Immunotherapy in head and neck cancer: aiming at EXTREME
precision

J 2017

Immunotherapy in head and neck cancer: aiming at EXTREME precision

SZTURZ, Petr and J.B. VERMORKEN

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

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30218 General and internal medicine

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

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

Abstract

V originále

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.

Citovat

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.

@article{1406901,
   author = {Szturz, Petr and Vermorken, J.B.},
   article_location = {LONDON},
   article_number = {110},
   doi = {http://dx.doi.org/10.1186/s12916-017-0879-4},
   keywords = {Head and neck cancer; Recurrent; Metastatic; Targeted therapy; Immunotherapy; Cetuximab; Nivolumab; Pembrolizumab; Biomarkers; Combination regimen},
   language = {eng},
   issn = {1741-7015},
   journal = {BMC MEDICINE},
   title = {Immunotherapy in head and neck cancer: aiming at EXTREME precision},
   volume = {15},
   year = {2017}
}

TY  - JOUR
ID  - 1406901
AU  - Szturz, Petr - Vermorken, J.B.
PY  - 2017
TI  - Immunotherapy in head and neck cancer: aiming at EXTREME precision
JF  - BMC MEDICINE
VL  - 15
IS  - 110
SP  - 1-11
EP  - 1-11
PB  - BIOMED CENTRAL LTD
SN  - 17417015
KW  - Head and neck cancer
KW  - Recurrent
KW  - Metastatic
KW  - Targeted therapy
KW  - Immunotherapy
KW  - Cetuximab
KW  - Nivolumab
KW  - Pembrolizumab
KW  - Biomarkers
KW  - Combination regimen
N2  - 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.
ER  -

SZTURZ, Petr and J.B. VERMORKEN. Immunotherapy in head and neck cancer: aiming at EXTREME precision. \textit{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.

Detailed Information on Publication Record