Anti–PD-1 Inhibitor Gains Foothold in Merkel Cell Carcinoma

Get Permission

Immunotherapy marches on! One of the latest frontiers for checkpoint inhibitors is the treatment of Merkel cell carcinoma, a rare but aggressive type of cancer.

First-line therapy with pembrolizumab (Keytruda)—an anti–PD-1 (programmed cell death protein 1) inhibitor—achieved an objective response rate of 56% in a phase II study of 26 patients with advanced Merkel cell carcinoma. Responses were achieved in patients with virus-positive and virus-negative tumors. The study was reported at the 2016 Annual Meeting of the American Association for Cancer Research (AACR)1 and published online in The New England Journal of Medicine2 to coincide with the ­presentation.

Paul Nghiem, MD, PhD

Paul Nghiem, MD, PhD

While the study is still ongoing, the vast majority [86%] who responded to pembrolizumab are still experiencing excellent disease control more than 6 months after starting therapy.
— Paul Nghiem, MD, PhD

Tweet this quote

“The objective response rate is similar to that of chemotherapy, but the duration of response to pembrolizumab appears to be significantly longer than that for chemotherapy,” said lead author Paul Nghiem, MD, PhD, Professor of Medicine, University of Washington School of Medicine and investigator at the Fred Hutchinson Cancer Research Center in Seattle. “While the study is still ongoing, the vast majority [86%] who responded to pembrolizumab are still experiencing excellent disease control more than 6 months after starting therapy,” he added.

Merkel cell carcinoma is an orphan disease related to ultraviolet exposure. In more than 80% of cases, polyomavirus is present. Although Merkel cell carcinoma responds to chemotherapy, responses are short-lived, and the disease is often aggressive. More than 40% of patients who develop it on the skin will develop advanced disease, with a median survival of less than 1 year.

There is currently no U.S. Food and Drug Administration (FDA)-approved therapy for advanced Merkel cell carcinoma. Chemotherapy with platinum/etoposide is the standard of care. Although patients commonly respond to therapy, responses are rarely durable. About 50% of cases progress by 3 months, and 90% progress by 10 months.

The rationale for use of pembrolizumab is to prime the immune system, which is characterized by “exhausted” T cells, Dr. Nghiem explained.

Study Details

The investigators conducted a single-arm, open-label, phase II trial of first-line therapy with pembrolizumab in 26 patients with unresectable or metastatic Merkel cell carcinoma. Pembrolizumab at 2 mg/kg was given every 3 weeks for up to 2 years. Twenty-six patients had at least one dose; 25 had at least 1 radiologic assessment. Median follow-up was 7.6 months.

The objective response rate among the 25 patients with at least one evaluation was 56%; 4 had a complete response, and 10 had a partial response. At a median follow-up of 33 weeks, relapses occurred in 2 of the 14 (14%) responding patients. Responses were ongoing in 12 of the 14 responders at the time of the presentation at the AACR Annual Meeting.

Tumor regression occurred in multiple organ sites and in patients with bulky disease, and regressions appeared to be durable, with response duration of up to 9.7 months. Dr. Nghiem said that by 3 months, it was evident which patients were responding. “Some responses were profound, some were partial, and in some patients, there was no effect [of pembrolizumab],” he told listeners.

The 6-month progression-free survival rate was 67%. Median progression-free survival was 9 months. Although not directly comparable, historical median progression-free survival for this disease is 3 months, added Dr. Nghiem.

Immunotherapy in Merkel Cell Carcinoma

  • Pembrolizumab achieved encouraging and durable responses in Merkel cell carcinoma, a rare but aggressive type of cancer with no currently approved standard therapy.
  • The presence or absence of polyomavirus and PD-L1 did not appear to be predictive of response.
  • Correlative studies are ongoing to try to identify responders.
  • These results may lead to accelerated approval for pembrolizumab in this orphan disease.

Of the 26 patients, 17 (65%) had virus-positive tumors. The objective response rate was 62% (10 of 16) among virus-positive tumors and 44% (4 of 9 patients) among virus-negative tumors.

PD-L1 status did not predict response, a finding that contrasts with reports on some other cancer types, Dr. Nghiem said.

Drug-related grade 3 or 4 adverse events were reported in 15% of patients. They were managed by discontinuation of pembrolizumab and initiation of glucocorticoid therapy as needed. This did not appear to affect the magnitude or duration of response.

Correlative studies are ongoing, and the trial will be expanded to include 24 additional patients.

Dr. Nghiem speculated that the response durability might lead to FDA approval for pembrolizumab in Merkel cell carcinoma. “We are hopeful,” he concluded. ■

Disclosure: Dr. Nghiem is a paid consultant for EMD Serono and has received support for biomarker studies for a clinical trial with Bristol-Myers Squibb.


1. Nghiem PT, Bhatia S, Lipson E, et al: Clinical activity, immune and viral correlates of PD-1 blockade with pembrolizumab as first systemic therapy in patients with advanced Merkel cell carcinoma. 2016 AACR Annual Meeting. Abstract CT096. Presented April 19, 2016.

2. Nghiem PT, Bhatia S, Lipson EJ, et al: PD-1 blockade with pembroblizumab in advanced Merkel-cell carcinoma. N Engl J Med. April 19, 2016 (early release online).

Related Articles

Expert Point of View: Winald Gerritsen, MD, PhD

Winald Gerritsen, MD, PhD

Winald Gerritsen, MD, PhD

“This is a really great study with excellent translational research,” said formal discussant Winald Gerritsen, MD, PhD, Professor of Immunotherapy at Radboud University Medical Center, Nijmegen, The Netherlands. “I consider it practice-changing for Merkel cell...