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Review
. 2020 Sep 21;12(9):2691.
doi: 10.3390/cancers12092691.

Immunotherapy Breakthroughs in the Treatment of Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

Christian Borel  1 , Alain C Jung  2   3 , Mickaël Burgy  1
Affiliations
Review

Immunotherapy Breakthroughs in the Treatment of Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

Christian Borel et al. Cancers (Basel). .

Abstract

Head and neck squamous cell carcinoma (HNSCC) in the recurrent or metastatic (R/M) setting is a devastating disease with a poor prognosis. Until recently, the reference first line treatment was the EXTREME protocol, which yields a 10.1 months median survival, and almost no effective treatment are available in second line. Immune checkpoint inhibitors (ICIs) have changed the prognosis of several metastatic solid tumors. Given their inflammatory profile and high mutational burden, HNSCC is a good candidate for ICIs treatments. First, a strong pembrolizumab efficacy signal was shown in the Keynote-012 Phase Ib study. Then, the phase III Checkmate-141 study validated the efficacy of nivolumab in platinum-resistant patients. Finally, the first line conquest is acquired since the final results of the keynote-048 phase III study that demonstrated the superiority of pembrolizumab versus EXTREME in CPS ≥ 1 patients, and with the addition of platinum and 5FU in all patients. However, the first line treatment landscape is not frozen. Two studies (Checkmate-651 and Kestrel) are investigating the efficacy of the combination of antibodies raised against CTLA-4 and PD-(L)1. Results are impatiently awaited. Further progress needs the use of new immunotherapeutic agents such as monalizumab or ICOS agonist rather in combination with an anti-PD(L)1. New associations of ICIs and chemotherapeutic or targeted therapeutic agents are also actively investigated. Finally, ICIs has to be studied in the locally advanced setting where there is a chance of cure. Several trials are testing the potential synergistic combination of ICIs with radiotherapy and platinum or cetuximab, or ICIs used in a neoadjuvant setting.

Keywords: cancer immunotherapy; head and neck squamous cell carcinoma; immune checkpoint inhibitors; recurrent or metastatic.

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Conflict of interest statement

C.B. is advisory board consultant for BMS and Astra Zeneca, and has received honoraria for consulting from Merck, BMS, Astra Zeneca and MSD. M.B. has received honoraria for consulting from BMS, Ipsen and MSD. A.J. declares no conflict of interest.

References

    1. Vermorken J.B., Mesia R., Rivera F., Remenar E., Kawecki A., Rottey S., Erfan J., Zabolotnyy D., Kienzer H.-R., Cupissol D., et al. Platinum-Based Chemotherapy plus Cetuximab in Head and Neck Cancer. N. Engl. J. Med. 2008;359:1116–1127. doi: 10.1056/NEJMoa0802656. - DOI - PubMed
    1. Machiels J.-P.H., Haddad R.I., Fayette J., Licitra L.F., Tahara M., Vermorken J.B., Clement P.M., Gauler T., Cupissol D., Grau J.J., et al. Afatinib versus methotrexate as second-line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck progressing on or after platinum-based therapy (LUX-Head & Neck 1): An open-label, randomised phase 3 trial. Lancet Oncol. 2015;16:583–594. - PubMed
    1. Vermorken J.B., Trigo J., Hitt R., Koralewski P., Diaz-Rubio E., Rolland F., Knecht R., Amellal N., Schueler A., Baselga J. Open-label, uncontrolled, multicenter phase II study to evaluate the efficacy and toxicity of cetuximab as a single agent in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck who failed to respond to platinum-based therapy. J. Clin. Oncol. 2007;25:2171–2177. - PubMed
    1. Saloura V., Cohen E.E.W., Licitra L., Billan S., Dinis J., Lisby S., Gauler T.C. An open-label single-arm, phase II trial of zalutumumab, a human monoclonal anti-EGFR antibody, in patients with platinum-refractory squamous cell carcinoma of the head and neck. Cancer Chemother. Pharmacol. 2014;73:1227–1239. doi: 10.1007/s00280-014-2459-z. - DOI - PubMed
    1. Ferris R.L. Immunology and Immunotherapy of Head and Neck Cancer. J Clin Oncol. 2015;33:3293–3304. doi: 10.1200/JCO.2015.61.1509. - DOI - PMC - PubMed