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Immunotherapy appears better than chemotherapy for aggressive type of skin cancer

The first study of the immunotherapy drug pembrolizumab as the initial treatment for patients with a rare but aggressive form of skin cancer known as Merkel cell carcinoma reports better responses and longer survival than expected with conventional chemotherapy.

The study is the longest observation to date of the treatment of Merkel cell carcinoma patients with any anti-PD-1 immunotherapy drug in the first-line setting.

The findings, published in the Journal of Clinical Oncology, supported the recent U.S. Food and Drug Administration accelerated approval of pembrolizumab,  as a first-line treatment for adult and pediatric patients with advanced Merkel cell carcinoma.

In the 50-patient study of pembrolizumab as the initial treatment for patients with recurrent, locally advanced or metastatic Merkel cell carcinoma, more than half of the patients (28 patients, 56 percent) had long-lasting responses to the treatment, 12 of whom (24 percent) experienced a complete disappearance of their tumours.

Nearly 70 percent of patients in this study were alive two years after starting treatment.

"This is the earliest trial of immunotherapy as a front-line therapy for Merkel cell carcinoma, and it was shown to be more effective than what would be expected from traditional therapies, like chemotherapy," said Topalian, who is a Bloomberg~Kimmel professor of cancer immunotherapy at the Kimmel Cancer Center. "Immunotherapy provides an effective treatment for patients with Merkel cell carcinoma who before had few options. Immunotherapy is unique in cancer treatment, because it does not directly target cancer cells but rather removes constraints on the immune system's natural ability to find and destroy cancer cells."

The 50 patients in this study were treated at 13 centres across the United States in a clinical trial conducted by the Cancer Immunotherapy Trials Network.

Preliminary findings regarding the first 26 patients enrolled in the study were published in the New England Journal of Medicine in 2016.

The study was subsequently amended to add 24 more patients.

The National Institutes of Health (NIH) classifies Merkel cell carcinoma as an "orphan disease," as it is diagnosed in fewer than 2,000 people annually in the United States.

It typically occurs in older people and those who have suppressed immune systems.

About 80 percent of Merkel cell carcinomas are caused by a virus called the Merkel cell polyomavirus.

The remaining cases are attributed to ultraviolet light exposure and other, unknown factors.

In the study, treatment with pembrolizumab worked well against both virus-positive and virus-negative Merkel cell carcinomas, resulting in high response rates and durable progression-free survival in both subtypes.

The findings also showed that tumours expressing a PD-1-related protein called PD-L1 tended to respond longer to treatment, although patients whose tumours did not express PD-L1 also responded.

"These findings could be a precursor to developing more effective treatments for other virus-related cancers, which account for about 20 percent of cancers worldwide," said Sharfman, the Mary Jo Rogers Professor of Cancer Immunology and Melanoma Research.

The non-virus-related subtype is characterised by high numbers of genetic mutations in cancer cells, which has also been shown by the Bloomberg~Kimmel Institute group to be a biomarker of response in various cancers to checkpoint inhibitors such as pembrolizumab.

Pembrolizumab works against Merkel cell carcinoma by blocking PD-1, a molecule on the surface of immune cells that regulates immune responses, turning them on and off.

Cancer cells often manipulate PD-1 to send a "stop" signal to the immune system.

Blocking that signal with a checkpoint inhibitor, such as pembrolizumab, initiates a "go" signal, sending immune cells to attack cancer cells.

A protein on the surface of cancer cells, called PD-L1, is one mechanism cancer cells use to manipulate PD-1 and disrupt the immune response.

"Under the microscope, PD-L1 looks like an armour around the cancer cell," explained Taube, an associate professor of oncology, dermatology and pathology. "Pembrolizumab interrupts PD-1 signalling by blocking the communication between PD-1 and PD-L1, removing the stop signal and re-engaging the immune system to go after cancer cells."

Patients in this study received the immune checkpoint blocking drug pembrolizumab intravenously every three weeks for up to two years.

During this time, the status of their cancer was monitored periodically with imaging scans.

Overall, most patients tolerated the treatment well.

However, 28 percent of patients experienced serious side effects - including one treatment-associated death.

Source: Johns Hopkins Medicine

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European Cancer Organisation European Institute of Oncology

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Published by

ecancer Global Foundation