Merkel Cell Carcinoma: Therapeutic Update and Emerging Therapies

Abstract

Merkel cell carcinoma (MCC) is a rare but highly aggressive neuroendocrine skin cancer whose incidence has almost doubled in recent decades. Risk factors for MCC include age > 65 years, immunosuppression, sun exposure and infection by Merkel cell polyomavirus. MCC usually presents as rapidly growing, firm, red to violaceous nodule localized on the sun-exposed skin. Surgery followed by radiation therapy is considered to be the first-line treatment for primary or loco-regional MCC in order to prevent recurrences and lymph node metastasis, while chemotherapy has always been used to treat advanced forms. However, responses to chemotherapy are mostly of short duration, and the associated clinical benefit on overall survival is still unclear. The use of checkpoint inhibitors (CPIs) has shown good results in the treatment of advanced MCC and, consequently, CPIs are considered emerging immunotherapeutic options for these patients, although there are still no standardized treatments for patients with metastatic disease. Here we present a complete overview of the different possibilities for the treatment of MCC according to the stage of the disease, focusing on the emerging immunotherapies used for treating advanced MCC.

Role and Therapeutic Targeting of the PI3K/Akt/mTOR Signaling Pathway in Skin Cancer: A Review of Current Status and Future Trends on Natural and Synthetic Agents Therapy

“…For instance, MLN0128, a compound that inhibits both mTORC1 and mTORC2, was able to potently suppress the growth of MCC both in vitro culture and in vivo in mouse xenograft models. MLN0128 is now at the verge of a dose escalation protocol in phase I clinical trial and undergoing a phase II clinical trial for the treatment of MCC [98,99].…”

A Therapeutic and Diagnostic Multidisciplinary Pathway for Merkel Cell Carcinoma Patients

“…Pembrolizumab, Avelumab, and Nivolumab have been studied both in patients pre-treated with chemotherapy and in patients who had not received previous chemotherapy. The percentage of objective tumor responses was 56-73% in the first line and 33-50% in the second, PFS was 17 months in the first line and 3 months in the second, OS not achieved in the first and 13 months in the second (34)(35)(36). PFS in the first-line pembrolizumab study was 17 months, with two thirds of patients alive at 2 years, far superior to historical chemotherapy results (34).…”

“…The percentage of objective tumor responses was 56-73% in the first line and 33-50% in the second, PFS was 17 months in the first line and 3 months in the second, OS not achieved in the first and 13 months in the second (34)(35)(36). PFS in the first-line pembrolizumab study was 17 months, with two thirds of patients alive at 2 years, far superior to historical chemotherapy results (34). In the study published with Avelumab in patients pre-treated with chemotherapy, although the percentage of objective responses and the PFS were almost comparable to those known for chemotherapy, in more than two thirds of the responsive patients the response lasted at least a year, done completely new and much more favorable than what is known for chemotherapy, which must be added to a 13-month OS with Avelumab compared to almost six for chemotherapy.…”

Mild Hypofractionated Radiation Therapy for Merkel Cell Carcinoma

“…Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine neoplasm [1,2]. Surgery (i.e., wide excision) is the standard treatment for primary MCCs [1].…”