PD-1 blockers and melanoma

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 your immune system so that it finds and attacks cancer cells.

Your 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 your 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.

PD-1 inhibitors

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 your 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.

PD-L1 inhibitor

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 your 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 your body and the BRAF mutation is present. (About half of all melanoma cells have this mutation that helps it grow.) Those other drugs that may be used in combination are Cotellic^® (cobimetinib) and Zelboraf^® (vemurafenib).

Other PD-1 and PD-L1 inhibitors are in development and undergoing testing. These are also called monoclonal antibodies.

PD-1 and CTLA-4 inhibitors

Depending on how fast your cancer is growing, where and how far it’s spread, and your overall health, your care team also may recommend combining PD-1 with CTLA-4 inhibitors such as Yervoy^® (ipilimumab). CTLA-4 inhibitors block a different protein on your 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.

What to expect

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.

• Keytruda^® is given in 30-minute infusions every three weeks.
• Opdivo^® is given in 30-minute infusions every two weeks, or every four weeks at a higher dosage.
• Tecentriq^® is given in 30-minute infusions every two, three or four weeks depending on the dosage. The first infusion may be 60 minutes.

Treatment may be stopped if you have serious side effects.

How to prepare for your treatment

Ahead of treatment, your doctor is likely to order blood tests to make sure the melanoma is able to be treated with these immunotherapy drugs.

Consider asking your care team these questions before starting PD-1 treatment:

• Why do you recommend this type of immunotherapy for me?
• What other treatments may I be getting? Or will this be my only treatment?
• How and where am I receiving this treatment?
• What do I need to do to get ready for this treatment?
• How will it make me feel?
• Whom do I call if I have questions or problems once treatment starts?

Tell your doctor if you have any allergies to medications. No special diet is required beforehand.

Risks and side effects

The most common side effects from PD-1 inhibitors include:

• Fatigue
• Rash
• Diarrhea
• Nausea
• Itchy skin
• Poor appetite
• Constipation
• Joint pain

Sometimes patients experience rarer side effects such as:

• Changes in the color of skin
• Cough and chest pain
• Muscle weakness and numbness
• Trouble breathing
• Hepatitis (liver damage)
• Myocarditis (inflammation of the heart muscle)
• Overactive or underactive thyroid

Benefits of PD-1 inhibitors

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 you may have greater side effects, combination therapies appear to increase the rate of response.