Durable Responses Reported With Avelumab in Chemotherapy-Refractory Metastatic Merkel Cell Carcinoma
In a phase II trial reported in The Lancet Oncology, Kaufman et al found that the anti–PD-L1 (programmed cell death ligand 1) monoclonal antibody avelumab produced durable responses in patients with stage IV Merkel cell carcinoma progressing after cytotoxic chemotherapy.
Study Details
In the study, 88 patients from 35 sites in North America, Europe, Australia, and Asia received avelumab intravenously at 10 mg/kg every 2 weeks. The primary endpoint was confirmed objective response on RECIST (Response Evaluation Criteria in Solid Tumors) version 1.1 assessed by an independent review committee. All patients had received at least one previous line of systemic therapy, including at least one for metastatic disease, and 41% had received at least two previous lines of therapy. The primary site was the skin in 76%. Tumors were positive for PD-L1 expression in 66% and for Merkel cell polyomavirus in 55%.
Responses
Median follow-up was 10.4 months. Median duration of treatment was 17 weeks. Objective response was observed in 28 patients (31.8%, 95.9% confidence interval [CI] = 21.9%–43.1%), including complete response in 8 patients (9%) and partial response in 20 patients (23%); stable disease was observed in 9 patients (10%). Response was achieved in 34.5% of programmed cell death protein 1 (PD-1)–positive patients and 18.8% of PD-1–negative patients and in 26.1% of polyomavirus-positive and 35.5% of polyomavirus-negative patients.
Responses were ongoing in 23 of 28 responders (82%) at the time of analysis. The proportion of responses with duration ≥ 6 months was 92%, with duration ranging from 2.8+ to 17.5+ months, and median duration had not been reached. Responses were observed at first tumor assessment at week 7 in 22 responders (79%).
Adverse Events
Grade 3 treatment-related adverse events were observed in four patients (5%), consisting of lymphopenia in two, increased creatine phosphokinase in one, increased aminotransferase in one, and increased cholesterol in one. Serious treatment-related adverse events occurred in five patients (6%), consisting of enterocolitis, infusion-related reaction, increased aminotransferases, chondrocalcinosis, synovitis, and interstitial nephritis. Treatment was discontinued due to adverse events in two patients (2%). There were no treatment-related deaths.
The investigators concluded: “Avelumab was associated with durable responses, most of which are still ongoing, and was well tolerated; hence, avelumab represents a new therapeutic option for advanced Merkel cell carcinoma.”
The study was funded by Merck KGaA.
Howard L. Kaufman, MD, of Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey, is the corresponding author of The Lancet Oncology article.
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