Head and Neck

Immune-Mediated Approaches to Head and Neck Cancer

UNMET NEED

Head and neck cancer is the eighth most common cancer in the United States3,4

HNSCC has traditionally 2 distinct etiologies with different biological and clinical characteristics. Amongst the patients tested for human papillomavirus (HPV):

Patients with HPV positive locally advanced HNSCC demonstrate significantly better prognosis.7-11

Management goals in HNSCC depend on disease stage12

Early stage or locally advanced disease

Treatment goal is cure and is typically composed of a combination of surgery, radiation therapy, and chemotherapy

Recurrent or metastatic HNSCC

Treatment of recurrent/metastatic disease depends on performance status. While enrollment in a clinical trial is the preferred option, treatment options for recurrent/metastatic HNSCC include a platinum-based combination chemotherapy regimen, single agent chemotherapy, and immunotherapy if disease progresses on or after platinum-containing chemotherapy

Outcomes for patients with recurrent or metastatic HNSCC remain poor

Median overall survival (OS) in first-line recurrent/metastatic is 10.1 months2

Currently, non-chemotherapy based regimens do not exist in the first-line recurrent/metastatic HNSCC setting. Because chemotherapy is associated with acute toxicity concerns and poor outcomes, there is a need for novel approaches to treating recurrent/metastatic HNSCC.2

HARNESSING THE IMMUNE SYSTEM

Head and neck cancer has the seventh highest mutational burden among tumor types13

Several immune-based approaches are being explored18

vaccine

Therapeutic vaccines

Cell-based therapy that activates cytotoxic T cells and induces the production of antibodies by introducing antigens into a patient

vaccine

Adoptive cell therapy (eg, CAR-T)

Selecting and engineering T cells for high tumor specificity ex vivo, then reintroduced into the patient

vaccine

Immune checkpoint inhibitors

Targets key immune checkpoints to harness the innate immune response to eliminate tumor cells

Evading immune inhibition with the immune checkpoint blockade

Because tumors may induce tolerance among tumor-specific T cells and create an immunosuppressive microenvironment, the immune checkpoint blockade may help to restore the patient’s preexisting immune response. Antitumor immune responses can be activated by blocking these immune-inhibitory pathways, including the checkpoint proteins of PD-L1 and CTLA-4.18-20

Durable response could be achieved by disrupting multiple pathways

Disrupting multiple, non-redundant immune pathways such as CTLA-4 and PD-L1 may offer synergistic antitumor effects. Complementary inhibition enhances T-cell activation, proliferation, and differentiation into memory T cells. The formation of memory T cells may promote durable antitumor response.21-23

Immunotherapy is changing the treatment landscape

In 2016, two immune checkpoint inhibitors were approved for use after platinum failure for patients with recurrent/metastatic HNSCC.

AstraZeneca is currently investigating combination immunotherapy for both first-line and second-line treatment of HNSCC. By targeting multiple checkpoint receptors, immunotherapy may provide synergistic and additive benefits for a broader patient population, with antitumor properties and improved durability of response.24,25

REVIEW our immuno-oncology clinical trials for HNSCC

CAR-T=chimeric antigen receptor T cell therapy; PD-1=programmed cell death-1; PD-L1=programmed cell death ligand-1; CTLA-4=cytotoxic T-lymphocyte–associated antigen 4.

NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

References

1. Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin. 2017;67(1):7-30. 2. Vermorken JB, Mesia R, Rivera F, et al. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med. 2008;359(11):1116-1127. 3. National Cancer Institute. Cancer stat facts: oral cavity and pharynx cancer. https://seer.cancer.gov/statfacts/html/oralcav.html. Accessed June 26, 2017. 4. National Cancer Institute. Cancer stat facts: esophageal cancer. https://seer.cancer.gov/statfacts/html/esoph.html. Accessed June 26, 2017. 5. Cancer.net. Head and neck cancer: statistics. http://www.cancer.net/cancer-types/head-and-neck-cancer/statistics. Accessed June 26, 2017. 6. Treatment Architecture: United States Head and Neck Cancer. CancerMPact® United States, 2016 © Kantar Health. October 2016. 7. Ang KK, Harris J, Wheeler R, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med. 2010;363(1):24-35. 8. Fakhry C, Westra WH, Li S, et al. Improved survival of patients with human papillomavirus-positive head and neck squamous cell carcinoma in a prospective clinical trial. J Natl Cancer Inst. 2008;100(4):261–269. 9. Fakhry C, Zhang Q, Nguyen-tan PF, et al. Human papillomavirus and overall survival after progression of oropharyngeal squamous cell carcinoma. J Clin Oncol. 2014;32(30):3365-3373. 10. Posner MR, Lorch JH, Goloubeva O, et al. Survival and human papillomavirus in oropharynx cancer in TAX 324: a subset analysis from an international phase III trial. Ann Oncol. 2011;22(5):1071-1077. 11. Rischin D, Young RJ, Fisher R, et al. Prognostic significance of p16INK4A and human papillomavirus in patients with oropharyngeal cancer treated on TROG 02.02 phase III trial. J Clin Oncol. 2010;28(27):4142-4148. 12. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Head and Neck Cancers v.2.2017. © National Comprehensive Cancer Network, Inc. 2017. All rights reserved. Accessed May 24, 2017. To view the most recent and complete version of the guidelines, go online to NCCN.org. 13. Rajasagi M, Shukla SA, Fritsch EF, et al. Systematic identification of personal tumor-specific neoantigens in chronic lymphocytic leukemia. Blood. 2014;124(3):453-462. 14. Rizvi NA, Hellmann MD, Snyder A, et al. Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science. 2015;348(6230):124-128. 15. Partlová S, Boucek J, Kloudová K, et al. Distinct patterns of intratumoral immune cell infiltrates in patients with HPV-associated compared to nonvirally induced head and neck squamous cell carcinoma. Oncoimmunology 2015;4(1):e965570. 16. Russell S, Angell T, Lechner M, et al. Immune cell infiltration patterns and survival in head and neck squamous cell carcinoma. Head Neck Oncol. 2013;5(3):24. 17. Schoenfeld JD. Immunity in head and neck cancer. Cancer Immunol Res. 2015;3(1):12-17. 18. Farkona S, Diamandis EP, Blasutig IM. Cancer immunotherapy: the beginning of the end of cancer? BMC Med. 2016;14:73. 19. Madureira P, de Mello RA, de Vasconcelos A, Zhang Y. Immunotherapy for lung cancer: for whom the bell tolls? Tumor Biol. 2015;36(3):1411-1422. 20. Adachi K, Tamada K. Immune checkpoint blockade opens an avenue of cancer immunotherapy with a potent clinical efficacy. Cancer Science. 2015;106(8):945-950. 21. Das R, Verma R, Sznol M, et al. Combination therapy with anti-CTLA-4 and anti-PD-1 leads to distinct immunologic changes in vivo. J Immunol. 2015;194(3):950-959. 22. Intlekofer AM, Thompson CB. At the bench: preclinical rationale for CTLA-4 and PD-1 blockade as cancer immunotherapy. J Leukoc Biol. 2013;94(1):25-39. 23. Drake CG. Combination immunotherapy approaches. Ann Oncol. 2012;23(suppl 8):viii41-viii46. 24. National Cancer Institute. Nivolumab improves survival for patients with recurrent head and neck cancer. https://www.cancer.gov/types/head-and-neck/research/nivolumab-hnscc. Accessed June 26, 2017. 25. National Cancer Institute. FDA approves pembrolizumab for head and neck cancer. https://www.cancer.gov/news-events/cancer-currents-blog/2016/fda-pembrolizumab-hnscc. Accessed June 26, 2017.