Evolving Role of Immunotherapy in Head and Neck Cancer

Drugs that block cancer's deceptive ways

Immune Cells Attacking Cancer Cells
Immune cells attacking cancer cells. Tim Vernon/Science Photo Library/Getty Images

Squamous cell cancer of the head and neck is the sixth most common cancer in the world and accounts for approximately one to two percent of all cancer deaths. One major problem lies in the treatment of people with metastatic or recurrent head and neck cancer, as the chance of survival is generally poor.

The good news is that research is progressing, and doctors are beginning to use immunotherapies in this population of patients.

Immunotherapy is a novel treatment that appears safe and improves symptoms and even survival time for some people, based on early scientific studies.

Understanding the Basics of Head and Neck Cancer

Before you can grasp how these immunotherapies work, it's good to get a handle on what certain "head and neck" terms mean.

What Is Squamous Cell?

Squamous cells are skinny, flat cells that line the surface of the skin, the digestive and respiratory tracts, and certain organs in the body.

Examples of areas where squamous cell carcinoma (cancer) can develop include these sites:

  • Head and neck
  • Skin
  • Cervix
  • Vagina
  • Lung
  • Anus

What Does Malignant Mean?

A malignant tumor (as opposed to a benign tumor, which is non-cancerous) in the head and neck region refers to a collection of cancer cells that are growing uncontrollably and may or may not yet have invaded normal healthy tissue.

Immunotherapy and other therapies like chemotherapy are used to treat malignant tumors, as these are harmful and potentially fatal.

Where Is Head and Neck Cancer Located?

The term 'head and neck" can be perplexing, as it covers a large surface area. In other words, you may wonder what it means exactly when someone is diagnosed with this type of cancer.

Head and neck cancer refers to tumors that develop in one of these many areas:

  • Lip/mouth
  • Back of the mouth or throat (called the oropharynx)
  • Lower part of the throat that is behind and next to the voice box (called the hypopharynx)
  • Upper part of the throat behind the nose (called the nasopharynx)
  • Voice box (called the larynx)

What Causes Head and Neck Cancer?

In the past, the development of head and neck cancer was linked to tobacco and alcohol use. But in the last ten years or so, the development of some head and neck cancers has been linked to infection with certain types of human papillomaviruses (HPV). For instance, scientific data has shown that a type of HPV called HPV-16, which causes cervical cancer and anal cancer in men and women, is associated with cancer of the oropharynx.

Infection with HPV is extremely common, yet only a small percentage of people develop cancer from it. This is because most people's immune systems clear the infection.

Even more interesting than discovering the link between HPV and head and neck cancer, is the finding that the incidence of head and neck cancers attributed to HPV has increased. On the other hand, the incidence of head and neck cancers attributed to tobacco and alcohol use has decreased. Why this change? Experts suspect that it could be due to a societal change in sexual activities—specifically, that oral sex has become more common.

Right now, there is particular interest in how to best treat HPV-positive head and neck cancers, as their biology is different from HPV-negative tumors. With that, experts are taking a closer look at various immunotherapy strategies to treat HPV-associated cancers.

What Are Immune System Checkpoints?

Immune system checkpoints are proteins normally located on a person's immune system cells (called T cells). T cells are like policeman seeking out trouble (cancer or infection) within the body. When the T cell encounters another cell, it evaluates the cells using proteins located on its surface to determine if the cell is "normal" or "abnormal." If abnormal, the T cell will initiate an attack against the cell.

But during this attack, how are normal, healthy cells protected? This is where checkpoint proteins come into play. Checkpoint proteins lay on the surface of T cells and ensure that healthy cells are left alone.

Cancer is devious in that it actually makes these checkpoint proteins (a true copycat) to avoid an attack from a person's immune system. One checkpoint protein expressed on the surface of cancer cells to sneak by the immune system is PD-1.

But now scientists have discovered that they can block PD-1 on cancer cells, so that cancer is indeed detected by a person's immune system. This is where immunotherapy comes into play, and these PD-1 blocking drugs are called immune system checkpoint inhibitors.

Immunotherapy to Treat Head and Neck Cancer

There are two immune system checkpoint inhibitors that were FDA approved in 2016 for treating people with metastatic and/or recurrent head and neck squamous cell carcinoma.

Metastatic cancer refers to head and neck cancer that has spread to other areas of the body, while recurrent head and neck cancer refers to cancer that has progressed despite treatment with a platinum-based chemotherapy regimen (for example, cisplatin).

