Window of opportunity trials in head and neck cancer

Abstract

Head and neck squamous cell carcinoma (HNSCC) has a large global burden of disease and poor survival outcomes. Recent targeted therapies and immunotherapies have been explored in HNSCC, but there has been limited translation to clinical practice outside of recurrent or metastatic cases. Window of opportunity settings, where novel agents are administered between cancer diagnosis and planned definitive therapy, have begun to be employed in HNSCC. Tumor tissue biopsies are obtained at diagnosis and after the investigation treatment, along with other biospecimens and radiographic exams. Thus, this study design can characterize the safety profiles, pharmacodynamics, and initial tumor responses to novel therapies in a treatment-naïve subject. Early window studies have also identified potential biomarkers to predict sensitivity or resistance to treatments. However, these early investigations have revealed multiple challenges associated with this trial design. In this review, we discuss recent window of opportunity trials in HNSCC and how they inform design considerations for future studies.

Keywords

Window of opportunity trial / head and neck cancer / biomarker / translational research / preoperative / oncology / trials

References

[1] Siegel RL,Jemal A.Cancer statistics, 2018..CA Cancer J Clin2018;68:7-30

[2] Pulte D.Changes in survival in head and neck cancers in the late 20th and early 21st century: a period analysis..Oncologist2010;15:994-1001 PMCID:PMC3228039

[3] Kalinsky K.Cracking open window of opportunity trials..J Clin Oncol2012;30:2573-5

[4] Cancer Genome Atlas NComprehensive genomic characterization of head and neck squamous cell carcinomas..Nature2015;517:576-82 PMCID:PMC4311405

[5] Hoesli RC,Michmerhuizen NL,Spector ME.Genomic sequencing and precision medicine in head and neck cancers..Eur J Surg Oncol2017;43:884-92 PMCID:PMC5393934

[6] Stransky N,Tward AD,Cibulskis K.The mutational landscape of head and neck squamous cell carcinoma..Science2011;333:1157-60 PMCID:PMC3415217

[7] Chung CH,McGavran L,Parker J.Increased epidermal growth factor receptor gene copy number is associated with poor prognosis in head and neck squamous cell carcinomas..J Clin Oncol2006;24:4170-6

[8] Bonner JA,Giralt J,Shin DM.Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck..N Engl J Med2006;354:567-78

[9] Schmitz S,Reychler H,Weynand B.Tumour response and safety of cetuximab in a window pre-operative study in patients with squamous cell carcinoma of the head and neck..Ann Oncol2013;24:2261-6

[10] Ferris RL,Trivedi S,Concha-Benavente F.Correlation of anti-tumor adaptive immunity with clinical response in a phase II "window" trial of neoadjuvant cetuximab in ptaients with resectable stage III-IV head and neck squamous carcinoma (HNSCC)..J Clin Oncol2016;34:6060

[11] Srivastava RM,Concha-Benavente F,Wang L.STAT1-Induced HLA Class I Upregulation Enhances Immunogenicity and Clinical Response to Anti-EGFR mAb Cetuximab Therapy in HNC Patients..Cancer Immunol Res2015;3:936-45 PMCID:PMC4526378

[12] Thomas F,Benlyazid A,Rives M.Pilot study of neoadjuvant treatment with erlotinib in nonmetastatic head and neck squamous cell carcinoma..Clin Cancer Res2007;13:7086-92

[13] Gross ND,Gooding WE,Thomas SM.Erlotinib, erlotinib-sulindac versus placebo: a randomized, double-blind, placebo-controlled window trial in operable head and neck cancer..Clin Cancer Res2014;20:3289-98 PMCID:PMC4104657

[14] Bauman JE,Gooding WE,Gross ND.Randomized, placebo-controlled window trial of EGFR, Src, or combined blockade in head and neck cancer..JCI Insight2017;2:e90449 PMCID:PMC5358497

[15] Machiels JP,Menis J,Fortpied C.Activity and safety of afatinib in a window preoperative EORTC study in patients with squamous cell carcinoma of the head and neck (SCCHN)..Ann Oncol2018;29:985-91

