New era looming MCC treatment
Immune checkpoint inhibitors generating promising results in clinical trials
The international, multicenter phase 2 study of avelumab for treatment of chemotherapy-resistant metastatic MCC enrolled 88 patients with stage IV disease. Forty percent of patients had received at least two prior systemic anticancer treatments and about half of the patients had visceral disease.
Avelumab 10 mg/kg was administered as an intravenous infusion every two weeks. Confirmed objective response was assessed as the primary endpoint, and after a median follow-up of 10.4 months, it was achieved by 28 (31.8%) patients, of which eight benefited with a complete response and 20 had a partial response. Two of the eight patients with a complete response had visceral disease.
At the time of the data analysis, 23 patients had an ongoing objective response, and 92% of responses were durable for at least six months.
“Seeing objective responses in treatment-resistant MCC is truly remarkable, and whereas median progression-free survival with chemotherapy is only about three months, some patients with complete responses are remaining disease-free for over one year,” Dr. Brownell says.
Inclusion criteria required patients to be immune-competent. There were no criteria regarding PD-L1 expression or Merkel cell polyomavirus status, and in subgroup analyses, neither of those characteristics predicted response to avelumab.
The study investigating pembrolizumab as first-line therapy enrolled 26 patients who were treated with a dose of 2 mg/kg every three weeks. After a median follow-up of 7.6 months (range 7 to 53 weeks), 14 (56%) of 25 evaluable patients demonstrated an objective response, of which four were complete responses. Response duration ranged from at least 2.2 months to at least 9.7 months. Again, PD-L1 expression and Merkel cell polyomavirus status did not predict treatment response.
“The higher response rate in this study may be explained by the fact that patients treated in the first-line setting may have less advanced disease and less resistant tumors. It will be interesting to see what the objective response rate is with avelumab as first-line treatment for advanced MCC, but definitive understanding of the relative efficacy of anti-PD-L1 versus anti-PD-1 treatment would require a head-to-head trial of the two strategies,” Dr. Brownell says.
Both avelumab and pembrolizumab have been well-tolerated in patients with MCC, and their side effect profiles are consistent with the adverse events associated with pembrolizumab treatment in patients with melanoma.
“Unlike conventional chemotherapy that causes cytotoxic side effects, immune checkpoint inhibitors primarily cause immune-related adverse events. With appropriate safety monitoring, however, autoimmune events such as colitis, pneumonitis, and hypophysitis, are being recognized early and treated promptly so that they are less likely to become severe,” Dr. Brownell says.
Disclosures: Dr. Brownell reports no relevant financial interests to disclose. Dr. Brownell’s opinions are his own and do not necessarily represent the official views of the NIH.
1. Kaufman HL, Russell J, Hamid O, et al. Avelumab in patients with chemotherapy-refractory metastatic Merkel cell carcinoma: a multicentre, single-group, open-label, phase 2 trial. Lancet Oncol. 2016;17(10):1374-1385.
2. Nghiem PT, Bhatia S, Lipson EJ, et al. PD-1 blockade with pembrolizumab in advanced Merkel-cell carcinoma. N Engl J Med. 2016 30;374(26):2542-2552.