Head and neck cancer and immunotherapy: current knowledge and perspective

Abstract

As with many types of cancer, immunotherapy is changing the management of squamous cell carcinoma of the head and neck (HNSCC). In a locally advanced or metastatic setting, treatment options have long been curtailed, but this paradigm is currently changing. Checkpoint inhibitors were the first to be validated in second-line treatment with PD-1 and PD-L1 inhibitors and these treatments are available in USA for first-line use. In addition, many studies are underway to use its molecules earlier in the care or try to increase their effectiveness with associations. The issues of patient selection that would benefit the most from immunotherapy and the evaluation of the response to these treatments are not completely solved. The goal is here to update the possibilities of current treatment by immunotherapy in HNSCC as well as on various development pathways in progress.

Keywords

Head and neck squamous cell carcinoma / checkpoint inhibitors / immunotherapy / clinical trial

References

[1] Bray F,Soerjomataram I,Torre LA.Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries..CA Cancer J Clin2018;68:394-424

[2] Karabajakian A,Neidhardt EM,Saintigny P.Chemotherapy for recurrent/metastatic head and neck cancers..Anticancer Drugs2017;28:357-61

[3] Ferris RL,Fayette J,Colevas AD.Nivolumab vs investigator’s choice in recurrent or metastatic squamous cell carcinoma of the head and neck: 2-year long-term survival update of CheckMate 141 with analyses by tumor PD-L1 expression..Oral Oncol2018;81:45-51 PMCID:PMC6563923

[4] Cohen EEW,Le Tourneau C,Licitra L.Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised, open-label, phase 3 study..Lancet2019;393:156-67

[5] Ferris RL,Haddad R,Goswami T.Phase III, randomized, open-label study of durvalumab (MEDI4736) monotherapy, or durvalumab + tremelimumab, versus standard of care (SoC), in recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN): eagle..J Immunother Cancer2015;3:P150 PMCID:PMC4645286

[6] Burtness B, Harrington KJ, Greil R, Soulières D, Tahara M, et al. KEYNOTE-048: Phase 3 study of first-line pembrolizumab (P) for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). Available from: https://oncologypro.esmo.org/Meeting-Resources/ESMO-2018-Congress/KEYNOTE-048-Phase-3-study-of-first-line-pembrolizumab-P-for-recurrent-metastatic-head-and-neck-squamous-cell-carcinoma-R-M-HNSCC. [Accessed on 23 Oct 2019]

[7] Sun XS,Tao Y,Alfonsi M.A phase II randomized trial of pembrolizumab versus cetuximab, concomitant with radiotherapy (RT) in locally advanced (LA) squamous cell carcinoma of the head and neck (SCCHN): first results of the GORTEC 2015-01 “PembroRad” trial..J Clin Oncol2018;36:6018

[8] Uppaluri R,Lin T,Jackson RS.Neoadjuvant pembrolizumab in surgically resectable, locally advanced HPV negative head and neck squamous cell carcinoma (HNSCC)..J Clin Oncol2017;35:6012

[9] Ferris RL,Baxi SS,Gauthier H.LBA46An open-label, multicohort, phase 1/2 study in patients with virus-associated cancers (CheckMate 358): safety and efficacy of neoadjuvant nivolumab in squamous cell carcinoma of the head and neck (SCCHN)..Ann Oncol2017;28:

[10] Economopoulou P,Psyrri A.The promise of immunotherapy in head and neck squamous cell carcinoma: combinatorial immunotherapy approaches..ESMO Open2016;1:e000122 PMCID:PMC5548974

[11] Cho BC,Ravaud A,Isambert N.1048OM7824 (MSB0011359C), a bifunctional fusion protein targeting PD-L1 and TGF-β, in patients (pts) with advanced SCCHN: results from a phase I cohort..Ann Oncol2018;29:

[12] André P,Soulas C,Lopez J.Anti-NKG2A mAb is a Checkpoint Inhibitor that Promotes Anti-tumor Immunity by Unleashing Both T and NK Cells..Cell2018;175:1731-43.e13 PMCID:PMC6292840

[13] Cohen EEW,Hong DS,Brana I.1044OA phase Ib/II study (SCORES) of durvalumab (D) plus danvatirsen (DAN; AZD9150) or AZD5069 (CX2i) in advanced solid malignancies and recurrent/metastatic head and neck squamous cell carcinoma (RM-HNSCC): Updated results..Ann Oncol2018;29:mdy287

[14] Cohen EEW,Wong DJL,Daniels GA.Phase 1b/2, open label, multicenter study of intratumoral SD-101 in combination with pembrolizumab in anti-PD-1 treatment naïve patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC)..J Clin Oncol2019;37:6039

[15] Mitchell TC,Smith DC,Wasser JS.Epacadostat plus Pembrolizumab in patients with advanced solid tumors: phase I results from a multicenter, open-label phase I/II trial (ECHO-202/KEYNOTE-037)..J Clin Oncol2018;JCO2018789602 PMCID:PMC6225502

[16] Taylor MH,Brose MS,Richey SL.A phase 1b/2 trial of lenvatinib plus pembrolizumab in patients with squamous cell carcinoma of the head and neck..J Clin Oncol2018;36:6016

[17] Bell RB,Leidner RS,Ballesteros-Merino C.Neoadjuvant anti-OX40 (MEDI6469) prior to surgery in head and neck squamous cell carcinoma..J Clin Oncol2018;36:6011

[18] Ogasawara M,Yamagishi Y.Phase I/II pilot study of Wilms’ tumor 1 peptide-pulsed dendritic cell vaccination combined with conventional chemotherapy in patients with head and neck cancer..Ther Apher Dial2019;23:279-88

[19] Haddad R,Blumenschein G,Guigay J.Nivolumab treatment beyond RECIST-defined progression in recurrent or metastatic squamous cell carcinoma of the head and neck in CheckMate 141: a subgroup analysis of a randomized phase 3 clinical trial..Cancer2019;125:3208-18 PMCID:PMC6771504

[20] Saâda-Bouzid E,Karabajakian A,Servois V.Hyperprogression during anti-PD-1/PD-L1 therapy in patients with recurrent and/or metastatic head and neck squamous cell carcinoma..Ann Oncol2017;28:1605-11

[21] Foster CC,Khattri A,Dekker A.Association of immune-related adverse events (irAEs) with improved response, progression-free survival, and overall survival for patients with metastatic head and neck cancer receiving anti-PD-1 therapy..J Clin Oncol2018;36:6014

[22] De Cecco L,Giannoccaro M,Bossi P.Head and neck cancer subtypes with biological and clinical relevance: meta-analysis of gene-expression data..Oncotarget2015;6:9627-42 PMCID:PMC4496244

[23] Hanna GJ,Jones RE,Lizotte PH.Defining an inflamed tumor immunophenotype in recurrent, metastatic squamous cell carcinoma of the head and neck..Oral Oncol2017;67:61-9

[24] Khagi Y,Daniels GA,Sacco AG.Hypermutated circulating tumor DNA: correlation with response to checkpoint inhibitor-based immunotherapy..Clin Cancer Res2017;23:5729-36 PMCID:PMC5678984

[25] Kirtane K,Slebos R.Association between human papillomavirus (HPV) status and duration of response of anti-programmed cell death protein-1 (PD-1) inhibitors in patients with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC)..J Clin Oncol2019;37:6044

[26] Foster CC,Khattri A,Dekker A.Association of a baseline neutrophil-to-lymphocyte ratio (NLR) with progression-free and overall survival in head and neck cancer patients receiving anti-PD-1 therapy..J Clin Oncol2018;36:6038