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Avelumab shows promise in Merkel cell carcinoma
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Avelumab, an anti–PD-L1 monoclonal antibody, induced sustained responses among patients with advanced chemotherapy-refractory Merkel cell carcinoma, according to data from an international phase 2 trial.
The agent also appeared well tolerated.
“No consensus on effective treatment for Merkel cell carcinoma exists,” Howard L. Kaufman, MD, of Rutgers Cancer Institute of New Jersey at Rutgers University, and colleagues wrote. “Multiple chemotherapy regimens have been used to treat patients with advanced disease, but responses are short-lived and relapse is common.”
Kaufman and colleagues conducted a multicenter, international, prospective, single-group, open-label phase 2 study that included 88 patients with stage IV Merkel cell carcinoma from 35 hospitals and cancer centers in North America, Europe, Asia and Australia.
Patients received 10 mg/kg avelumab (Pfizer) via IV every 2 weeks until disease progression, toxicity or other cause for withdrawal. Treatment with avelumab began July 25, 2014, and ended Sept. 3, 2015. Median follow-up was 10.4 months (interquartile range = 8.6-13.1).
Twenty-eight patients (31.8%; 95.9% CI, 21.9-43.1) achieved an objective response; this included 20 patients with partial responses and eight with complete responses. At the time of analysis, responses were ongoing in 23 patients (82%).
Four (5%) patients experienced a combined five grade 3 adverse events; these included two cases of lymphopenia and one case each of increased blood creatine phosphokinase, aminotransferase and blood cholesterol.
Serious adverse events included enterocolitis, infusion-related reaction, increase in aminotransferases, chondrocalcinosis, synovitis and interstitial nephritis (n = 1 for each). No grade 4 adverse events or deaths occurred during the study period.
“These data add substantial support to changing the therapeutic framework for the treatment of advanced Merkel cell carcinoma,” the researchers wrote.
The study’s findings were consistent with those of other trials, Axel Hauschild, MD, PhD, of the department of dermatology at University Hospital Schleswig-Holstein in Kiel, Germany, and Dirk Schadendorf, MD, of the department of dermatology at the Comprehensive Cancer Center at University Hospital Essen in Germany, wrote in an accompanying editorial.
“The results of Kaufman and colleagues’ study are strongly supported by results from other clinical trial data, including a phase 2 trial using the PD-1 blocking antibody pembrolizumab (Keytruda, Merck) in patients with advanced Merkel cell carcinoma,” they wrote. “Clinical trials to maximize synergistic benefits from combinations of checkpoint inhibitors — such as CTLA-4 antibodies, PD-1 antibodies, or PD-L1 antibodies — with or without radiotherapy should now be designed and executed. For the first time, there is some optimism on the horizon for treating patients with Merkel cell carcinoma, and hopefully this will also expand to other nonmelanoma skin cancers.” – by Andy Polhamus
Disclosures: Kaufman reports personal fees from Alkermes, Amgen, EMD Serono, Prometheus and Sanofi; nonfinancial support from Merck; and grants from Bristol-Myers Squibb outside of the submitted work. Please see the full study for a list of all other researchers’ relevant financial disclosures. Hauschild reports a consultant role with Merck Sharp & Dohme.
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