Author: Brooke McCormick

Jennifer Choe, MD, PhD, shared her thoughts on why head and neck cancer patients relapse after radiation therapy, new head and neck cancer treatment trials, and promising responses from these trials. Choe is a head and neck oncologist at Vanderbilt University Medical Center and was a presenter at The American Journal of Managed Care®’s Institute for Value-Based Medicine® held in Nashville, Tennessee on August 17, 2023.


Can you explain some of the thought behind why there is disease relapse in head and neck cancers after radiation treatment?

There’s a lot of theoretical basis as to why we think this is the case. A lot is driven by just aggressive biology; it’s really not known. Head and neck cancers are considered immune responsive, technically speaking, but the response rates still are pretty low, in general, and whether or not the immune system and head and neck cancer patients are depressed compared to other cancers. I, in theory, think that a part of it is actually the radiation creating an environment where there could be a reduction in the body’s ability to regulate the immune system.

There’s an immune suppressed state for these patients that could be due to radiation of the lymph nodes that’s decreasing the ability for the immune system to respond, but also the local radiation induced immune suppression effects that may be producing a more conducive environment for the cancer to return.

What are some of the trials evaluating new treatment regimens for patients with head and neck cancers?

The 2 big trials that actually did not meet their primary endpoints were 2 chemoradiation trials in the phase 3 stage. They’re combining chemoradiation with immune checkpoint inhibitors concurrently given. We think that this likely could be due to a sequencing issue where they’re actually creating an environment where they’ve ablated the immune prime cells with the chemoradiation given at the same time as the immune checkpoint inhibitor.

Currently, there is actually an ongoing clinical trial with Invoke, which is basically looking at chemoradiation sequentially giving the immunotherapy after chemoradiation as opposed to combined with it. There are other combination therapies of looking at various components where they’re looking at whether or not they can make the radiation more effective, such as XIP [xylanase inhibitor protein] inhibitors to treat in combination with chemoradiation.

There are a number of other clinical trials but they’re more in the recurrent metastatic site, looking at some promising molecules. There are a few eGFR [epidermal growth factor receptor]-based antibodies that have come out, kind of leveraging what we already know about eGFR antibodies cetuximab and panitumumab but trying to actually improve upon that with these novel eGFR antibodies.

What are some promising responses that you’ve seen so far?

Where we’ve seen actually the most promise is actually these eGFR bispecific antibodies. Particularly, BCA-101 is one that has actually really created a lot of buzz at ASCO this year. Mainly in HPV [human papillomavirus] negative cancers, this is in the recurrent metastatic state, but there’s actually been a few eGFR-based therapies that have come through, which has had very promising results. Ficlatuzumab has had some encouraging data, as well, which basically works based off of the eGFR resistance mechanism to try to induce response.

We’re seeing some evidence of some promising agents that are coming through using targeting of what we already knew, which is eGFR overexpression in head and neck cancers, in trying to improve upon what we already have is kind of our traditional cetuximab-based regimens. Hopefully, we can actually make some headway with those in promising clinical trials, not just in a recurrent metastatic setting but possibly pushing it up into the locally advanced setting.