The majority of patients diagnosed with recurrent and/or metastatic squamous cell carcinoma of the head and neck are deemed ineligible for surgery or irradiation. Their management prioritise symptom control and quality-of-life improvement. According to patient’s performance status, medical comorbidities and symptoms, recommended treatment options include supportive care only, mono- or multi-drug chemotherapy or cetuximab (epidermal growth factor receptor inhibitor) either alone or as an adjunct to cytotoxic drugs. Despite achieving response rates superior to single-agents, doublet and triplet regimens incorporating cisplatin and/or taxanes did not increase overall survival and were often difficult to tolerate. The
platinum (cisplatin or carboplatin)/5-fluorouracil/cetuximab regimen is the only regimen showing significant survival improvement over PF alone in a large randomised trial, and therefore is the only approved new standard systemic treatment today. However, the very poor overall survival of six to ten months expected in this patient population, remains a continuous challenge and novel anticancer therapies are urgently needed. The potential to induce durable responses with manageable toxicity has propelled immunotherapy to the forefront of cancer research, yet its validation in phase III clinical trials is pending. Another crucial task is the identification of reliable, prospectively confirmed prognostic and predictive
biomarkers. Mounting evidence from retrospective analyses suggests that human papillomavirus status with p16 immunohistochemical positivity as its surrogate represent promising candidates for this role.