Review
Cetuximab in the management of locoregionally advanced head and neck cancer: Expanding the treatment options?

https://doi.org/10.1016/j.ejca.2010.05.015Get rights and content

Abstract

The treatment of locoregionally advanced squamous cell carcinoma of the head and neck (SCCHN) has evolved in recent years as a consequence of a better understanding of the potential benefits associated with altered radiation fractionation regimens, concurrently administered chemotherapy and radiotherapy (chemoradiotherapy) and induction chemotherapy. Concurrent chemoradiotherapy is a treatment option for technically resectable disease, where functional morbidity precludes the use of surgery. Induction chemotherapy followed by radiotherapy may also be used in this setting, and has been validated for larynx preservation. Concurrent chemoradiotherapy is a standard treatment approach for medically fit patients with locoregionally advanced unresectable disease. However, the toxicity burden of additional chemotherapy in both the concurrent chemoradiotherapy and induction chemotherapy settings can have implications for treatment compliance and may impede the administration of chemotherapy and/or radiotherapy to schedule. The epidermal growth factor receptor (EGFR)-targeted IgG1 monoclonal antibody, cetuximab (Erbitux®), has shown significant clinical benefits in the treatment of both locoregionally advanced and recurrent and/or metastatic SCCHN. A phase III study in locoregionally advanced disease demonstrated significant improvements in locoregional control and progression-free and overall survival with cetuximab plus radiotherapy compared with radiotherapy alone, and overall survival benefits were maintained at 5 years. The addition of cetuximab to concurrent chemoradiotherapy has been shown to be feasible in phase II trials and is being investigated in phase III trials. Preliminary evidence suggests that cetuximab could be incorporated into induction management strategies. Taken together, these data support an important role for cetuximab in the treatment paradigm for locoregionally advanced SCCHN.

Introduction

Head and neck carcinomas encompass a number of different tumour types affecting various anatomical sites. Cancers of the oral cavity, larynx and pharynx together account for around 5% of global cancer incidence.1 Squamous cell carcinomas of the head and neck (SCCHN) are associated with a relatively high risk of developing second primary malignancies. The survival of patients with SCCHN is related to disease stage, performance status and comorbidities.2, 3, 4

In this review we discuss the role of the epidermal growth factor receptor (EGFR)-targeting IgG1 monoclonal antibody (MAb) cetuximab in current and future treatment strategies for locoregionally advanced SCCHN.

Section snippets

Radiotherapy and concurrent chemoradiotherapy

Locoregionally advanced SCCHN is generally treated with curative intent and aggressive treatment approaches are commonly used. Where disease is resectable, surgery followed by conventionally fractionated radiotherapy is a standard treatment option.5 However, patients at a high risk of relapse may benefit from the post-operative administration of radiotherapy and concurrent chemotherapy (chemoradiotherapy) and this is now considered a standard of care in this setting.5 Concurrent

Induction chemotherapy

The use of a sequential approach, whereby chemotherapy (induction chemotherapy) is administered prior to radiotherapy or concurrent chemoradiotherapy, is being evaluated as an alternative option for patients with locoregionally advanced, unresectable disease. This approach has already been validated in the setting of larynx preservation in patients with resectable disease, when induction chemotherapy is followed by radiation therapy in good responders.38 Data from a subset analysis of patients

Safety and tolerability of cetuximab

The most common adverse events observed with cetuximab are skin reactions, which may develop in more than 80% (any grade) of patients. Acne-like rash is the most frequently observed skin reaction. There is an indication from some studies in SCCHN that the severity of rash is associated with efficacy.18, 57, 58 In the Bonner trial, in patients receiving cetuximab, the risk of death was significantly lower in patients developing grade 2 or higher rash than in those with grade 1 rash or no rash

Conclusions

The role of cetuximab in the treatment of locoregionally advanced head and neck cancer continues to develop. The data from a phase III trial support the role of cetuximab plus radiotherapy as an effective treatment option for patients with locoregionally advanced SCCHN. Adding cetuximab to radiotherapy led to significant improvements in locoregional control and survival and these survival improvements were maintained long-term, with a nine percentage point advantage for cetuximab plus

Conflict of interest statement

J. Bourhis reports receiving advisory board honoraria from GlaxoSmithKline, Merck KGaA and sanofi-aventis. J.-L. Lefebvre reports receiving lecture and advisory board honoraria from Merck KGaA and sanofi-aventis. J.B. Vermorken reports receiving lecture and advisory board honoraria from Amgen, Boehringer Ingelheim, Lilly, Merck KGaA and sanofi-aventis.

Acknowledgement

Editorial support for the production of this manuscript was funded by Merck KGaA.

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