded.
