Expert Discusses Evolving Treatment Options in Head and Neck Cancer

Jared Weiss, MD

The development of new agents for patients with head and neck cancer continues to evolve, particularly for immunotherapy regimens, according to Jared Weiss, MD.

“There are multiple clinical trials that are near reporting looking at the role of single- or double-agent immunotherapy for the first treatment for recurrent or metastatic head and neck cancer,” says Weiss.

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

In an interview with OncLive, Weiss, assistant professor, UNC Lineberger Comprehensive Cancer center, discussed the evolving role of immunotherapy and other promising developments in head and neck cancer.At the current time, the role of immunotherapy in head and neck cancer is restricted to recurrent metastatic head and neck cancer. We’re mostly talking about patients who have been treated for cure—sometimes with multiple attempts at cure—who are no longer curable. This is either as a consequence of metastatic disease, meaning a cancer that spread outside of the local regional area, or cancer that has recurred enough times that the patient is out of surgical and radiation options.

We're talking about patients who have been previously treated or are typically platinum refractory. That’s where nivolumab (Opdivo) and pembrolizumab (Keytruda) have their FDA approval and where their standard use is found.

However, we’re actively investigating these agents as well as others in other contexts. There are multiple clinical trials that are near reporting looking at the role of single or double agent immunotherapy for the first treatment for recurrent or metastatic head and neck cancer. There are multiple clinical trials integrating these agents into a cure.

These fall into 2 or 3 basic areas. They’re being studied as induction chemotherapy so either immunotherapy alone or immunotherapy given with chemotherapy before an attempt at cure, such as surgery, radiation, or chemoradiotherapy. Second, they’re being evaluated together, concurrent with radiation and then there is at least one study looking at them in the adjuvant context.

What combinations are being investigated in immunotherapy?

These studies are very important because the average patient with head and neck cancer is not incurable in contrast to many other cancers. The average head and neck cancer is local or locoregionally advanced and being treated for cure, so there is real hope that these agents can improve the cure rates in those contexts. Multiple combinations are being [explored] for immunotherapy in head and neck cancer. We know that we have approval of PD-1 agents and we will soon have PD-L1 agents in the recurrent metastatic setting. We are going to have data within months for the combinations with CTLA-4, such as ipilimumab (Yervoy) and nivolumab or durvalumab (Imfinzi) and tremelimumab.

The other combination that shows early promise is the combination of PD-1 and IDO. IDO is a catalytic enzyme involved in tryptophan metabolism and can influence the immunosuppressive tumor microenvironment. We saw some early data at ASCO that perhaps showed early promise for that combination.

What role do CDK4/6 inhibitors have in the head and neck and cancer space?

Is there anything that you are currently working on that you would like to discuss?

There are many combination studies beyond that going on. Once you get past the PD-1/CTLA-4 combination and the PD-1/IDO combination, you get into the realm of deep speculation and opinion for what is going to hold promise, but one has high hopes that with so many things being studied, more than 1 will hit. At the current time, there is no standard FDA approved role for CDK4/6 inhibitors. However, there are multiple clinical trials looking at them in combination with other agents, either to improve efficacy of therapy, to decrease neutropenia, or both. We all tend to favor our own work. I have multiple clinical trials that I am privileged to be a part of that try to incorporate immunotherapy agents into a cure.

I have a clinical trial of pembrolizumab together with radiation, which is a collaboration between my institution, UNC, Fox Chase Cancer Center, Johns Hopkins Medicine, and The University of Chicago Medicine, looking to ultimately replace cisplatin with a higher cure rate and less of the dramatic toxicity.

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

I am also very excited about a study that combines durvalumab with carboplatin and nab-paclitaxel as induction chemotherapy prior to surgery for hard to cure patients.There are 2 major categories of challenges that I would say are facing us in head and neck cancer and they are perhaps what every cancer faces. The first being that our treatments—the surgeries, chemotherapy, and radiation—are still brutal. Radiation can influence a lot of speech, swallowing, and other functional deficits. Our chemotherapy can induce permanent toxicities.

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

Is there anything else you would like to discuss?

The second problem is that we’re not curing everyone. We have very high rates of non-cure, particularly with HPV-negative cancer, that remains a massive unmet need. I believe that there is a place for CAR T-cell therapy in head and neck cancer. In particular, HPV-positive cancers have the E6 and E7 antigens that are promising for CAR-T therapy. I would also highlight that not all cellular therapy is CAR-T therapy. I have the privilege of being involved in a study of an autologous modified T-cell product that looks to treat metastatic recurrent HPV-positive head and neck cancer. We've had a lot of great conversations about how to better cure patients, how to decrease the morbidity of treatments, and how to increase the cure rates of patients, but there is nothing better than prevention. One of the most important abstracts at ASCO that is perhaps one of the least spoken about in head and neck cancer was an abstract investigating a population level HPV vaccination. The first author was Maura L. Gillison, MD, PhD, and what she showed was that the HPV vaccine appears to be extremely effective in preventing oropharyngeal infection.

She also showed high rates of non-vaccination amongst both boys and girls. HPV vaccines not only prevent cervical cancer, but there is also a strong reason to believe that it can also prevent oropharynx cancer.