June 2016, Vol. 5, No. 5
Pembrolizumab Elicits Response in Patients with Merkel Cell Carcinoma
Immunotherapy 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.
The following are a selection of key clinical trials that are currently recruiting patients for inclusion in investigations of new therapies or new combinations of available therapies for patients with colorectal cancer. Each clinical trial description includes the NLM Identifier to be used as a reference with ClinicalTrials.gov. The information [ Read More ]
If you can’t get your lung cancer patients to stop smoking, at least encourage them to exercise. That’s the message from research conducted on a huge cohort of individuals in the National Health and Nutrition Examination Survey (NHANES), showing that markers of inflammation were significantly reduced among male smokers with [ Read More ]