SITC Reacts to Approval of Pembrolizumab for Treatment of Metastatic Melanoma in Europe


The Society for Immunotherapy of Cancer is delighted that the European Commission has approved Merck & Co., Inc.’s pembrolizumab as a first-line treatment for patients with metastatic melanoma. Pembrolizumab is a monoclonal antibody that targets the programmed cell death 1 (PD-1) receptor on lymphocytes and offers a well-tolerated, cancer immunotherapy agent for patients combating this disease. This is the second immunotherapy approved in Europe as a treatment for melanoma in the past month alone.

“Melanoma remains a global public health threat and the approval of pembrolizumab for patients with metastatic melanoma in Europe represents an important advance in the field,” explained SITC President Howard L. Kaufman, MD, FACS (Rutgers Cancer Institute of New Jersey). “Pembrolizumab has demonstrated impressive response rates, which appear to be durable, and this approval allows patients suffering from advanced melanoma access to a potentially life prolonging drug much earlier in the course of their disease.”

According to Dr. Kaufman, “The incidence of melanoma is increasing more rapidly than other types of cancer. Historically, once the tumor spreads, melanoma patient survival rates have been typically less than one year. With the approval of immunotherapy agents, such as pembrolizumab, in the United States and abroad, we can anticipate longer life expectancies.” Dr. Kaufman added that “while pembrolizumab is approved in the United States, at present this is in the second line setting.” The European approval comes in advance of anticipated regulatory review of first-line pembrolizumab clinical trials in the United States.

How Pembrolizumab Works

Pembrolizumab targets the PD-1 receptor expressed on T cells. Normally, PD-1 functions to suppress T cell activity and pembrolizumab blocks this suppression allowing activated T cells to mediate tumor regression. Two PD-1 targeted agents, pembrolizumab and nivolumab, were approved by the U.S. Food and Drug Administration (FDA) for the treatment of advanced melanoma in 2014, with nivolumab receiving approval in Europe just last month.

About the Approval

The European Commission approval of pembrolizumab is based on the results of phase III trial KEYNOTE-006, a three-arm study to evaluate the safety and efficacy of two dosing schedules of pembrolizumab compared to ipilimumab for the treatment of ipilimumab-naïve participants with unresectable or metastatic melanoma. The first clinical trial to compare head-to-head two immune checkpoint inhibitors as front-line therapy for melanoma, KEYNOTE-006 revealed that pembrolizumab is superior to ipilimumab as first-line therapy.

At six months after treatment, progression-free survival was 45 percent for pembrolizumab arms and 26 percent for ipilimumab; overall survival (OS) for patients in the pembrolizumab arms was ~87 percent compared with 75 percent for those in the ipilimumab arm. Objective response rate was 33 percent for pembrolizumab arms and 12 percent for ipilimumab.

At 12 months after treatment, OS rates were 74 percent and 68 percent for the two pembrolizumab arms, respectively, compared to 58 percent for ipilimumab. Further, drug-related adverse events were lower in the pembrolizumab arms (12 percent) compared with the ipilimumab arm (20 percent).

What the Approval Means for Patients

“It is wonderful news for melanoma patients that another treatment option is now available as a standard choice in Europe,” explained SITC At-Large Director Jedd D. Wolchok, MD, PhD (Memorial Sloan Kettering Cancer Center). “Further, it is very gratifying to see additional evidence that another immunotherapy can extend survival in a challenging disease.”

As immunotherapies continue to demonstrate efficacy and safety in clinical trials, resulting in approvals in numerous countries across the globe, clinicians will have more tools—and patients strengthened capacities—to combat cancer.