First-Line Avelumab in Metastatic Merkel Cell Carcinoma

Key Points

  • The response rate was 62% among patients with ≥ 3 months of follow-up and 71% among those with ≥ 6 months of follow-up.
  • Duration of response was ≥ 6 months in 83% of responders.

In a preplanned interim analysis of a phase II trial (JAVELIN Merkel 200 part B) reported in JAMA Oncology, D’Angelo et al found that avelumab was active in the first-line treatment of metastatic Merkel cell carcinoma. Avelumab was approved in March 2017 for treatment of patients aged ≥ 12 years with metastatic Merkel cell carcinoma on the basis of the JAVELIN Merkel 200 trial.

Study Details

In the study, 39 patients with no prior systemic treatment for metastatic disease enrolled as of March 2017 were treated with avelumab 10 mg/kg every 2 weeks until disease progression or unacceptable toxicity. Patients were unselected for programmed cell death-ligand 1 (PD-L1) expression or Merkel cell polyomavirus status.

Enrollment is ongoing. Response is being assessed by independent review committee using RECIST v1.1 criteria. The primary endpoint is durable response (objective response persisting for ≥ 6 months).

Response Rates

In the preliminary analysis, with median follow-up of 5.1 months, efficacy was assessed in 29 patients with ≥ 3 months of follow-up. The confirmed objective response rate was 62%, with complete response in 4 patients (14%); 14 (78%) of 18 responses were ongoing at the time of analysis. In patients with response, duration of response has been ≥ 3 months in 93% and ≥ 6 months in 83% (range = 1.2–8.3 months).  Among 14 patients with ≥ 6 months of follow-up, the confirmed objective response rate was 71%, with complete response in 4 patients. At the time of analysis, progression-free survival at 3 months was 67% and median progression-free survival was 9.1 months (range = 1.9 months–not estimable).

Adverse Events

Overall, treatment-related adverse events of any grade occurred in 72% of 39 patients, with grade 3 adverse events occurring in 21%. No treatment-related grade 4 adverse events or treatment-related deaths were observed. Treatment-related infusion-related reactions occurred in 23%.  Treatment-related adverse events such as cholangitis; elevated AST and ALT; paraneoplastic syndrome and gait disturbance; and paraneoplastic encephalomyelitis led to discontinuation of treatment in 6 patients (15%). Polyneuropathy was observed in 2 patients with infusion-related reaction.

The investigators concluded, “High rates of response to first-line avelumab therapy in patients with distant [metastatic Merkel cell carcinoma] build on previously reported antitumor activity after second-line or later treatment, and maturing progression-free survival data suggest that responses are durable. These data further support avelumab’s approval in the United States and European Union and use as a standard-of-care treatment for [metastatic Merkel cell carcinoma].”

The study was supported by Merck KGaA and is part of an alliance between Merck KGaA and Pfizer Inc.

Sandra P. D’Angelo, MD, of Weill Cornell Medical College and Memorial Sloan Kettering Cancer Center, is the corresponding author for the JAMA Oncology article. 

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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