Melanoma: Fertile Territory for the Development of New Treatments

In clinical trials, melanoma remains a ripe discovery ground for the application and combination of immunotherapies and targeted drugs.

LAURA KENT took a combination of two immunotherapies in a clinical trial, and now has no evidence of her recurrent melanoma. - PHOTO BY MICHAEL CRABB
LAURA KENT took a combination of two immunotherapies in a clinical trial, and now has no evidence of her recurrent melanoma. - PHOTO BY MICHAEL CRABB
After Laura Kent learned that a mole on the back of her left arm was cancerous in May 2014, she endured three surgeries to remove it, along with several nearby lymph nodes. Through all of that, the cancer kept coming back. Kent’s tumor tested positive for one of the BRAF mutations that is now treatable with targeted anti-cancer drugs, but her doctors at Fox Chase Cancer Center in Philadelphia thought she might do even better on a treatment that would prompt her own immune system to eliminate the cancer.

So, under the care of medical oncologist Anthony Olszanski, in January 2015, Kent was entered into a trial of two immunotherapy treatments: Imlygic (talimogene laherparepvec), a genetically modified form of the herpes virus, and Keytruda (pembrolizumab), which targets the immune-suppressing protein PD-1. The Imlygic was injected directly into her melanoma lesion, and then, a few hours later, she received an infusion of Keytruda.

After three doses of the combination treatment, which Kent received every other week, her melanoma disappeared. “That was when I knew I would not die from this cancer,” says Kent, 39, who lives in Harrisburg, Pennsylvania.

Kent expected to keep taking Keytruda for a full year, but the drug caused her to develop joint pain, a possible consequence of this and other treatments that alter the immune system. But her oncologists couldn’t find any sign of her cancer anyway, so they took her off all treatments. Six months later, she is still cancer-free — and grateful she was able to get there without chemotherapy.

“If I had chemo, my quality of life would have been really bad,” she says. “And the cancer more than likely would have come back. The fact that [the combination] got rid of the cancer so quickly was just a godsend.”

Melanoma remains a fertile territory for the development of new, highly effective therapies — particularly drugs that stimulate the immune system to fight off the cancer. Imlygic, for instance, was approved by the U.S. Food and Drug Administration in October of 2015, and Keytruda was approved in September 2014 as a second-line drug and then in December 2015 for first-line use.

At the same time, researchers are discovering new mutations in melanoma and developing drugs to target them. Targeted treatments that have already been approved have improved the prognosis for patients who test positive for the BRAF mutations known as V600E and V600K, so now research teams all over the country have launched hundreds of clinical trials, testing not only new targeted treatments but cocktails of these drugs in combination with immunotherapies that might someday reverse the poor outcome for patients who would have run out of options just a few years ago.

Although responses to newer treatments still tend not to be permanent, there’s good cause for enthusiasm in this cancer type. “It’s very exciting times for melanoma,” says Anthony Olszanski, associate professor in the department of hematology/oncology at Fox Chase Cancer Center. “There’s good reason for patients to be in trials and good reason to have more hope for our patients.”


The Imlygic/Keytruda combination trial is generating excitement among oncologists because of the potential of these drugs, each approved as a single agent, to work together to capitalize on two different methods for activating the immune system. Imlygic is what’s known as an oncolytic virus: It has a natural ability to kill cancer cells, but it is also specially engineered to include a protein called granulocyte macrophage colony-stimulating factor (GM-CSF), which attracts immuneboosting cells to the tumor. Keytruda works differently, because it inhibits the PD-1 “checkpoint” that can be activated in some cancers, preventing the immune system from recognizing and attacking cancer cells.

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