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Avelumab induces durable responses in advanced Merkel cell carcinoma
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CHICAGO — Treatment with avelumab produced durable responses in patients with metastatic Merkel cell carcinoma who experienced progression after chemotherapy, according to phase 2 study results presented at the ASCO Annual Meeting.
“These data ... support the fact that Merkel cell carcinoma may be a tumor that is amenable to immunotherapy,” Howard L. Kaufman, MD, FACS, chief surgical officer and chief of the division of surgical oncology at Rutgers Cancer Institute of New Jersey, and professor of surgery at Robert Wood Johnson Medical School, said during his presentation.
Howard L. Kaufman
Merkel cell carcinoma is an aggressive form of skin cancer associated with Merkel cell polyomavirus. Few therapeutic options exist for patients with metastatic disease who progress after first-line chemotherapy.
Merkel cell carcinoma tumors frequently express PD-L1 in the tumor microenvironment on tumor and immune cells.
Avelumab (MSB0010718C; Pfizer, Merck KGaA), an anti–PD-L1 fully human monoclonal antibody, received FDA breakthrough therapy designation for the treatment of Merkel cell carcinoma. The agent also has demonstrated efficacy in multiple cancers.
Kaufman and colleagues studied single-agent avelumab in a cohort of 88 patients (median age, 72.5 years; range, 33-88; 74% men) with metastatic Merkel cell carcinoma who progressed after chemotherapy.
Researchers assigned patients to 10 mg/kg biweekly avelumab until confirmed progression, unacceptable toxicity or withdrawal. They assessed tumors by RECIST criteria every 6 weeks.
Overall response rate served as the primary endpoint. PFS, safety and tolerability, and duration of response served as key secondary endpoints.
Kaufman reported data on a subgroup of 61 patients followed for at least 24 weeks. This cohort had an ORR of 32% (n = 18; 95% CI, 18.5-42.6), with six complete responses achieved.
Twelve patients achieved partial responses, with seven patients achieving stable disease. Fifteen responses remained ongoing at the time of reporting, with duration of response ranging from 2.8 months and greater to 14.6 months (median not reached).
The majority of responses (n = 14) were achieved by week 7. The median time to response was 6 weeks, and the cohort had a 6-month durable response rate of 29.1%.
Thirty-six percent of patients had confirmed progressive disease. Eighteen patients could not be evaluated due to lack of a confirmatory CT scan.
The cohort had a median PFS of 2.7 months (95% CI, 1.4-4.2), with a 6-month PFS rate of 40% (95% CI, 23-49).
Frequently occurring treatment-related adverse events included fatigue (21.6%) and infusion-related reactions (13.6%). Grade 3 adverse events occurred in 3 patients; the researchers did not record any grade 4 adverse events or treatment-related deaths.
“Avelumab offers a new treatment option for patients with this disease,” Kaufman said. “The recent advances with PD-L1– and PD-1–targeted agents has an opportunity to change the standard of care for patients with this disease.” – by Cameron Kelsall
Disclosure: Kaufman reports honoraria from, and consultant and speakers bureau roles with, Merck, as well as honoraria, research funding and travel expenses from multiple pharmaceutical companies. Please see the abstract for a list of all other researchers’ relevant financial disclosures.
Perspective
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Suzanne Topalian, MD
Merkel cell carcinoma is a rare but aggressive skin cancer for which no effective treatments have been available, until recently. Following on the heels of a publication in The New England Journal of Medicine, in which researchers reported a 56% response rate in Merkel cell carcinoma treated with the anti–PD-1 therapy pembrolizumab (Keytruda, Merck) in the first-line setting, the current study by Kaufman and colleagues demonstrates the efficacy of the anti–PD-L1 drug avelumab (MSB0010718C; Pfizer, Merck KGaA) in this disease.
The researchers report an objective response rate of 32% in patients with Merkel cell carcinoma who had not responded to prior therapies, including 9% complete responses. Although the observation period was relatively short, with a median of 10 months, responses appeared to be durable and most were ongoing at the time of analysis.
Although the median patient age in this study was 73 years — which is typical of patients with Merkel cell carcinoma — anti–PD-L1 therapy was generally well-tolerated. Treatment was effective in both Merkel cell polyomavirus-associated and virus-negative tumors.
Thus, the PD-1/PD-L1 pathway appears to be an important target for Merkel cell carcinoma therapy. Continued follow-up and additional clinical testing will be needed to reveal the true impact of these therapies on long-term survival in this disease.
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