Avelumab: First Drug Ever Approved for Merkel Cell Carcinoma

Zosia Chustecka


March 23, 2017

Today's approval of avelumab (Bavencio, EMD Serono) by the US Food and Drug Administration (FDA) is the first for a treatment of Merkel cell carcinoma (MCC), a rare and aggressive form of skin cancer.

 "While skin cancer is one of the most common cancers, patients with a rare form called Merkel cell cancer have not had an approved treatment option until now," said Richard Pazdur, MD, acting director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research and director of the FDA's Oncology Center of Excellence.

MCC is diagnosed in some 1600 people in the United States each year.  Although most patients present with localized tumors that can be treated with surgical resection, approximately half of all patients will experience recurrence, and more than 30% will eventually develop metastatic disease, the agency explains.  

Avelumab is a novel immunotherapy that acts an inhibitor of the programmed cell death (PD) pathway. MCC is the drug's first indication. It was granted an accelerated approval on the basis of response rates from a single-arm clinical trial conducted in 88 patients with chemotherapy-refractory MCC.

The FDA notes that 33% of these 88 patients experienced complete or partial shrinkage of their tumors. The response lasted for more than 6 months in 86% of responding patients and more than 12 months in 45% of responding patients.

That study, known as JAVELIN Merkel 2000, was published online September 1, 2016, in Lancet Oncology, as previously reported by Medscape Medical News.

"To our knowledge, this study is the largest trial of metastatic Merkel cell carcinoma ever reported," the study investigators commented. They explained that large, randomized studies in this patient population are difficult because Merkel cell carcinoma — an aggressive form of skin cancer — is a rare disease that has a rapid natural history and generally occurs in patients with substantial comorbidities.

"Achieving rapid, durable responses are difficult in this population of patients who have already progressed on chemotherapy," corresponding author Howard L. Kaufman, MD, associate director for clinical science at Rutgers Cancer Institute of New Jersey, New Brunswick, told Medscape Medical News at the time. "It is a significant advancement for avelumab to show an impact in this setting," he added

"These results in patients heavily pretreated with chemotherapy indicate that avelumab has a high potential to change clinical practice in this aggressive cutaneous malignancy," commented experts Axel Hauschild, MD, from the University Hospital Schleswig-Holstein, Kiel, Germany, and Dirk Schadendorf, MD, from the University Hospital Essen, Germany, in an accompanying editorial.

The editorialists went on to comment that avelumab, and also another PD inhibitor, pembrolizumab (Keytruda, Merck & Co), which also showed activity in a clinical trial, were "emerging as standard of care" for MCC.

The FDA noted that common side effects of avelumab include fatigue, musculoskeletal pain, diarrhea, nausea, infusion-related reactions, rash, decreased appetite, and peripheral edema. The most common serious risks are immune-mediated, wherein the body's immune system attacks healthy cells or organs, and may include pneumonitis, hepatitis, colitis, endocrinopathies, and nephritis. In addition, there is a risk for serious infusion-related reactions, and patients who experience these should stop therapy. The product should not be used in women who are pregnant or breast-feeding. 

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