Advanced Non-Melanoma Skin Cancer: Systemic Treatment Update
Posted: Tuesday, October 22, 2019
Keiji Tanese, MD, PhD, of the Keio University School of Medicine in Tokyo, and colleagues reviewed the systemic treatment options available for advanced types of non-melanoma skin cancers in Frontiers in Medicine. “Advances in our molecular biological understanding of [non-melanoma skin cancers] and improvement of drug discovery techniques over the past several decades have facilitated the establishment of novel treatment strategies,” stated the authors.
The most common type of skin cancer, basal cell carcinoma, is usually slow-growing and has a low metastatic potential, although deeply invasive or large lesions can sometimes metastasize. Two targeted therapies, vismodegib and sonidegib, are currently available for advanced basal cell carcinoma. They both work by blocking Hedgehog signaling activation. The antifungal drug itraconazole has been reported to decrease tumor size as well.
For the treatment of advanced squamous cell carcinoma, commonly used chemotherapeutic agents include bleomycin, platinum, anthracycline, taxanes, interferon alpha, fluorouracil, and capecitabine. Because of the frequent overexpression of or mutations in EGFR in squamous cell carcinoma, agents that target EGFR have also been evaluated. Although the monoclonal antibodies cetuximab and panitumumab appear to be effective, especially in combination with chemotherapy, oral small molecules such as gefitinib and erlotinib have shown limited efficacy.
Additionally, the anti–PD-1 monoclonal antibody cemiplimab was approved in 2018 to treat advanced squamous cell carcinoma after demonstrating “impressive” efficacy.
Extramammary Paget’s disease is a rare intraepithelial adenocarcinoma; it typically grows slowly and is associated with a favorable prognosis with surgical resection. However, once extramammary Paget’s disease invades the dermis, it can easily metastasize, and the prognosis becomes poor. Treatment options include several cytotoxic chemotherapy regimens and trastuzumab for patients with HER2-positive disease.
The highly aggressive cutaneous neuroendocrine Merkel cell carcinoma is also rare. Several chemotherapeutic regimens, including platinum plus etoposide and cyclophosphamide plus doxorubicin plus vincristine, have been preferred options for advanced disease. Unfortunately, the response of Merkel cell carcinoma to chemotherapy is rarely durable, and resistance develops quickly. More recently, the monoclonal PD-L1 antibodies avelumab and pembrolizumab were approved for advanced Merkel cell carcinoma after studies in chemotherapy-refractory and treatment-naive patients, respectively.
Disclosure: The study authors reported no conflicts of interest.