These two immunotherapies are called Keytruda (pembrolizumab) and Opdivo (nivolumab).

Pembrolizumab

Early studies show pembrolizumab has a good safety profile and can be effective in shrinking some people's cancer.

In one phase II study, 171 people with head and neck cancer that progressed despite being previously treated with chemotherapy and cetuximab (a monoclonal antibody therapy) received an infusion of pembrolizumab every three weeks.

Overall response rate was 16 percent, and the median duration of response was 8 months. Response rate refers to the percentage of participants whose cancer shrinks or disappears in response to the treatment.

In terms of safety, 64 percent of the participants experienced a treatment-related adverse effect, but only 15 percent experienced a grade three or four adverse event (severe or life threatening).

The most common adverse effects were:

  • Fatigue
  • Hypothyroidism (an underactive thyroid gland)
  • Nausea
  • Elevation of a liver enzyme
  • Diarrhea

Overall, the only immune system-related adverse effects were hypothyroidism, hyperthyroidism, and pneumonitis.

On a side note, immune system adverse effects are a big concern with immunotherapies, as there is concern that a person's immune system will attack not only cancer cells but healthy tissue too. In the case of pneumonitis, a person's lungs are targeted, which can make breathing difficult.

The big picture is that receiving an immunotherapy is a delicate process, as the body and the medication work together to determine what is bad (cancerous) and what is normal and healthy.

Phase III studies of pembrolizumab are ongoing. A phase III study means that pembrolizumab will be compared against the standard of care medication to see how it fares, like whether or not it's more effective.

Nivolumab

In a phase III study, over 350 people with recurrent/metastatic squamous cell carcinoma of the head and neck, whose disease had progressed within six months of receiving platinum-based chemotherapy, were randomized to receive either nivolumab every two weeks (given as an infusion through the vein) or a standard therapy (methotrexate, docetaxel, or cetuximab).

Results revealed a significantly longer overall survival in the people who received nivolumab versus those who received the standard therapy (median survival of 7.5 versus 5.1 months, respectively).

In addition, the one-year survival rate was 36 percent in the nivolumab group versus 16.6 percent in the standard therapy group. In other words, the one-year survival rate more than doubled.

In terms of safety, grade 3 or 4 adverse effects occurred in 13 percent of the nivolumab group versus 35 percent of the standard therapy group. In the nivolumab group the most common adverse effects were:

  • Fatigue
  • Nausea
  • Rash
  • Decreased appetite
  • Itching

In general, adverse effects related to the thyroid were more common in the nivolumab group (7.6 percent developed hypothyroidism versus 0.9 percent in the standard therapy group).

Pneumonitis occurred in 2.1 percent of the people treated with nivolumab, and two people died (one from pneumonitis and one from elevated calcium levels in the blood). One person in the standard-therapy group died from a lung infection related to the treatment given.

Interestingly, a questionnaire that assessed the quality of life at the end of the study, found no significant decline in quality of life after treatment with nivolumab. On the other hand, there was a significant decline in quality of life in several areas (for example, pain, physical and social functioning, sensory problems) after treatment with chemotherapy.

A Word From Verywell

Immunotherapy is already changing the face of cancer treatment. It's legitimate, it "makes sense," and is promising.

Remember though, treating head and neck cancer is a complex process. There are many factors that go into deciding exactly how your doctor wants to treat your particular tumor, like your history of prior therapies, whether you have other medical problems, and the toxicities linked to a certain drug.

Remain an advocate for your own cancer health by gaining knowledge. The journey is long and arduous, but try to seek out comforts and joys along the way too.

Sources:

Bauml J et al. Pembrolizumab for platinum- and cetuximab-refractory head and neck cancer: Results from a single-arm, phase II study. J Clin Oncol. 2017 May 10;35(14):1542-49.

Brockstein BE, Vokes E. Treatment of metastatic and recurrent head and neck cancer. In:UpToDate, Posner MR (Ed), UpToDate, Waltham, MA.

Economopoulou P, Perisanidis C, Giotakis EI, Psyrri A. The emerging role of immunotherapy in head and neck squamous cell carcinoma (HNSCC): anti-tumor immunity and clinical applications. Ann Transl Med. 2016 May;4(9):173.

Ferris RL et al. Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med. 2016 Nov 10;375(19):1856-67.

National Cancer Institute. (2017). Head and Neck Cancer. Health Professional Version: Research. 

Continue Reading