Burtness Discusses Next Steps With Immunotherapy in Head and Neck Cancer

Barbara Burtness, MD

Immunotherapy continues to advance the care of patients with head and neck cancer, with researchers now exploring combining these therapies together, as well as adding immunotherapy to standard approaches, explains Barbara A. Burtness, MD.

For example, the ongoing phase III CheckMate-651 trial is investigating the combination of nivolumab (Opdivo) plus ipilimumab (Yervoy) versus standard of care as a first-line treatment for an estimated 490 patients with recurrent or metastatic squamous cell carcinoma of the head and neck (NCT02741570). The primary endpoints of the study are overall survival and progression-free survival.

OncLive: What is the current role of immunotherapy in head and neck cancer?

In an interview with OncLive, Burtness, a professor of medicine at Yale Cancer Center, discussed the current role of immunotherapy in head and neck cancer and potential combination regimens on the horizon.Burtness: Immunotherapy has made a change in the management of patients with metastatic and recurrent head and neck cancer. For patients who have been previously exposed to platinum therapy, either nivolumab or pembrolizumab (Keytruda) has been shown to be an appropriate drug that leads to responses—some of which are durable responses.

What promising combinations are currently being investigated that include immunotherapy?

Our main question is, “How do we best select patients who can use these agents even earlier during their treatment?”There are a couple of different approaches to combination therapy. One is to try to integrate immunotherapy with standard treatment approaches. In head and neck cancer, chemoradiation or chemotherapy and cetuximab (Erbitux) for metastatic recurrent disease do have an impact; they lead to responses and they improve survival. One strategy is to attempt to build on the anticancer effectiveness of existing therapies by adding immunotherapy.

The other strategy is to prime the immune system better. We are seeing combinations of PD-1 or PD-L1 inhibitors together with CTLA-4 inhibitors in large phase III trials that have been conducted to look at those questions. We don’t have the answers to those yet.

What research are you currently working on?

The last thing that researchers are doing is looking at novel immunotherapies in combination with PD-1 inhibitors. In head and neck cancer, one that we are quite interested in now is epacadostat. We are very interested in the role of immunotherapy in patients with radioresistance. When you take a patient with locally advanced disease, whether they have HPV-negative or HPV-positive disease, you can generally expect a complete response following the conclusion of chemoradiation. If a patient has persistent disease, the accepted approach has been to take that patient to a salvage operation, with the recognition that this patient has a very high risk for recurrence.

What are the biggest challenges still facing the treatment landscape of head and neck cancer?

On an investigator-initiated trial that we have ongoing at Yale Cancer Center, Dr Zain A Husain is the principal investigator. We are taking patients who have persistent disease after radiation that is proven by biopsy; rather than taking them straight to surgery, we are exposing them to pembrolizumab (Keytruda) with the hope that we can initiate an immune response against the cancer prior to taking them to salvage therapy. The fact is that although immunotherapy can lead to responses that are extremely durable, there are many patients who do not respond to immunotherapy. The question will be, “Are there ways that we can understand the causes of resistance and exploit them so we can lead to more DNA damage and augment inflammation, or can we do something else that will make the patients more responsive to immunotherapy?”

Conversely, have we turned our back on targeted therapy that is not directed against the immune system? The experience with the NCI-MATCH trial and other approaches to targeting drivers in head and neck cancer has been disappointing because so many of these patients have mutations of tumor suppressor genes.

Is there a place for CAR T-cell therapy in head and neck cancer?

In that context, people are starting to get interested in exploring synthetically full approaches with targeted therapy to methodically active kinases that are downstream from p53. We have seen some data with WEE1 inhibitors that I am also particularly interested in looking at. That is going to be a strategy that will continue to be pursued in the immunotherapy-resistant patients. Not at the moment. The work is just beginning with that approach. A question that we have will be, “What is it that CAR T-cell therapy is achieving that we previously couldn’t?” With the pharmacologic approaches to immunotherapy, we may develop a better understanding of patient subsets and the manipulation of the immune system.