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Head and Neck Cancer Editorial Head and Neck Cancer Highlights of ESMO Congress 2014 Panagiota Economopoulou, 1 Giannis Kotsantis, 1 George Kavourakis 1 and Amanda Psyrri 2 1. Medical Oncology Fellow; 2. Assistant Professor, Division of Oncology, Second Department of Internal Medicine, Attikon University Hospital, Chaidari, Athens, Greece Abstract Head and neck squamous cell carcinoma (HNSCC) is a challenging cancer to treat and cure. A great proportion of patients present with advanced disease and appropriate treatment options include surgical resection with adjuvant radiotherapy (RT) or chemoradiotherapy (CRT), radical concurrent CRT or RT with monoclonal antibody cetuximab. Despite improved outcomes with CRT, overall prognosis is still unsatisfactory and treatment-related toxicity is a matter of major importance. To obtain improved outcomes and mitigate disease recurrence, current research is focused on novel molecular targeted agents, immunotherapy and discovery of predictive markers. Herein, we summarise recent advances in treatment of head and neck cancer, as presented in European Society for Medical Oncology (ESMO) Congress 2014. Keywords Head and neck cancer, afatinib, immunotherapy, ESMO highlights Disclosures: Panagiota Economopoulou, Giannis Kotsantis, George Kavourakis and Amanda Psyrri have no conflicts of interest to declare. No funding was received in the publication of this article. Received: 5 December 2014 Accepted: 9 December 2014 Citation: European Oncology & Haematology, 2014;10(2):96–7 Correspondence: Amanda Psyrri, 1st Rimini St, 12462, Haidari, Athens, Greece E: firstname.lastname@example.org Despite advances in multimodality treatment, the 5-year survival rate of patients with locally advanced head and neck squamous cell carcinoma (HNSCC) does not exceed 40–50% and survival rates for recurrent or metastatic disease (R/M) remain dismal. 1,2 Low survival rates in combination with significant toxicities caused by current treatment strategies used in HNSCC emphasise the necessity for new treatment options. For patients with recurrent or metastatic disease, recommended treatment is cisplatin-based chemotherapy ± cetuximab for fit patients and single agent chemotherapy (methotrexate) or cetuximab for patients with poor performance status (PS), albeit with limited efficacy. 3 In this setting, strategies to improve outcome include the introduction of novel therapeutic strategies and molecular targets, as well as intensification of treatment. The epidermal growth factor receptor (EGFR), a transmembrane tyrosine kinase receptor belonging to the HER/ErbB family, is a long-standing challenging target in HNSCC, as it is overexpressed in up to 90 % of cases; 4 overexpression of EGFR also correlates with poor clinical outcomes. 5 Cetuximab, a chimeric immunoglobulin G1– human monoclonal antibody against the extracellular domain of EGFR, has emerged as a powerful tool in the treatment of R/M head and neck cancer. In the Erbitux in First Line Treatment of Recurrent or Metastatic Head and Neck Cancer (EXTREME) study, the addition of cetixumab to platinum-based chemotherapy with fluorouracil was shown to improve overall survival (OS), progression-free survival (PFS) and response rates. 6 However, cetuximab has demonstrated modest response rates when used as monotherapy. 7 Afatinib, an oral irreversible ErbB family blocker that inhibits all kinase-active members (EGFR, HER2 and HER4), which is currently approved for the treatment of EGFR mutated non-small-cell lung cancer, 8 has been shown similar antitumour effects compared with cetuximab in R/M HNSCC in a phase II trial. 9 96 Based on these results, the phase III LUX-Head and Neck 1 clinical trial presented at the European Society for Medical Oncology (ESMO) Congress 2014 assessed the efficacy of afatinib as monotherapy compared with single agent methotrexate as second-line treatment in HNSCC. 10 Patients were stratified according to PS and prior use of cetuximab. The study met its primary endpoint showing an increase in PFS of 0.9 months with afatinib compared with methotrexate (2.6 versus 1.7 months, hazard ratio (HR) 0.8; p=0.03). In addition, it showed improvement in tumour shrinkage and response rate in favour of afatinib. 10 The difference in PFS of 0.9 months is of unclear significance and unlikely to lead to drug approval. However, this study is important, as it is the second study since the EXTREME trial that showed benefit of a novel agent in HNSCC and the first study to demonstrate an active oral targeted agent in HNSCC. Of note, subgroup analysis showed a benefit primary seen in EGFR-naïve patients, suggesting a degree of cross-resistance that was not seen in phase II studies. 9 Ongoing studies evaluating adjuvant afatinib in locally advanced HNSCC after chemoradiotherapy (LUX-Head and Neck-2) will hopefully clarify the effectiveness of afatinib; 11 until then, active search of predictive biomarkers might lead to identification of specific groups of patients with greater benefit. Another rationale for improvement of treatment strategies in HNSCC is to overcome resistance to cetuximab, which might lead to tumour progression after initial clinical response. One proposed mechanism of de novo or acquired resistance in HNSCC is HER3 activation. 12 MEHD7945A is a monoclonal antibody that simultaneously blocks ligand binding to EGFR and HER3 and inhibits signalling by all major ligand- dependent HER family members. 13 It has shown superior preclinical activity compared with mono-specific HER antibodies, particularly in HNSCC and has displayed activity in cetuximab-resistant models. 13 © Touc h ME d ic al ME d ia 2014