In comparison with adenocarcinomas, squamous cell carcinomas (SCC) are more biologically aggressive and more difficult to treat with available systemic therapy. Combined chemotherapy remains the first-line treatment of patients with advanced SCC, novel therapeutic options are represented by monoclonal antibodies (ramucirumab, necitumumab) and particularly by immunotherapy with immune checkpoint inhibitors (nivolumab, pembrolizumab), which lead to sustained treatment response and are effective even in heavily pretreated patients.
Use of targeted therapy in patients with SCC is complicated owing to genetic heterogeneity, mutation burden and lack of driver mutation. In contrast, immunotherapy is supposed to play an important, if not even crucial role in SCC patients in the future.