Ezra Cohen, MD
The future of immunotherapy in head and neck squamous cell carcinoma (HNSCC) lies in combinations involving anti PD-1/PD-L1 agents, says Ezra Cohen, MD, adding that chimeric antigen receptor (CAR) T-cell therapy may have a role, as well.
In an interview with OncLive
, Cohen, professor of medicine, division of Hematology/Oncology, University of California, San Diego, associate director for Translational Science, Moores Cancer Center, discussed anti–PD-1/PD-L1 combination regimens in HNSCC, the potential for CAR T-cell therapy, and remaining challenges with immunotherapy in the field.
OncLive: What is the current role of immunotherapy in head and neck cancer?
When we talk about immunotherapy in head and neck cancer, we are really talking about squamous cell carcinoma where the exploration of anti–PD-1 and anti–PD-L1 has focused. Right now, we have 2 approved agents in patients with recurrent or metastatic disease—the first is pembrolizumab (Keytruda) and the second is nivolumab (Opdivo), in the order of their FDA approvals.
For now, we are using immunotherapy as standard-of-care in patients who have either recurred after curative intent therapy within 6 months of completing that therapy, or in patients who have had first-line platinum-containing therapy and have progressed. So, it’s really focused now on patients with recurrent or metastatic disease.
What combinations are being investigated?
For the future of immunotherapy in HNSCC, we are really thinking about combinatorial therapy. And what I mean by that, is now trying to integrate the agents we know have efficacy as single agents, so be it pembrolizumab, nivolumab, or even durvalumab (Imfinzi) and avelumab, (Bavencio).
Now, we are beginning to think—how will they fit with either immunotherapies and/or standard of care? First of all, there is a lot of excitement around combination immunotherapy, we are beginning to see data about doublets and the potential to really double response rates or even more for agents that are combined with anti–PD-1. We saw a very nice example at ASCO in June of 2017, where pembrolizumab and nivolumab were combined with IDO inhibitors, specially epacadostat. And what we saw was an almost 40% response rate in patients who were let’s say, relatively not heavily pretreated. That is an amazing response rate for a doublet immunotherapy.
Moreover, we are beginning to explore these agents in combination with standard chemotherapy, mostly platinum-containing regimens. And now, finally, in the locally advanced setting—in combination with radiation or with chemotherapy/radiation. Of course, those data sets will take some time to mature, we won’t get those data for another few years, but the tremendous promise has now led to extending these agents into earlier phases of disease.
Is there a place for CAR T-cell therapy in head and neck cancer?
When we think about other types of immunotherapy that we could apply to head and neck cancer, we naturally have to think about adoptive cell therapy—and mostly we are thinking about T cells. We have to just step back for a second and realize that when we talk about adoptive cell transfer or adoptive cell therapy, it comes in many forms. It can come into the form of simple tumor-infiltrating lymphocytes (TILs), that is, taking TILs out of a person’s tumor, expanding them ex vivo, and then putting them back in. Or it can be much more sophisticated in the form of CAR T-cell therapy.
Now, the question of whether CARs can actually be applied to head and neck cancer is a good one, and one that is being intensively investigated. The real problem in head and neck cancer—as it is with many solid tumors—is finding the right target. What we’ve learned from other experience with CAR therapy is if you have the right target, you can see tremendous responses, acute lymphoblastic leukemia (ALL) is one such example with CD19. But, if you have the wrong target, patients can get into trouble—and there have even been fatalities, and unfortunately, there have been some notorious studies with that.
And so, the first challenge is finding the right target—and there are some, primarily stem cell antigens that are expressed exclusively or almost exclusively on cancer cells. ROR1 is one such target, and people are beginning to look at that in head and neck cancer. There may be some others that are a little bit earlier in development.