The US Food and Drug Administration (FDA) approved the checkpoint inhibitor avelumab as the first-ever treatment for metastatic Merkel cell carcinoma (MCC) in patients 12 years and older.
“The approval of avelumab for treatment of advanced MCC is a huge milestone for a patient population that has felt the burden of having a true ‘orphan’ disease,” Paul Nghiem, MD, PhD, the George F. Odland Chair in dermatology at the University of Washington and clinical director of skin oncology at the Seattle Cancer Care Alliance, told Cancer Therapy Advisor.
“The fact that MCC is about 3 times more likely to be lethal than an invasive melanoma has increased the stakes, and makes this approval even more significant for these patients,” added Dr Nghiem, an investigator of the JAVELIN Merkel 200 (ClinicalTrials.gov Identifier: NCT02155647) trial, from which the initial results were published in Lancet Oncology and on which the FDA’s accelerated approval was based.1
The avelumab trial is believed to be the largest prospective study ever for patients with metastatic MCC. This aggressive skin tumor is rare: up to 2000 new cases are diagnosed annually in the United States, compared with 87,000 for melanoma.2
Patients with metastatic MCC are generally older, have a poor prognosis, and are not candidates for surgery or radiotherapy. National guidelines note that chemotherapy rarely provides tumor control or a lasting remission and therefore cannot be supported as a standard of care. Five-year overall survival rates for patients with metastatic MCC range from 0% to 18%.3
JAVELIN Merkel 200 Results
The global 35-site, phase 2, single-arm JAVELIN Merkel 200 trial enrolled 88 patients with metastatic MCC treated with at least 1 prior chemotherapy regimen. Avelumab 10 mg/kg was administered intravenously over 1 hour every 2 weeks, and tumors were assessed by independent review every 6 weeks using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria.
Treatment with avelumab, a fully humanized IgG1 anti-PD-L1 antibody, resulted in an objective response rate of 33%, with 11% complete and 22% partial responses. Among the 29 patients who responded, duration of response ranged from 2.8 to 23.3+ months, with 86% of responses durable for 6 months or longer.
“Immunotherapy is a promising approach to a crucial unmet medical need,” the authors of the Lancet Oncology article wrote. “Our findings…provide evidence that these drugs are efficacious and safely administered in both treatment-naïve and chemotherapy-refractory settings. These data add substantial support to changing the therapeutic framework for the treatment of advanced Merkel cell carcinoma.”