[16] Uppaluri R,Lin T,Haughey BH.Biomarker and Tumor Responses of Oral Cavity Squamous Cell Carcinoma to Trametinib: A Phase II Neoadjuvant Window-of-Opportunity Clinical Trial..Clin Cancer Res2017;23:2186-94 PMCID:PMC5509449

[17] Day TA,O'Brien PE,Godwin KB.Inhibition of mTOR Signaling and Clinical Activity of Rapamycin in Head and Neck Cancer in a Window of Opportunity Trial..Clin Cancer Res2019;25:1156-64 PMCID:PMC6377824

[18] Ferris RL.Immunology and Immunotherapy of Head and Neck Cancer..J Clin Oncol2015;33:3293-304 PMCID:PMC4586169

[19] Ferris RL,Fayette J,Colevas AD.Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck..N Engl J Med2016;375:1856-67

[20] 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

[21] Timar J,Forster-Horvath C,Dome B.Neoadjuvant immunotherapy of oral squamous cell carcinoma modulates intratumoral CD4/CD8 ratio and tumor microenvironment: a multicenter phase II clinical trial..J Clin Oncol2005;23:3421-32

[22] Wolf GT,Dolan RW,Kaplan MJ.Novel neoadjuvant immunotherapy regimen safety and survival in head and neck squamous cell cancer..Head Neck2011;33:1666-74 PMCID:PMC4062188

[23] Berinstein NL,Nguyen A,Wolf GT.Increased immune infiltration and chemokine receptor expression in head and neck epithelial tumors after neoadjuvant immunotherapy with the IRX-2 regimen..Oncoimmunology2018;7:e1423173 PMCID:PMC5927542

[24] 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

[25] Ferris RL,Baxi SS,Gauthier H.LBA46 - an 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..Ann Oncol2017;28:v605-v49

[26] Colevas AD,Chang S,Chatterjee S.A study to evaluate immunological response to PD-1 inhibition in squamous cell carcinoma of the head and neck (SCCHN) using novel PET imaging with [18F]F-AraG..J Clin Oncol2018;36:6050

[27] 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

[28] Shayan G,Gibson SP,Bryan JK.Phase Ib Study of Immune Biomarker Modulation with Neoadjuvant Cetuximab and TLR8 Stimulation in Head and Neck Cancer to Overcome Suppressive Myeloid Signals..Clin Cancer Res2018;24:62-72 PMCID:PMC5754237

[29] Rego DF,Elias ST,Guerra EN.Effects of metformin on head and neck cancer: a systematic review..Oral Oncol2015;51:416-22

[30] Curry J,Tassone P,Menezes DW.Metformin effects on head and neck squamous carcinoma microenvironment: Window of opportunity trial..Laryngoscope2017;127:1808-15 PMCID:PMC5515672

[31] Schmitz S,Locati LD.Perspectives on window of opportunity trials in head and neck cancer: lessons from the EORTC 90111-24111-NOCI-HNCG study..Eur J Cancer2018;104:219-23

[32] Spector ME,Haring CT,Birkeland AC.The potential for liquid biopsies in head and neck cancer..Discov Med2018;25:251-7 PMCID:PMC6125134

[33] Baxi SS,Burtness BA.Amidst the excitement: A cautionary tale of immunotherapy, pseudoprogression and head and neck squamous cell carcinoma..Oral Oncol2016;62:147-8

[34] Hanna GJ,Zolkind P.Rationale for neoadjuvant immunotherapy in head and neck squamous cell carcinoma..Oral Oncol2017;73:65-9

[35] Saada-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

[36] Schmitz S,Machiels JP.Window of opportunity studies: Do they fulfil our expectations?.Cancer Treat Rev2016;43:50-7

[37] Primdahl H,Larsen S,Ipsen M.Changes from 1992 to 2002 in the pretreatment delay for patients with squamous cell carcinoma of larynx or pharynx: a Danish nationwide survey from DAHANCA..Acta Oncol2006;45:156-61

[38] Esserman LJ.Accelerating identification and regulatory approval of investigational cancer drugs..JAMA2011;306:2608-9