Will September 4, 2014 become the day melanoma was vanquished forever?

Probably not. But it is the day the FDA approved a new drug that helps your immune system fight off this deadly cancer.

Pembrolizumab (brand name Keytruda), from Merck, got fast-track approval almost two months earlier than expected. The FDA gave approval without the usual three clinical trial phases because the drug showed amazing promise in Phase 1 trials.

Many patients with advanced melanoma saw tumors shrink and lived months longer than would normally be expected. Not all patients got the same benefits, and more studies need to be done to confirm the drug really does work that well.

What is Melanoma

Melanoma is a very serious skin cancer that starts in cells called melanocytes. These are the cells that give skin color by making a pigment called melanin. You get a tan because sun exposure causes them to make more melanin.

Skin cancer is the most common cancer in the US—about 3.5 million people are diagnosed every year. Less than 5% of those are melanoma—an estimated 76,100 cases will be diagnosed in 2014.

That’s the good news.

The bad news is melanoma is the deadliest of the skin cancers. It accounts for more than half of the skin cancer deaths each year. In 2014, about 13,000 people will die of skin cancer. Around 9700 of those will be from melanoma.

Pembrolizumab Helps the Body Kill Melanoma Cells

This newly approved therapy is an antibody that helps your immune system identify and kill cancer cells.

Keytruda targets a molecule that certain white blood cells (called T cells) use to figure out which cells need to die. This molecule is called programmed cell death 1 (PD-1). Cells with PD-1 signal the immune system to put on the brakes and let cells live. Certain kinds of tumors—including melanoma—have high levels of PD-1. So the body lets them live and grow.

Blocking this molecule with the Keytruda antibody essentially releases the brakes so the body can go about identifying and stopping the tumor cells.

The PD-1 pathway is a different target from the previously approved immunotherapy drug Yervoy (ipilimumab) from Bristol-Myers. That drug blocks a protein called CTLA-4.

Approved Only for Some Melanoma Patients

For now, the FDA has approved Keytruda only for the sickest patients who have no other treatment options.

These patients must have tried the above-mentioned Yervoy without getting better.

Also, if their tumors show a mutation called BRAF V600, they must also try a BRAF inhibitor. These patients can get Keytruda only after using both Yervoy and the BRAF inhibitor.

Patients who don’t get better with Yervoy or the Yervoy/BRAF inhibitor combination were basically out of options until now. Keytruda appears to help more than half of them stay alive for at least another year.

Unfortunately, like most cancer treatments, this one is expensive. There’s concern that the $150,000 per year price tag could leave many patients unable to afford it.

Trial Showed Significant Tumor Shrinkage

The work cited in the FDA news release involved 173 patients whose melanoma did not respond to ipilimumab (Yervoy). This group was divided into 2 groups, each receiving a different dose of the drug, either 2 mg/kg (the recommended dose) or 10 mg/kg. Both groups showed similar responses, with 24% of people seeing their tumors shrink.

These results were published in the Lancet on July 15, 2014.

The overall trial involved many more patients, not all of whom had taken ipilimumab. Overall results showed as many as 72% of patients showed some tumor shrinkage (but in some it was a very small response).

More work is needed to show that the treatment can actually improve survival and/or symptoms.

What’s Next for Pembrolizumab

Merck will still have to conduct Phase 2 and 3 clinical trials to verify that the drug not only shrinks tumors but helps people live longer and/or slows progression of melanoma.

Also, there’s some evidence that anti-PD-1 drugs can work in other cancers, including lung and bladder. The company is actually testing/planning to test the drug in patients with many different tumor types.

They’re also planning studies to see how it works in combination with other drugs. One of those studies involves an immunotherapy drug from Advaxis, ADXS-PSA. This drug targets prostate cancer and will be tested alone and as a combination treatment with pembrolizumab. The two companies plan to begin this study in 2015.