Efficacy of Avelumab in Newly Diagnosed Metastatic Merkel Cell Carcinoma

Merkel cell carcinoma (MCC) is a rare but aggressive skin cancer with few treatment options and poor prognosis, particularly in patients with metastatic disease. Until recently, chemotherapy was the only first-line treatment option. Despite high initial responses to chemotherapy, responses are usually of a short duration (2.8 months – 8 months), and chemotherapy is associated with substantial toxicity. Immune checkpoint blockade with PD-1/PD-L1 inhibitors is associated with clinical activity and durable responses in patients with advanced MCC. The PD-L1 inhibitor avelumab became the first treatment approved for metastatic MCC based on results from the JAVELIN 200 trial. According to a recent update in previously treated MCC (part A of the study), an estimated 74% of responses with avelumab lasted more than one year, and median survival was 12.9 months.

In a preplanned interim analysis from part B of the ongoing JAVELIN Merkel 200 study examining avelumab in treatment-naïve patients with metastatic MCC, safety was assessed in 39 patients, while efficacy was evaluated in 29 patients, with at least 3 months of follow-up. The confirmed objective response rate (ORR) was 62.1%, including complete response in 13.8% of patients. Among responders, 93% had a duration of response (DoR) of at least 3 months and 83% had a DoR of at least 6 months. Responses were still ongoing in 77.8% of patients at the time of this analysis. Median progression-free survival (PFS) was 9.1 months.

Adverse events (AEs) were consistent with the known safety profile of avelumab. Grade 3 AEs occurred in 20.5% of patients, and there were no grade 4 AEs or treatment-related deaths. Grade 1 immune-related AEs occurred in 15.4% of patients.

The investigators concluded that this interim analysis confirms the safety and clinical activity of avelumab monotherapy in previously untreated metastatic MCC and supports its use as a standard of care in this setting. However, longer follow-up is needed to determine the overall survival benefit. Two other checkpoint inhibitors, nivolumab and pembrolizumab, are also being evaluated as first-line treatment options for metastatic MCC.

JAMA Oncol. 2018 March 22. [Epub ahead of print].


Clinical Opinion Poll

When would you recommend dabrafenib + trametinib combo for a patient with advanced, symptomatic, PD-L1–low, lung adenocarcinoma and BRAF V600 mutation?