Authors: Alessia Villani, Luca Potestio, Gabriella Fabbrocini & Massimiliano Scalvenzi
Abstract
Non-melanoma skin cancers, also known as keratinocyte tumors, have an increasing incidence worldwide, with basal cell carcinoma and squamous cell carcinoma being the most represented ones. Although surgery represents the gold-standard treatment for both tumors, some cases can progress to an advanced or a metastatic state and targeted therapy is required. Hedgehog signaling pathway has an important role in the development of basal cell carcinoma, and its inhibition is the key to new treatment options available for the treatment of locally advanced and metastatic basal cell carcinoma. Cutaneous squamous cell carcinoma is the second most frequent malignant skin cancer; when presenting in advanced or metastatic stage, alternative treatments are required; cemiplimab is a human monoclonal antibody directed against programmed cell death-1 receptor that acts by blocking T-cell inactivation and is the first drug approved for the treatment of adult patients with metastatic or locally advanced cutaneous squamous cell carcinoma. Studies evaluating pembrolizumab, ipilimumab and nivolumab as alternative treatments for advanced squamous cell carcinoma are still underway. Objective of this review is to analyze and discuss the novel therapies for advanced basal cell carcinoma and squamous cell carcinoma to obtain a sharper perspective of the available treatment options.
Key Summary Points |
Why carry out this study?Surgical excision remains the main recommended therapy for easy-to-treat basal cell carcinoma (BCC), while difficult-to-treat BCC, including locally advanced BCC (laBCC) and metastatic BCC (mBCC), still represent the real challenge The majority of cutaneous squamous cell carcinoma (cSCC)s are successfully treated with surgical excision and radiation therapy. However, treating metastatic cSCC and locally advanced cSCC (lacSCC) remains the main goal of clinical practice New emerging treatment options for advanced forms of BCC and squamous cell carcinoma (SCC) are required to offer non-invasive alternatives to patients not eligible for conventional treatments |
What was learned from the study?Hedgehog inhibitors (HHIs) are promising alternative treatments for patients with advanced basal cell carcinomas; vismodegib and sonidegib, two oral smoothened (SMO) antagonists, have already been approved for the treatment of adult patients with advanced basal cell carcinoma Currently, US Food and Drug Administration (FDA) has granted Orphan Drug and Breakthrough Therapy Designation for topical patidegib gel formulation in patients with basal cell carcinoma nevus syndrome, also known as Gorlin syndrome Cemiplimab has been approved by the European Medicines Agency (EMA) and Food and Drug Administration (FDA) for the treatment of adult patients with metastatic or locally advanced cutaneous squamous cell carcinoma, not eligible for surgery or radiotherapy, and for adult patients with locally advanced or metastatic BCC intolerant to a HH pathway inhibitor |