Spotlight on Cetuximab in Squamous Cell Carcinoma of the Head and Neck†

Abstract

Cetuximab (Erbitux®) is a chimeric monoclonal antibody directed against the human epidermal growth factor receptor (EGFR). EGFR is overexpressed and/or upregulated in most squamous cell carcinomas of the head and neck (SCCHN); this overexpression is associated with more aggressive disease and poorer prognosis. In the EU, cetuximab is approved in combination with radiation therapy for the treatment of locally advanced SCCHN and in combination with platinum-based chemotherapy for the treatment of recurrent and/or metastatic SCCHN. In randomized, open-label, multinational, phase III clinical trials, cetuximab plus radiotherapy significantly improved the duration of locoregional control (primary endpoint) compared with radiotherapy alone in patients with locally advanced SCCHN, while cetuximab plus first-line platinum-based chemotherapy significantly improved overall survival (primary endpoint) compared with first-line platinum-based chemotherapy alone in patients with recurrent and/or metastatic SCCHN. The efficacy benefits of cetuximab-based combination therapy were achieved without an adverse impact on patients' health-related quality of life. In addition, cetuximab had an acceptable tolerability profile when added to radiotherapy or platinum-based chemotherapy; in particular, it did not exacerbate the toxicities commonly associated with these other treatment modalities. Cetuximab-related adverse events, which include skin rash, hypomagnesemia and infusion-related reactions, are mostly mild to moderate in severity and manageable. Thus, cetuximab-based combination therapy is a valuable treatment option in patients with SCCHN. In the setting of locally advanced, unresectable disease, cetuximab plus radiotherapy offers an alternative approach to the current standard of care, namely platinum-based chemotherapy plus radiotherapy (chemoradiotherapy). Based on informal comparisons, cetuximab plus radiotherapy appears to be at least as effective as chemoradiotherapy and, moreover, less toxic; however, formal comparisons of these regimens are required before their relative efficacy and tolerability can be conclusively determined. In the setting of recurrent and/or metastatic SCCHN, cetuximab plus platinum-based chemotherapy provides a first-line treatment of choice for fit patients in whom palliative chemotherapy is indicated.

Antiproliferative and proapoptotic activity of CLM3, a novel multiple tyrosine kinase inhibitor, alone and in combination with SN-38 on endothelial and cancer cells

“…Thus, the most targeted area of developing antineoplastic drugs is through the inhibition of EGFR and VEGFR signaling. This therapeutic strategy in oncology has been successful using biologics, cetuximab [26] and ramucirumab [27], as well as small molecules such as gefitinib [28], vandetanib [8], sorafenib, sunitinib [1]. As an example, the direct inhibition of VEGFR-2 tyrosine kinase activity with a small molecule (sorafenib and sunitinib) has been recently approved by the FDA for the treatment of renal cell cancer.…”

Management of cutaneous squamous cell carcinoma in patients with epidermolysis bullosa: best clinical practice guidelines

“…A raft of new biologic agents, notably epidermal growth factor receptor (EGFR) antagonists and tyrosine kinase inhibitors, have been used in non-EB SCCs. [80][81][82][83][84][85] There are limited case reports of favourable results with cetuximab (a monoclonal antibody that binds the extracellular domain of EGFR) in metastatic EB SCCs strongly expressing EGFR. 30,36 The oral tyrosine kinase inhibitor erlotinib may be another putatively use-ful agent for advanced disease in this patient group.…”

Cetuximab/cisplatin and radiotherapy in HNSCC: is there a favorite choice?

“…In randomized, open-label, multinational, phase III clinical trials, cetuximab plus radiotherapy significantly improved the duration of locoregional control compared with radiotherapy alone in patients with locally advanced HNSCC [6]; in addition, cetuximab had an acceptable tolerability profile when added to radiotherapy and it did not exacerbate the toxicities commonly associated with these other treatment modalities, without an adverse impact on patients' health-related quality of life [7]. Therefore, cetuximab plus radiotherapy offers an alternative approach to the current standard of care (platinum-based chemotherapy plus radiotherapy) in the setting of locally advanced, unresectable disease.…”