The Japanese Ministry of Health, Labor and Welfare has approved avelumab (Bavencio) for use in patients with metastatic Merkel cell carcinoma, according to Merck KGaA.
Naoya Yamazaki, MD, PhD
The Japanese Ministry of Health, Labor and Welfare has approved avelumab (Bavencio) for use in patients with metastatic Merkel cell carcinoma (MCC), according to Merck KGaA and Pfizer, the co-developers of the PD-L1 inhibitor.
Avelumab is the first curative treatment for unresectable MCC and the first anti—PD-L1 agent approved in Japan.
"Until now, there were no licensed treatments for MCC in Japan," Naoya Yamazaki, MD, PhD, chief of the department of dermatologic oncology, National Cancer Center Hospital, Japan, said in a press release. "As a cancer that progresses quickly and has, for so many, a poor prognosis, today's approval is a huge step forward for people impacted by this destructive disease."
MCC, also known as neuroendocrine carcinoma of the skin or trabecular cancer, is a designated rare disease in Japan and is estimated to affect fewer than 100 patients. It is an aggressive disease in which cancer cells form in the top layer of the skin, close to nerve endings. MCC often starts in those areas of the skin that are most often exposed to the sun, including the head and neck, and arms.
The ministry previously awarded Orphan Drug Designation to avelumab in December 2016. The agent was approved for MCC in the United States in March and in Europe earlier this month. In a press release, Pfizer noted that this is the first Asian country to approve avelumab.
The approval is based on data from the phase II JAVELIN Merkel 200 study. In Part A of the open-label trial, the objective response rate (ORR) with avelumab was 33% (95% CI, 23.3-43.8), which included an 11.4% (95% CI, 6.6-19.9) complete response (CR) rate and a 21.6% (95% CI, 13.5-31.7) partial response (PR) rate.1,2 The duration of response (DOR) was at least 6 months in 93% of the responding patients, with 71% having a DOR of 12 months or more.3 DOR ranged from 2.8 months to more than 24.9 months.3
Part A of the JAVELIN Merkel 200 study enrolled 88 previously treated patients with metastatic MCC.1,2 The median age of patients in the study was 72.5 years, and each received avelumab at 10 mg/kg every 2 weeks. Patients had received at least 1 prior therapy (59.1%), with 11.4% having ≥3 prior system treatments. Most patients in the study were male (73.9%) and the ECOG performance status was 0 (55.7%) and 1 (44.3%).
The most common site of primary tumor was the skin (76.1%) and all patients had metastatic involvement at the time of study entry. Visceral disease was present for 53.4% of patients. Overall, 65.9% of patients were PD-L1-positive and 52.3% were positive for the Merkel cell polyomavirus (MCPyV). Eight percent of patients were negative for both PD-L1 and MCPyV and 40.9% were positive for both markers.
Median progression-free survival (PFS) with avelumab was 2.7 months (95% CI, 1.4-6.9). The 6-month PFS rate was 40%. The median overall survival (OS) was 11.3 months (95% CI, 7.5-14.0) and the 6-month OS rate was 69%.
The ORR was 34.5% in the PD-L1-positive arm and 18.8% in the PD-L1-negative group. The response rate in those who were not evaluable for PD-L1 status was 35.7%. The ORRs were 26.1% and 35.5% in the MCPyV-positive and -negative arms, respectively. In those not evaluable for the virus the ORR was 45.5%. Patients who were positive for both markers had an ORR of 30.6% and those negative for both markers had an ORR of 28.6%.
Part B of the JAVELIN Merkel 200 study included 39 patients with metastatic MCC who had not received prior systemic therapy in the metastatic setting.3 The ORR was 62% in these patients, comprising a CR rate of 14% and PR rate of 48%. The 3-months PFS rate was 67%.
The safety data the EC considered included 1738 patients with solid tumors—88 with metastatic MCC—who received avelumab at 10 mg/kg every 2 weeks.3 The most common all-grade adverse events (AEs) were fatigue (32.4%), nausea (25.1%), diarrhea (18.9%), decreased appetite (18.4%), constipation (18.4%), infusion-related reactions (17.1%), weight decrease (16.6%), and vomiting (16.2%). Grade ≥3 AEs that were most commonly reported included anemia (6.0%), dyspnea (3.9%), and abdominal pain (3.0%). Serious AEs included immune-related AEs and infusion-related reactions.