June 2016, Vol. 5, No. 5

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Pembrolizumab Elicits Response in Patients with Merkel Cell Carcinoma

AACR

Nghiem98pxImmunotherapy with the programmed death 1 (PD-1) inhibitor pembrolizumab induced durable responses in a phase 2 clinical trial of a virus-related cancer. Among 26 patients with Merkel cell carcinoma (MCC) treated in the trial, 12 of 14 patients (86%) who responded to pembrolizumab have ongoing responses after a median follow-up of 7.6 months, and the objective response rate (ORR) was 62% in patients with virus-positive tumors, reported Paul Nghiem, MD, PhD, at the American Association for Cancer Research Annual Meeting.

Currently, no drugs are approved to treat MCC. Typically, platinum-based chemotherapy serves as first-line treatment of MCC, and although the ORR to chemotherapy is about 55%, these responses are transient, said Dr Nghiem, Professor of Medicine, Division of Dermatology, University of Washington School of Medicine, Seattle.

The Merkel polyomavirus (MCPyV) drives about 80% of MCC cases. More than 40% of patients with MCC develop advanced disease within 3 months of initiating chemotherapy, and 90% will have disease progression by 10 months. Median survival is just 9.5 months after a diagnosis of metastatic MCC.

The rationale for testing pembrolizumab in MCC is that PD-1 on the T cells has been shown to be present in MCPyV-specific T cells in up to two-thirds of patients with virus-positive MCC.

The single-arm, open-label trial that Dr Nghiem presented here included 26 patients with advanced/metastatic MCC who had received no prior systemic therapy. Seventeen of the 26 patients had MCPyV-positive disease. All patients received pembrolizumab 2 mg/kg every 3 weeks, with response assessed every 9 to 12 weeks.

At the time of data analysis, treatment duration with pembrolizumab was 9 to 49 weeks. The ORR was 56% in all patients enrolled. The response rate is higher than that seen with PD-1 inhibitors in the treatment of other solid tumors. “Maybe that’s because historically, this has been a very immune-associated cancer,” Dr Nghiem said. “Viral status is a very interesting story and an evolving one.” Of the 16 patients with MCPyV-positive tumors, 62% had responses, compared with 44% of the 9 patients with virus-negative tumors. “That was not a statistically significant difference between the virus-positives and -negatives, but maybe suggests…there may be a better story there for virus positives,” he said.

“We believe that the immune system is likely ‘seeing’ different targets in the virus-positive and virus-negative patients,” he said. Virus-positive tumors produce viral proteins required for tumor growth, and these viral proteins may be recognized by the immune system. In contrast, virus-negative MCC has extremely high numbers of mutations caused by ultraviolet exposure and is more likely to be recognized by the immune system.

Four patients had a complete response, 3 of whom had virus-positive disease, and 10 patients had a partial response, 7 of whom had virus-positive disease.

Responses were already evident by the first scan at 3 months, and many of these responses were “profound,” said Dr Nghiem. Responses are ongoing in 12 of 14 patients (86%).

The median progression-free survival (PFS) was 9 months compared with a historical median PFS of about 3 months for MCC patients treated with chemotherapy, he said. The median 6-month PFS was 67%.

An additional 24 patients are being recruited into the trial to confirm the results.

Adverse events in this trial were similar to those observed in other anti–PD-1 trials and were largely managed with corticosteroid treatment and drug cessation. Responses are ongoing in 2 patients in whom pembrolizumab was discontinued for toxicity.

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