Treatment for advanced melanoma continues to improve

March 2015

Treatment for advanced melanoma is changing rapidly. Breakthroughs in medical research are giving hope to patients who have melanoma that has spread.

Fueling this change is a type of treatment called targeted therapy. This therapy uses new drugs that can temporarily shrink the cancer. 

Breakthroughs in another type of treatment called immunotherapy, which helps the patient’s immune system fight cancer, also are helping some patients live longer.
“Just a few years ago, these treatments were unimaginable.”

 Abby S. Van Voorhees, MD, FAAD
Associate Professor of Dermatology, Hospital of the University of Pennsylvania

Advances in both targeted therapy and immunotherapy are continuing at a rapid pace. Many patients benefit from these treatments, and some appear to be cured.

The following explains how these new drugs, approved by the U.S. Food and Drug Administration (FDA) between 2011 and 2014, are helping patients. All have been approved to treat adults (18 years or older) who have melanoma that has spread.

Help the patient’s immune system fight the cancer

Ipilimumab (Yervoy®), which was FDA approved in 2011, is helping some people with advanced melanoma live longer. 

How ipilimumab works: This drug helps the patient’s immune system to recognize, target, and attack cancer cells. Healthy cells are left alone.

Patient responses to ipilimumab: In studies, patients had the following response:

  • This drug shrank tumors for about 11% of patients with advanced melanoma. 
  • Patients who respond often have a long-lasting response.
  • In patients who survive 7 years, the likelihood of a long-lasting response increases. No deaths have been reported in patients who live for 7 years after the first treatment.
  • It has been effective in patients when melanoma spreads to the brain. In 18% of these patients, the tumor(s) cleared, shrank, or did not progress.

Encouraging news: Giving patients ipilimumab and another drug that boosts the immune system can increase a patient’s response. In clinical trials, the patients receiving such combinations live longer and have fewer toxic side effects than patients who receive only ipilimumab. 

How to take ipilimumab: Patients receive IV drips at a hospital or cancer treatment center. 

Note: A medical oncologist (doctor who specializes in treating cancer) usually treats patients when melanoma spreads. This doctor can tell you how often you would take this drug and possible side effects. 

Pegylated interferon: Another advance in immunotherapy is the FDA approval of pegylated (or peg) interferon to treat melanoma that has spread to nearby lymph nodes. Peg-interferon causes fewer side effects than interferon given in the past. This may help patients take the drug for a longer time. The recommended treatment period is 5 years.

Target therapy can temporarily stop cancer from spreading

Cancer begins when changes take place within our genes. Your doctor may call these changes “gene mutations.” 

Some people with melanoma have changes to a specific gene called BRAF. Doctors often refer to this change as a “BRAF gene mutation.”

Researchers have developed drugs that can target a BRAF gene mutation. The following drugs are FDA approved to treat melanoma driven by a BRAF gene mutation:

  • Vemurafenib (Zelboraf®) approved in 2011
  • Dabrafenib (Tafinlar®) approved in 2013
  • Trametinib (Mekinist®) approved in 2013 
  • Dabrafenib + trametinib, approved 2014 

How these drugs works: If a patient has a certain BRAF gene mutation, these drugs can temporarily block the specific pathway that melanoma uses to grow. Because dabrafenib and trametinib block different parts of the same pathway, they can be more effective when taken together. 

Patient must have BRAF gene mutation: For a patient to receive this type of targeted therapy, the melanoma tumor must have a specific mutation in the BRAF gene. A tumor biopsy, which involves removing some of the melanoma and testing it, can tell your doctor whether you have a BRAF gene mutation.

Patient responses to these drugs: These drugs can shrink melanoma tumors and slow the progression of melanoma. In clinical trials, patients had the following response rates:

  • Dabrafenib: 54% have a positive response (tumors shrink or clear completely), which lasts about 5.6 months before the melanoma progresses. 
  • Trametinib: When a patient has a positive response, it lasts about 4.8 months before the melanoma progresses.
  • Dabrafenib + trametinib: 76% of patients have a positive response, which lasts about 9.4 months. 
  • Vemurafenib: More than half the patients had a positive response, which lasted about 6.7 months, and 6% of patients achieved a complete response (no sign of melanoma).

