Effective treatments for aggressive Merkel cell carcinoma that go beyond PD-1/PD-L1 checkpoint therapies are needed to stabilize disease and further improve prognosis for patients with this rare form of skin cancer, according to an article published in Dermatologic Therapy.

Merkel cell carcinoma, which is linked to ultraviolet light and exposure to the Merkel cell polyomavirus, is characterized by painless and rapidly enlarging nodules on the skin. Immunotherapies via blockade of the PD-1/PD-L1 pathway have become a treatment option for this carcinoma, particularly in its advanced stages. Avelumab, pembrolizumab, and nivolumab are examples of immunotherapies used for the management of Merkel cell carcinoma. Despite the promising efficacy of these therapies for this patient population, their ability to induce remission and stabilize disease is often limited to only half of patients with this carcinoma.

Other treatments that modulate the antitumor response are under investigation for Merkel cell carcinoma. Talimogene laherparepvec, for example, is a genetically modified oncolytic herpes simplex virus type 1 that has demonstrated potentially promising responses in advanced disease. Glucopyranosyl lipid-A, a toll-like receptor 4 agonist that can ultimately mediate the adaptive immune response and increase pro-inflammatory signaling in the tumor microenvironment, has also demonstrated acceptable safety and clinical activity in Merkel cell carcinoma. Additional treatments under investigation for Merkel cell carcinoma include LAG3 and TIM3 inhibitors.

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The review article is limited by its lack of a pooled meta-analysis of the available data on immunotherapies and emerging therapies for Merkel cell carcinoma, which could have provided more conclusive remarks about these treatment options in these patients.


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Because checkpoint inhibition produces results in only half of patients with advanced Merkel cell carcinoma, the authors of this paper noted, additional research is needed to find “good predictive markers that could be helpful in better assessing the response to PD-1/PD-L1 inhibitors.” They also suggested that the use of checkpoint inhibitors as adjuvant and neoadjuvant therapy may be an interesting treatment approach.

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Reference

Kwiatkowska D, Reich A. Landscape of current and future therapies of Merkel cell carcinoma [published online February 21, 2020]. Dermatol Ther. doi: 10.1111/dth.13281