As for squamous cell carcinoma, the drug of choice appears to be 1 of 2 FDA-approved, interchangeable PD-1 immune checkpoint inhibitors, which target proteins in the immune system that are ordinarily involved in restraining or turning off the body’s natural immune response. Of a handful of patients, 80% had durable responses up to 1 year, so far. No data results have yet been published.

The results of a small open-label trial in Merkel cell carcinoma, in which Dr Olencki participated, appeared in The New England Journal of Medicine.6 The study found that the use of the PD-1 immune checkpoint inhibitor, pembrolizumab (Keytruda), led to more durable responses in patients with advanced/metastatic disease than those typically seen in patients undergoing standard chemotherapy. None of the patients had received prior systemic therapy.

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“Merkel-cell cancers can go anywhere, any time,” Dr Olencki said, describing these rare cancers that afflict an estimated 2000 to 3000 patients in the United States each year.1 “This drug appears to work because it targets more cells with genetic mutations,” which are the hallmark of highly aggressive cancers.

Pembrolizumab already has FDA approval for the treatment of certain types of lung cancer and melanoma, and received attention last year when doctors successfully treated former President Jimmy Carter for his late-stage melanoma.

Whether this drug will gain approval for Merkel cell cancer treatment is uncertain. The 26-patient, open-label study showed that more than half of the patients on pembrolizumab had a “6-fold difference in how long responses lasted,” in contrast with chemotherapy, said Dr Nghiem, the study’s lead author.

At 1 year, 5% or less of patients treated with chemotherapy have not seen cancer progression, he said, while with pembrolizumab alone, “we’re seeing 45 percent” have no cancer progression.

Risk factors for Merkel cell cancer are similar to those for other skin cancers, including damaging exposure to ultraviolet rays, advancing age, and weakened immunity.1 In 2008, however, researchers identified a virus called Merkel cell polyomavirus as a cofactor that is present in roughly 80% of patients diagnosed with the disease.7

Treatment responses suggest that those who test positive for the virus might do better than those who lack it, although it’s not yet clear. “We hope the [future] data will be sufficiently compelling to change the way the disease is treated,” Dr Nghiem explained. Right now, not only do individuals with Merkel cell cancer not have FDA-approved options for treating their cancer, but there are no successful clinical trials even suggestive of a beneficial drug.

Pembrolizumab “shows us that our bodies have highly effective responses to cancer, which are being restrained,” he concluded. “’Pembro’ takes the brakes off and allows our bodies to do what nature intended them to do.”


  1. Skin Cancer Facts. American Cancer Society. Published April 13, 2015.
  2. Funding for Research Areas. National Cancer Institute. Published December 23, 2015.
  3. Skin Cancer (Including Melanoma) Research. National Cancer Institute.
  4. Sekulic A, Migden MR, Oro AE, Dirix L, Lewis KD, Hainsworth JD, et al. Efficacy and safety of vismodegib in advanced basal-cell carcinoma [published online ahead of print June 7, 2012]. N Engl J Med. doi: 10.1056/NEJMoa1113713.
  5. FDA approves new treatment for most common form of advanced skin cancer [news release]. Silver Spring, MD: U.S. Food and Drug Administration; July 24, 2015.
  6. Nghiem PT, Bhatia S, Lipson EJ, Kudchadkar RR, Miller NJ, Annamalai L, et al. PD-1 blockade with pembrolizumab in advanced merkel-cell carcinoma [published online ahead of print April 19, 2016]. N Engl J Med. doi: 10.1056/NEJMoa1603702.
  7. Feng H, Shuda M, Chang Y, Moore PS. Clonal integration of a polyomavirus in human merkel cell carcinoma. Science. 2008;319:1096-1100.