Immunotherapy in head and neck cancer: aiming at EXTREME precision

SZTURZ, Petr and J.B. VERMORKEN. Immunotherapy in head and neck cancer: aiming at EXTREME precision. BMC MEDICINE. LONDON: BIOMED CENTRAL LTD, 2017, vol. 15, No 110, p. 1-11. ISSN 1741-7015. Available from: https://dx.doi.org/10.1186/s12916-017-0879-4.

Basic information

• Original name: Immunotherapy in head and neck cancer: aiming at EXTREME precision
• Authors: SZTURZ, Petr (203 Czech Republic, guarantor, belonging to the institution) and J.B. VERMORKEN (56 Belgium).
• Edition: BMC MEDICINE, LONDON, BIOMED CENTRAL LTD, 2017, 1741-7015.

Other information

• Original language: English
• Type of outcome: Article in a journal
• Field of Study: 30218 General and internal medicine
• Country of publisher: United Kingdom of Great Britain and Northern Ireland
• Confidentiality degree: is not subject to a state or trade secret
• Impact factor: Impact factor: 9.088
• RIV identification code: RIV/00216224:14110/17:00099900
• Organization unit: Faculty of Medicine
• Doi: http://dx.doi.org/10.1186/s12916-017-0879-4
• UT WoS: 000402715100002
• Keywords in English: Head and neck cancer; Recurrent; Metastatic; Targeted therapy; Immunotherapy; Cetuximab; Nivolumab; Pembrolizumab; Biomarkers; Combination regimen
• Tags: EL OK
• Tags: International impact, Reviewed

Abstract

Background: Locoregionally advanced, recurrent, and metastatic squamous cell carcinomas of the head and neck (SCCHN) remain difficult to treat disease entities, in which systemic treatment often forms an integral part of their management. Immunotherapy is based on functional restoration of the host immune system, helping to counteract various tumour evasion strategies. Broadly, immunotherapeutic approaches encompass tumour-specific antibodies, cancer vaccines, cytokines, adoptive T-cell transfer, and immune-modulating agents. Until 2015, the epidermal growth factor receptor inhibitor cetuximab, a tumour-specific antibody, represented the only Food and Drug Administration (FDA)-approved targeted therapy for SCCHN. Subsequently, in 2016, the results from two prospective trials employing the immune-modulating antibodies nivolumab and pembrolizumab heralded a new era of anticancer treatment. Discussion: Nivolumab and pembrolizumab are monoclonal antibodies against programmed cell death protein-1 (PD-1), an 'immune checkpoint' receptor. Found on the surface of T-cells, PD-1 negatively regulates their activation and can thus be exploited during carcinogenesis. The second-line phase III trial CheckMate-141 randomly assigned 361 patients with recurrent and/or metastatic SCCHN in a 2: 1 ratio to receive either single-agent nivolumab (3 mg/kg intravenously every 2 weeks) or standard monotherapy (methotrexate, docetaxel, or cetuximab). Nivolumab improved the objective response rate (13% versus 6%) and median overall survival (OS; 7.5 versus 5.1 months, p = 0.01) without increasing toxicity. Exploratory biomarker analyses indicated that patients treated with nivolumab had longer OS than those given standard therapy, regardless of tumour PD-1 ligand (PD-L1) expression or p16 status. In the non-randomised, multicohort phase Ib study KEYNOTE-012, treatment with pembrolizumab achieved comparable results. Importantly, most of the responding patients had a long-lasting response. Conclusion: Based on recent results, nivolumab and pembrolizumab have been approved by the FDA as new standard-of-care options for the second-line treatment of recurrent and/or metastatic SCCHN. Generally well tolerated, these novel drugs demonstrated modest response rates, with tumour regressions usually being durable, even in platinum-resistant/refractory cases. The next step will be to extend the observed benefit to first-line treatment, currently dominated by the EXTREME regimen (platinum/5-fluorouracil/cetuximab), and to the locoregionally advanced setting, where concurrent chemoradiation with cisplatin is standard. Regimens combining immunotherapy with other modalities will probably further improve outcomes.