Merkel cell carcinoma (MCC) is a rare and especially dangerous form of skin cancer, which makes treating it especially challenging. At all stages of MCC, physicians usually remove the primary tumor through excisional surgery. This is rarely the only treatment required, however. MCC has a high risk of recurrence, or spreading, to the local lymph nodes, so doctors usually recommend additional therapies to prevent this. In cases where the cancer has metastasized to distant sites beyond the lymph nodes, including organs (stage IV), chemotherapy was the frontline treatment — until recently.
In March 2017, the FDA approved the checkpoint blockade therapy drug avelumab (brand name Bavencio) for the treatment of patients with stage IV MCC. In December 2018, the FDA approved a second therapy of this type, pembrolizumab (Keytruda), for patients with recurrent locally advanced or metastatic MCC. There has been tremendous excitement about these groundbreaking therapies among physicians who treat MCC, and for good reason. But those less familiar with MCC and immunotherapy in general may not understand what all the fuss is about. What is this new treatment, and why is it such a big step forward?
Arming the Immune System
Immunotherapy, unlike traditional cancer treatments like chemotherapy, does not kill cancer cells with an outside drug. The therapy is designed to inspire the body’s own defenses to take out cancer —something it has trouble doing on its own.
“A healthy immune system is very good at seeing and destroying a large variety of viruses and bacteria,” says Kelly Paulson, MD, a senior hematology/oncology fellow in Fred Hutchinson Cancer Research Center’s Clinical Research Division. “Normally when a precancer develops, the immune system recognizes and eliminates it using a special type of cell called a killer T cell.”
The body has checks on this system, however, to make sure the immune system does not attack and kill normal parts of the body (which is what happens when a person has an autoimmune disease, like lupus). Cancer is a clever disease and has learned about the immune system’s checks and balances. It has consequently evolved to dodge our body’s alert system and is able to invade and multiply without triggering T cells. “MCC basically tricks the body,” Dr. Paulson says. “It tells the immune system, ‘Calm down; don’t worry about me!’”
That’s where immunotherapy comes in, she says. The treatments are meant to retrain a patient’s body to do what it should be doing naturally. Immunotherapy strengthens the immune system so it can once again see, recognize and hopefully kill the foreign invader that is Merkel cell carcinoma.
Immunotherapy is not just another option for treating late stage MCC, Dr. Paulson stresses. For many patients, it’s a vastly superior one. One of the advantages immunotherapy has over chemotherapy is the body’s long memory. “You can get vaccinated against some diseases when you’re a child and still be protected 40, 50, 60 years later,” she says. “Since what we’re doing with this therapy is augmenting your body’s natural way of fighting cancer, those immune cells stay with you even after you finish treatment. We’re learning that responses to immunotherapy can last for months and even, in many cases, years.”
A cancer treatment that not only makes cancer go away but stay away is invaluable to patients. Chemotherapy wasn’t cutting it for many of them. Dr. Paulson says that while about two-thirds of MCC patients who receive chemotherapy see their tumors shrink, after about three months almost everyone’s cancer started to grow back.
“When we look at immunotherapy, at three years after treatment not even half of the patients’ cancer had grown back if they experienced that initial shrinkage,” Dr. Paulson says. “There’s a remarkable difference in how long the effects of the treatment can last, and that’s why everyone’s really excited about immunotherapy.”
In addition, immunotherapy is often less time consuming and less likely to cause serious side effects than chemotherapy treatment. Side effects can range from fatigue and flu-like symptoms to colitis and inflammation of the lungs, called pneumonitis. Most patients do not suffer from very serious side effects, but doctors monitor closely for them.
After seeing the success of immunotherapy in stage IV MCC patients, researchers are exploring if the therapy could benefit other MCC patients. “Surgery and radiation are important for early stage Merkel, to help keep the cancer away after it’s been cut out,” Dr. Paulson explains. “We’re wondering now, since immunotherapy works so well in the metastatic setting, if could it be useful for helping to prevent recurrence in patients whose MCC has not yet spread to distant sites? Researchers are currently testing this application of immunotherapy, called adjuvant therapy, in clinical trials.
Though immunotherapy is clearly a promising new option for MCC patients, there are still plenty of questions about the treatment that need answering. There is no way to tell who might respond to treatment, so what may inspire a useful response in the immune system of one patient may have no effect on another’s. At this point, between one-half and two-thirds of patients who undergo treatment will benefit. “When you walk in the door, there’s no way for us to tell if you’re in the group of patients that is going to get a really remarkable, wonderful response and years of prolonged life from the treatment or not,” Dr. Paulson says.
The same goes for side effects. Although they’re typically less intense than the side effects seen with chemotherapy, between one in three and one in five patients will suffer from a serious side effect during treatment.
Immunotherapy researchers are still hard at work learning how to maximize the benefits and minimize the costs, but Dr. Paulson says the treatment is still unequivocally the best choice for the majority of stage IV MCC patients. “If someone tells you to do chemotherapy before immunotherapy, seek a second opinion before starting treatment,” she says. “The number one thing I want to get across is that if you have metastatic MCC, you are way more likely to be alive in three years if you get immunotherapy rather than chemotherapy.”
This post is part of a patient education series made possible through a grant from EMD Serono and Pfizer. Learn more at EMDSerono.com.