Checkpoint Inhibitors in Head and Neck Cancer: Rationale, Clinical Activity, and Potential Biomarkers
- 1.5k Downloads
The discovery and antibody targeting of immune regulatory molecules such as programmed cell death protein 1 (PD-1) and cytotoxic T lymphocyte antigen 4 (CTLA-4) pathways have led to clinically meaningful anti-cancer results. Rapid advances are being made in a variety of tumor types resulting in regulatory approvals in melanoma, non small cell lung cancer, and renal cell cancer. Numerous ongoing studies are expected to establish the worth of PD-1 pathway inhibitors in other tumor types as well as in combinations with approved agents. Head and neck squamous cell carcinoma (HNSCC) represents a complex group of malignancies characterized by profound immunosuppression and is an excellent candidate for investigation in this exciting field. However, given the fact that a subset of patients will likely benefit, it is critical to focus on biomarker development for appropriate patient selection and facilitation of trial design. As immunotherapy is settling in cancer treatment, immune checkpoint inhibitors are emerging as one of the most promising agents.
KeywordsPD-1 CTLA-4 PD-L1 Head and neck cancer Biomarkers Monoclonal antibodies
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
References and Recommended Reading
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 1.Coley WB, The treatment of malignant tumors by repeated inoculations of erysipelas. With a report of ten original cases. 1893. Clin Orthop Relat Res. 1991;3–11.Google Scholar
- 3.Finn OJ. Immuno-oncology: understanding the function and dysfunction of the immune system in cancer. Ann Oncol. 2012;23 Suppl 8:viii6-9.Google Scholar
- 4.••Atkins MB, Larkin J. Immunotherapy combined or sequenced with targeted therapy in the treatment of solid tumors: current perspectives. J Natl Cancer Inst. 2016;108. Excellent review on cancer immunotherapy.Google Scholar
- 9.Srivastava RM, Lee SC, Andrade Filho PA, Lord CA, Jie HB, Davidson HC, et al. Cetuximab-activated natural killer and dendritic cells collaborate to trigger tumor antigen-specific T-cell immunity in head and neck cancer patients. Clin Cancer Res. 2013;19:1858–72.CrossRefPubMedPubMedCentralGoogle Scholar
- 20.Brahmer JR, Drake CG, Wollner I, Powderly JD, Picus J, Sharfman WH, et al. Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates. J Clin Oncol. 2010;28:3167–75.CrossRefPubMedPubMedCentralGoogle Scholar
- 22.•BB, Seiwert TY, Weiss J. et al., A phase Ib study of MK-3475 in patients with human papillomavirus (HPV)-associated and non-HPV–associated head and neck (H/N) cancer. J Clin Oncol. 2014; 32: [suppl; abstr 6011] (2014). Evaluation of pembrolizumab in HPV(+) as opposed to HPV (−) patients in HNSCC.Google Scholar
- 23.••G.S. Seiwert TY HR, Mehra R, Tahara M, Berger R, Lee SH, Burtness B, Le DT, Heath K, Blum A, Dolled-Filhart M, Emancipator K, Pathiraja K, Cheng JD, Chow LQ. Antitumor activity and safety of pembrolizumab in patients (pts) with advanced squamous cell carcinoma of the head and neck (SCCHN): preliminary results from KEYNOTE-012 expansion cohort. J Clin Oncol 2015;33 (suppl; abstr LBA6008) (2015). Phase I study of Pembrolizumab in HNSCC.Google Scholar
- 24.••BM, Fury M, Ou SH, Balmanoukian A, Hansen A, Massarelli E, Blake-Haskins A, Li X, Rebelatto M, Steele K, Robbins PB, Vasselli J, Sega NH, Clinical activity and safety of MEDI4736, an anti-PD-L1 antibody, In Head and neck cancer. ESMO Meeting 2014, Poster # 988PD [Abstract ID 5656] (2014). Phase I study of Durvalumab in HNSCC.Google Scholar
- 29.TF, Papadopoulos K, Hamid O, Xiao F, Steele KE, Rebelatto MC, Robbins PB, Karakunnel JJ, Lai DW, Mahipal A, A Phase I study to evaluate the safety and antitumor activity of durvalumab (MEDI4736) in combination with tremelimumab in patients with advanced solid tumors. Journal for ImmunoTher Cancer. 2015; 3(Suppl 2):P165.Google Scholar
- 30.Shukuya T, Carbone DP. Predictive markers for the efficacy of anti-PD-1/PD-L1 antibodies in lung cancer. J Thorac Oncol. 2016.Google Scholar
- 35.OS, Fury M, BM, Balmanoukian A, Hansen A, Massarelli E, Blake-Haskins A, Li X, Rebelatto M, Steele K, Robbins PB, Vasselli J, Sega NH, Clinical activity and safety of MEDI4736, an anti-PD-L1 antibody, In Head and neck cancer. ESMO Meeting 2014;Poster # 988PD [Abstract ID 5656].Google Scholar
- 36.•Vassilakopoulou M, Avgeris M, Velcheti V, Kotoula V, Rampias T, Chatzopoulos K, et al. Evaluation of PD-L1 expression and associated tumor-infiltrating lymphocytes in laryngeal squamous cell carcinoma. Clin Cancer Res. 2016;22:704–13. Evaluation of PD-L1 expression with a subjective quantitative method.CrossRefPubMedGoogle Scholar
- 42.ZZ, Saloura V, Koeppen H, Keck MK, Khattri A, Boe M, Hegde PS, Xiao Y, Nakamura Y, Vokesm EE, De Souza JA, Villaflor VM, Kline J, Gajewski T, Lingen MW, Kowanetz M, Seiwert TY, Correlation of T-cell inflamed phenotype with mesenchymal subtype, expression of PD-L1, and other immune checkpoints in head and neck cancer. J Clin Oncol 2014;32:5s, 2014 (suppl; abstr 6009).Google Scholar