Treatment approaches of advanced cutaneous squamous cell carcinoma

Abstract

Common primary cutaneous squamous cell carcinoma (CSCC) accounts for 20% of keratinocyte cancers that is usually successfully treated with surgery or radiotherapy. In a minority of cases, CSCC lesions may progress to locally advanced or metastatic disease that may be difficult to be treated causing significant morbidity and mortality. Chemotherapies and targeted therapy with anti‐epidermal growth factor receptor antibodies have been used off‐label in small studies and case reports of advanced CSCC, but data are scarce and response short‐lived. Recently, two PD‐1 immune checkpoint inhibitors, cemiplimab and pembrolizumab, have been approved for the treatment of advanced CSCC; specifically the former can be administered in patients with locally advanced and metastatic tumours, while the latter in case of recurrent metastatic CSCC. The introduction of immune checkpoint inhibitors represents a breakthrough in the treatment of CSCC, since numerous clinical trials showed that these agents may provide remarkable clinical benefit with an acceptable safety profile, in a high‐need population who had no standard of care. In addition, real‐world studies are needed to validate the results observed in clinical trials and numerous clinical trials in the neoadjuvant or adjuvant setting are ongoing. Finally, further studies should investigate predictive biomarkers useful to better select patients to maximize the treatment efficacy.

Retrospective, Registry-based, Cohort Investigation of Clinical Outcomes in Patients with Cutaneous Squamous Cell Carcinoma and Basal Cell Carcinoma in Finland

“…Survival of the patients with advanced cSCC that had been operated 3 times was the highest compared with those treated with radiotherapy or chemotherapy. Although the advanced cSCC patient population is heterogeneous, the result of the current study on survival of the patients reflects the need for new treatment options ( 28 ).…”

Recent Trends in the Integrated Management of Cutaneous Squamous Cell Carcinoma

“…In culmination, the anti-PD1 agents cemiplimab and pembrolizumab are approved by the FDA for the treatment of advanced cSCC. Presently, immune checkpoint inhibitors are the standard of care in locally advanced and metastatic cSCC [58][59][60][61].…”

“…Cetuximab can be used in combination with radiotherapy or chemotherapy [72]. Contemporary international clinical guidelines recommend cetuximab in cases that fail to respond to or have contraindications for immune checkpoint inhibitors [61]. EGFR has been identified as a key therapeutic target in various tumor types.…”

“…Polychemotherapy with cytotoxic agents such as carboplatin, 5-fluorouracil, methotrexate, bleomycin, and gemcitabine have been employed as off-label chemotherapy in advanced cSCC. Recent guidelines state that these systemic chemotherapies can be used only in cases that fail to respond or are intolerant to anti-PD-1 immunotherapy [61].…”

TEAD1 Silencing Regulates Cell Proliferation and Resistance to 5-Fluorouracil in Cutaneous Squamous Cell Carcinoma

“…Targeted therapy with anti-EGFR (epidermal growth factor receptor) antibodies and PD-1 immune checkpoint inhibitors have been used in advanced cSCC. 4 However, each of these methods has its own limitations. EGFR inhibitors have activity only in a subset of patients.…”