2018-19 Section 7-Neoplastic and Inflammatory Diseases of the Head and Neck eBook

Reprinted by permission of Curr Opin Otolaryngol Head Neck Surg. 2018; 26(2):152-156.

C URRENT O PINION

Immunotherapy for recurrent/metastatic head and neck cancer

Salvatore Alfieri a , Stefano Cavalieri a , and Lisa Licitra a,b

Purpose of review In the last decade, after cetuximab (anti-epidermal growth factor receptor), none of the novel investigated compounds has demonstrated benefit in head and neck squamous cell cancers (HNSCC), both in advanced and curative settings. Therefore, prognosis of recurrent/metastatic (R/M) HNSCC patients remains dismal, especially in platinum-refractory cohort. In the last few years, a new important class of drugs has affirmed its role. HNSCC, even if less ‘immunogenic’ than other malignancies (e.g. melanoma), was field of application of several new immune agents. To date, the most important data regard drugs acting on PD-1 (programmed death-1)/PD-L1 (programmed death-ligand 1) axis that is a crucial checkpoint used by tumor for immune escape. Our purpose is to summarize the results of these PD-1/PD-L1 inhibitors, outlining some critical points and few practical suggestions. Recent findings Nivolumab was recently approved by main regulatory agencies as second-line treatment for platinum- refractory R/M HNSCC. In the same setting, pembrolizumab was approved by FDA. Atezolizumab and durvalumab have already showed similar benefit in phase Ia and II studies, respectively. Summary Anti-PD1/PD-L1 agents are new effective therapies in R/M HNSCC. Their combination with conventional/ novel compounds, as well as a better selection of responding patients, could lead to improve current results. Keywords anti-programmed death-1/programmed death-ligand 1, head and neck cancer, immunotherapy, nivolumab, pembrolizumab

INTRODUCTION In the last decade, despite several new drugs have been investigated [1], the therapeutic armamentar- ium of head and neck squamous cell cancer (HNSCC) has never been enriched since the intro- duction of cetuximab, an antiepidermal growth factor receptor (EGFR) agent [2]. To date, prognosis for HNSCC patients is very dismal. One half of patients with locally advanced disease (Stage III– IV), primarily treated with curative intent, relapses and is no more curable [3–5]. In recurrent/meta- static (R/M) setting, life expectancy is shorter than 1 year (10 months) when the best first-line therapy available is feasible [1]. Moreover, less than half of R/M HNSCC (45%) is able to receive a second-line systemic treatment [6]. In this scenario, discovery of new therapies is eagerly awaited. Starting from this important clinical unmet need, immunotherapy, the newest finding in medical oncology, has been promptly applied within several clinical trials of

HNSCC. To be honest, however, the first sign of immune systemmodulation in HNSCC was already showed more than 20 years ago, when an Italian surgical group demonstrated, in a successful phase III study, a temporary tumor regression in R/M HNSCC treated with intratumoral injections of low dose of recombinant interleukin-2 [7]. In this review, we will summarize all the most important results and perspectives of the novel immune agents in R/MHNSCC, who are mainly directed against the PD-1 (programmed death-1)/PD-L1 (programmed a Department of Head and Neck Cancer Medical Oncology 3, Fondazione IRCCS Istituto Nazionale dei Tumori and b University of Milan, Milan, Italy Correspondence to Salvatore Alfieri, MD, Department of Head and Neck Cancer Medical Oncology 3, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Giacomo Venezian 1, zip code 20133, Milan, Italy. Tel: +39 02 2390 2765; e-mail: salvatore.alfieri@istitutotumori.mi.it Curr Opin Otolaryngol Head Neck Surg 2018, 26:152–156 DOI:10.1097/MOO.0000000000000448

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