This page was reviewed under our medical and editorial policy by
Herbert L. Duvivier, MD, JD, Hematologist and Medical Oncologist
This page was updated on February 24, 2023.
The skin cancer melanoma can be aggressive and, if not caught early, difficult to treat. Doctors have had some success with different chemotherapies, but they don’t always work.
Immunotherapy is one of the newest treatments for advanced melanoma that shows promise. Immunotherapy uses medicines to stimulate the immune system so that it finds and attacks cancer cells.
The immune system is a strong force, and it requires a delicate balance to stop it from harming cells it shouldn't. Immune “checkpoints” are supposed to prevent this from happening. T-cells—proteins on the surface of immune cells—serve as these checkpoints, or brakes, and when they work properly, they help prevent diseases such as cancer. The checkpoints turn the immune response on or off as needed.
Sometimes, T-cells bind with partner proteins. When this happens, it prevents the immune system from turning on and destroying cancer cells, instead allowing them to grow. Normally, T-cells are meant to kill cancer cells.
Some immune checkpoint inhibitors known as PD-1 (programmed cell death protein 1) inhibitors have been developed to intercept this process and are used to treat advanced melanoma.
The U.S. Food and Drug Administration has approved two PD-1 inhibitors for melanoma. Keytruda® (pembrolizumab) and Opdivo® (nivolumab) turn on T-cells that boost the body’s immune response to melanoma. They’ve been shown to shrink tumors that can’t be surgically removed or have spread elsewhere in the body.
These PD-1 inhibitors may also be used to treat advanced melanoma when lymph nodes are involved and after surgery. They’re used to lower the risk of recurrence.
Tecentriq® (atezolizumab) targets PD-L1, a protein found on some normal cells as well as in high amounts on some cancer cells. The drug is designed to block this protein so that the body’s immune system kicks into gear and fights melanoma.
This PD-L1 inhibitor may be used with other drugs if melanoma can’t be surgically removed or if it has spread to other parts of the body. Other PD-1 and PD-L1 inhibitors are in development and undergoing testing. These are also called monoclonal antibodies.
Depending on how fast the cancer is growing, where and how far it’s spread, and the patient's overall health, the care team also may recommend combining PD-1 with CTLA-4 inhibitors such as Yervoy® (ipilimumab). CTLA-4 inhibitors block a different protein on the T-cells so they can do their job.
The success rate of this combination of drugs is better than either alone. More than half (58 percent) of patients have seen their tumors shrink, according to the American Society of Clinical Oncology (ASCO). However, this combination may have more side effects.
Both PD-1 inhibitors and the PD-L1 inhibitor are given as an intravenous (IV) infusion. Typically, they require the IV to be given on a schedule of every two, three or four weeks.
Treatment may be stopped if the patient has serious side effects.
Ahead of treatment, the patient's doctor is likely to order blood tests to make sure the melanoma is able to be treated with these immunotherapy drugs.
Consider asking the care team these questions before starting PD-1 treatment:
Tell the doctor about any allergies to medications. No special diet is required beforehand.
The most common side effects from PD-1 inhibitors include:
Sometimes patients experience rarer side effects such as:
Immunotherapy may extend the lives of those whose melanoma is advanced and can’t be treated with surgery. Up to 45 percent of patients whose melanoma is inoperable or stage 4 have seen their tumors shrink when given the PD-1 inhibitors Keytruda® and Opdivo®, according to the ASCO.
A combination of chemotherapy and immunotherapy has been shown to be safe and appropriate for some patients with metastatic melanoma who haven’t responded to other treatments. While the patient may have greater side effects, combination therapies appear to increase the rate of response.