Retifanlimab-dlwr (Zynyz – Incyte), a programmed death receptor-1 (PD-1) blocking antibody, has received accelerated approval from the FDA for treatment of metastatic or recurrent locally advanced Merkel cell carcinoma (MCC) in adults. Accelerated approval of the drug was based on the response rate and duration of response. Retifanlimab is the third drug to be approved in the US for treatment of MCC; pembrolizumab (Keytruda), a PD-1 blocking antibody, is approved for the same indication as retifanlimab in patients ≥12 years old and avelumab (Bavencio), a programmed death ligand-1 (PD-L1) blocking antibody, is approved for treatment of metastatic MCC in patients ≥12 years old.

The FDA has approved avelumab (Bavencio – EMD Serono) and durvalumab (Imfinzi – AstraZeneca), two new immune check point inhibitors, and pembrolizumab (Keytruda – Merck), a checkpoint inhibitor that has been available in the US since 2014, for treatment of locally advanced or metastatic bladder cancer. Nivolumab (Opdivo) and atezolizumab (Tecentriq) were approved earlier for this indication.

The FDA has approved the fully-human programmed death ligand 1 (PD-L1) blocking antibody avelumab (Bavencio – EMD Serono/Pfizer) for treatment of metastatic Merkel cell carcinoma (MCC) in patients ≥12 years old. Avelumab is the first drug to be approved in the US for this rare skin cancer. About 1600 people in the US, most commonly older adults (mean age at presentation is 75 years), are diagnosed each year with MCC. Most of these patients can be treated with surgical resection, but ~50% will have a recurrence and >30% will eventually have metastatic disease. Median progression-free survival in patients with metastatic disease has been about 3 months with chemotherapy. MCC tumors, which often express PD-L1, have been treated offlabel with the PD-1 inhibitors pembrolizumab (Keytruda)1 and nivolumab (Opdivo).2

In an ongoing single-arm trial (JAVELIN Merkel 200), 88 patients with metastatic MCC (58 with PD-L1 positive tumors, 16 PD-L1 negative, 14 not assessable) who were previously treated with at least one chemotherapy regimen received at least one dose of avelumab; 75% of patients were 65 years or older. An objective response occurred in 28 patients (32%); 8 patients had a complete response. Tumor PD-L1 expression did not affect response rates. The duration of response was ≥6 months in 92% of responders.3

The most common adverse effects of avelumab in clinical trials were fatigue (50%), musculoskeletal pain (32%), diarrhea (23%), nausea (22%), rash (22%), and infusion-site reactions (22%). Serious treatment-related adverse events occurred in 6% of patients. Grade 3 or 4 adverse events (lymphopenia, elevation of creatine kinase, transaminase increases) occurred in 5% of patients. As with PD-1 inhibitors, immune-mediated adverse effects including pneumonitis, colitis, nephritis, hepatitis, and endocrinopathies (hypothyroidism, adrenal insufficiency, type 1 diabetes) can occur.

The recommended dosage of Bavencio is 10 mg/kg infused IV over 60 minutes every 2 weeks. The cost of one 10-mL vial containing 200 mg of the drug is $1504; three months' treatment for a 60-kg patient would cost $27,072.4

1. PT Nghiem et al. PD-1 blockade with pembrolizumab in advanced Merkel-cell carcinoma. N Engl J Med 2016; 374:2542.
2. K Mantripragada and A Birnbaum. Response to anti-PD-1 therapy in metastatic Merkel cell carcinoma metastatic to the heart and pancreas. Cureus 2015; 7:e403.
3. HL Kaufman et al. Avelumab in patients with chemotherapy-refractory metastatic Merkel cell carcinoma: a multicentre, single-group, open-label, phase 2 trial. Lancet Oncol 2016; 17:1374.
4. Approximate WAC. WAC = wholesaler acquisition cost or manufacturer's published price to wholesalers; WAC represents a published catalogue or list price and may not represent an actual transactional price. Source: AnalySource® Monthly. June 5, 2017. Reprinted with permission by First Databank, Inc. All rights reserved. ©2017. www.fdbhealth.com/policies/drug-pricing-policy.

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