While these drugs can be effective, they tend to stop working in time. When the drug stops working, the melanoma can progress. At that time, other treatment options can be considered.

How to take these drugs: All of these drugs are pills. 

Note: A medical oncologist usually prescribes the pills and monitors patients. 

Since some of the side effects can occur in the skin, patients taking one of these drugs usually see a dermatologist for one year. 

Patients taking vemurafenib: Patients taking this drug must protect their skin from the sun because vemurafenib causes the skin to become extremely sensitive to sunlight. Spending just 5 minutes outdoors in the sun can cause sunburn. Patients also burn when they are outdoors in the shade.

Drugs that offer hope when other treatments fail 

In 2014, the FDA approved two drugs that can be considered when other treatments fail or stop working. Both nivolumab (Opdivo®) and pembrolizumab (Keytruda®) are FDA approved for patients who have:

  • Tried the drug ipilimumab 
  • A BRAF gene mutation 

Because some patients experience serious side effects, the FDA approved these drugs only for patients who have tried other treatment first. 

How nivolumab and pembrolizumab work: Like ipilimumab, these drugs enable the body’s immune system to attack the melanoma cells.

Research breakthroughs occurring at a rapid pace

Other treatments for advanced melanoma are being studied in clinical trials. More therapies are expected to be approved by the FDA.

More information about the newer FDA-approved therapies

If you are interested in exploring treatment options, you should ask your doctor which treatment might be a good fit for you.

Researchers continue to study the drugs discussed in this article. You can learn more about these drugs and look for clinical trials (run to improve drugs) that are accepting patients with advanced melanoma by clicking on the following pages:

References

American Academy of Dermatology, “New therapies giving hope for patients with advanced melanoma.” News release issued March 21, 2014.

Fox MC, Lao CD, et al. “Management options for metastatic melanoma in the era of novel therapies: a primer for the practicing dermatologist: part I: Management of stage III disease.” J Am Acad Dermatol. 2013 Jan;68(1)1.e1-1.e8.

Fox MC, Lao CD, et al. “Management options for metastatic melanoma in the era of novel therapies: a primer for the practicing dermatologist: part II: Management of stage IV disease.” J Am Acad Dermatol. 2013 Jan;68(1):13.e1-13e12.

Hinrichs CS, Rosenberg SA. “Exploiting the curative potential of adoptive T-cell therapy for cancer.” Immunol Rev. 2014 Jan;257(1):56-71

Hodi FS, Lee S, et al. “Ipilimumab plus sargramostim vs ipilimumab alone for treatment of metastatic melanoma: A randomized clinical trial.” JAMA. 2014 Nov 5; 312(17):1744-53.

Hodi FS, Corless CL, et. al. “Imatinib for melanomas harboring mutationally activated or amplified KIT arising on mucosal, acral, and chronically sun-damaged skin.” J Clin Oncol. 2013 Sep 10;31(26):3182-90.

Robert C, Long GV, et. al. “Nivolumab in previously untreated melanoma without BRAF mutation.” N Engl J Med. 2014 Nov 16. [Epub ahead of print.]

Thompson JF, Agarwala SS, et al. “Phase 2 Study of Intralesional PV-10 in Refractory Metastatic Melanoma.” Ann Surg Oncol. 2014 Oct 28. [Epub ahead of print]

U.S. Food and Drug Administration, “FDA approves Opdivo for advanced melanoma.” FDA news release issued December 22, 2014.

Van Voorhees AS, “From the editor: Dermatology is sitting at an interesting juncture.” Dermatology World. 2014; 24(5):2.
 
Wolchok JD, Kluger H, et al. “Nivolumab plus ipilimumab in advanced melanoma.” N Engl J Med 2013; 369:122-133. (Funded by Bristol-Myers Squibb and Ono Pharmaceutical; ClinicalTrials.gov number, NCT01024231.)