Immune Checkpoint Inhibitors May Benefit Patients With Merkel Cell Carcinoma

An experimental checkpoint inhibitor called avelumab may produce quick and durable responses in some patients with metastatic Merkel cell carcinoma, a rare, aggressive skin cancer with few effective treatments, according to results from a new phase II study published September 1, 2016, in Lancet Oncology. This is the second study to show a checkpoint inhibitor may benefit patients with Merkel cell carcinoma.

In the current phase II trial, 32% of patients with metastatic Merkel cell carcinoma experienced partial or complete shrinkage of their tumors when treated with avelumab, which is an anti-PD-L1 monoclonal antibody. Among patients whose tumors shrank, more than 90% sustained this response for at least 6 months.

For this phase II trial, researchers enrolled 88 patients from 35 cancer centers on four continents. All of the patients had already received at least one prior round of chemotherapy. Each participant received avelumab every other week until their cancer progressed or they experienced intolerable side effects. Avelumab was delivered intravenously at a dose of 10 mg/kg every 2 weeks.

Overall, 20 patients experienced tumor regression, and an additional eight saw their tumors disappear entirely. Almost 80% of patients responded to treatment in the first 6 weeks. At the time of the last patient follow-up assessment before publication, 27 of the 28 patients’ responses had lasted for at least 6 months, and six patients had responses that have lasted for at least a year. Unlike with chemotherapy, few patients experienced severe side effects and only two of the 88 patients discontinued treatment because of an adverse event.

The patients were treated between July, 2014, and Sept, 2015, and the median follow-up was 10.4 months. “The real story here isn’t even the response rate, it’s the durability, said study investigator Howard Kaufman, MD, of the Rutgers Cancer Institute of New Jersey, in a National Cancer Institute news release. “This is a uniformly fatal disease if it becomes metastatic, and the chemotherapy we have for it is pretty harsh.”

Researchers have found that the protein targeted by avelumab (PD-L1) is overexpressed by many Merkel cell tumors. In addition, most Merkel cell tumors are associated with a virus called Merkel cell polyomavirus, which integrates its DNA into a healthy cell’s DNA, compromising the immune response. For both reasons, researchers have been optimistic that immunotherapy might be effective against the disease.

Earlier this year, another phase II trial showed that pembrolizumab (Keytruda), which targets PD-1, is effective in Merkel cell carcinoma. In the avelumab trial, some patients responded even if their tumors didn’t overexpress PD-L1 or were not positive for the Merkel cell polyomavirus.  

Avelumab is not yet approved by the US Food and Drug Administration (FDA) for the treatment of any cancer. However, the FDA has granted it fast-track designation and orphan drug designation based on the results of this trial.