Advances in Personalized Therapies for Melanoma

Christine Wilson, cancer survivor, shares her experiences from the Abramson Cancer Center’s 2013- Focus Melanoma and CAN Prevent Skin Cancer Conferences. In this blog, she discusses advances in personalized therapy for melanoma patients.

Anyone who has attended all 10 of the Focus on Melanoma Conferences appreciates how much progress has been made in treating this disease over that span of time.

Paul Chapman, MD

In his keynote address, Paul Chapman, MD, of the Memorial Sloan-Kettering Cancer Center noted that in the 20th century—which somehow seems a long time ago—the five-year survival rate for patients with stage IV melanoma was 10 to 30 percent. That dismal picture began to change at the beginning of this century with the introduction of targeted therapies, notably vemurafenib and other agents that block the over expression of the BRAF gene, a mutation found in approximately 50% of melanoma patients.

The excitement surrounding these new therapies was tempered by the fact that over half of advanced melanoma patients did not benefit from them—and those that did often had responses that lasted an average of seven months as the melanoma became resistant and recurred.

A Change in Direction for Melanoma Research

In the last few years, the goal for researchers has been twofold:

• To find targeted agents that block other pathways that allow melanoma cells to grow and proliferate. These pathways can be either those that are activated when the tumor becomes resistant to the BRAF inhibitor—or parallel pathways found in patients who do not have the BRAF mutation.
• To find ways of activating the immune system to identify and fight melanoma cells.

Researchers have known for some time that melanomas are able to disable or even co-opt the body’s immune system to help the abnormal cells grow. One of the major advances in treating melanoma has been the introduction of ipilumimab—a targeted agent that activates T-cells to fight the cancer rather than affecting the tumor directly. For some patients, “ipi” has made an amazing difference.

Approximately 12 to 15 percent of these patients have a complete response to the treatment.

These patients rarely relapse and are considered cured. Others have long term progression free responses, but their disease returns.

The success of “ipi” has led to research to find other drugs that will activate the immune system to seek out and destroy melanomas. Phase I trials of anti-PD-1, an antibody that has been shown to shrink metastatic melanoma tumors are complete, and a phase III randomized trial to compare “ipi” with antiPD-1 or a combination of both agents will start soon.

Chapman summarized by saying:

• All melanomas should be checked for gene mutations
• Resistance is the key—but research is yielding new insights into the mechanisms of resistance, and with it, hope for improved therapies to overcome this problem.
• Several immunotherapy drugs are now in the development pipeline.
• New drug combinations, and new drug schedules are emerging, promising that the progress against melanoma will continue to be rapid and dramatic.

Penn Medicine's Melanoma and Pigmented Lesion Program was among the first in the country to provide information, evaluation, and genetic counseling for those at increased risk for melanoma and to create a model for melanoma screening. Learn more about Melanoma treatment and care at Penn Medicine.