Immunotherapeutic strategies in patients with advanced head and neck squamous cell carcinoma

Abstract

Most head and neck squamous cell carcinoma (HNSCC) patients present with advanced-stage disease often with significant rates of local failure and distant metastases (1). Over the past two decades, the survival rates of HNSCC patients have not been altered significantly by standard therapy (2). Immune dysfunction has been demonstrated in patients with HNSCC and this was correlated with either a defect of their antitumor immune responses and/or tumor progression and relapse (3). Immunotherapy has emerged as a promising treatment approach to improve such immune dysfunction. Interventions at immune checkpoints like CTLA-4, PD-1 and others are aimed at reconstituting immunosurveillance or T-cell mediated elimination of malignant cells. The effector and regulatory T cell compartments are targeted to resurrect an efficient T cells function. The assumption is that specific antigens are targeted and much debate is ongoing on what the most important target antigens may be mutated neo-antigens or constitutive cellular antigens like the cancer testis family of antigens (CTA) which are expressed preferentially in cancer cells like the MAGE family of antigens, NY-ESO-1 and others (4). The PD-1 pathway, an important immune checkpoint, has been demonstrated to be an effective target in HNSCC (5-8). Pembrolizumab is an anti-PD-1 antibody that was approved for patients with HNSCC (recurrent or metastatic) with disease progression on or after platinum-containing chemotherapy (9). The efficacy and safety outcomes from a phase Ib multi-cohort KEYNOTE-012 trial (ClinicalTrials.gov, NCT01848834) were the basis of approval of pembrolizumab in advanced solid tumors. In this trial study, Tahara et al. (9) recently reported their results from a subset of 26 patients with recurrent/metastatic HNSCC from the Asia-Pacific region. In these patients, durable anti-tumor response was observed with limited side effects. Five patients achieved a confirmed partial response (PR) with an overall response rate (ORR) of 19%; another 8 (31%) patients achieved stable disease (SD); and 12 (46%) patients had progressive disease (PD). No patients achieved a complete response. It is important to mention here that most of these patients (73%) had a history of smoking which is a main cause of somatic mutations in cancer (10) since cigarette smoke has over 60 carcinogens (11). In addition, 92% of the patients received prior platinum treatment such as cisplatin an alkylating agent also known to be a mutagenic compound (12).