2018-19 Section 7-Neoplastic and Inflammatory Diseases of the Head and Neck eBook

Immunotherapy for recurrent/metastatic head and neck cancer Alfieri et al.

Table 1. Ongoing clinical trials exploring loco-regional immunotherapy-based approaches in recurrent/metastatic HNSCC

Study

ClinicalTrials.gov reference

TLR8 Agonist VTX-2337 and Cetuximab in Treating Patients With Locally Advanced, Recurrent, or Metastatic Squamous Cell Cancer of Head and Neck Personalized and Cell-based Antitumor Immunization MVX-ONCO-1 in Advanced HNSCC

NCT01334177

NCT02999646 NCT01984892 NCT02521870

Treatment of Solid Tumors With Intratumoral Hiltonol (Poly-ICLC)

A Trial of Intratumoral Injections of SD-101 in Combination With Pembrolizumab in Patients With Metastatic Melanoma or Recurrent or Metastatic Head and Neck

A Phase 1/2 Safety Study of Intratumorally Dosed INT230–6

NCT03058289 NCT02626000

Talimogene Laherparepvec With Pembrolizumab for Recurrent Metastatic Squamous Cell Carcinoma of the Head and Neck Immunotherapy Using Tumor Infiltrating Lymphocytes for Patients With Metastatic Human Papillomavirus-Associated Cancers

NCT01585428

T Cell Receptor Immunotherapy Targeting HPV-16 E6 for HPV-Associated Cancers Vaccine Therapy in Treating Patients With Stage IV Head and Neck Cancer

NCT02280811 NCT00021424 NCT02624999

Study Comparing AlloVax to Chemotherapy in Recurrent/Metastatic Squamous Cell Carcinoma of the Head & Neck

CONCLUSION To date, all published data of immunotherapy refer to recurrent/metastatic HNSCC patients progressing after platinum-based regimens. There is a clear ben- efit in term of ORR and OS. Safety was also better than chemotherapy. The profile of the immune- related side-effects in HNSCC was characterized by higher rates of endocrine disorders (e.g. hypothy- roidism, possibly due to previous radiotherapy) and lower percentage of pneumonitis [21 & ]. Checkpoint inhibitors demonstrated benefit in second-line R/M HNSCC thus changing the state of the art approach in this patient’s setting. Phase III studies are ongoing in first line where SOC [chemotherapy with cis- platin (CDDP) in addition to 5-fluorouracil (5-FU) plus cetuximab] is compared with immunotherapy, both in combination with chemotherapy (CDDP þ 5-FU) or with multiple immune checkpoint inhib- itors. Preliminary data are awaited for 2018. At present, immunotherapy works in a minor propor- tion of HNSCC patients. Therefore, current and future studies are being carried out to identify the immune responders’ profile, which includes bio- markers as well as clinical parameters.

Conflicts of interest L.L. declared no specific conflicts of interest with this work. S.C and S.A. declared no conflicts of interest. REFERENCES AND RECOMMENDED READING Papers of particular interest, published within the annual period of review, have been highlighted as: & of special interest && of outstanding interest 1. Bossi P, Alfieri S. Investigational drugs for head and neck cancer. Expert Opin Investig Drugs 2016; 25:797–810. 2. Vermorken JB, Mesia R, Rivera F, et al. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med 2008; 359:1116–1127. 3. Pignon JP, le Maıˆtre A, Maillard E, Bourhis J, et al., MACH-NC Collaborative Group. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): an update on 93 randomised trials and 17,346 patients. Radiother Oncol 2009; 92:4–14. 4. Bernier J, Domenge C, Ozsahin M, et al. Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med 2004; 350:1945–1952. 5. Cooper JS, Pajak TF, Forastiere AA, et al. Postoperative concurrent radio- therapy and chemotherapy for high-risk squamous cell carcinoma of the head and neck. N Engl J Med 2004; 350:1937–1944. 6. Siano M, Infante G, Resteghini C, et al. Outcome of recurrent and metastatic head and neck squamous cell cancer patients after first line platinum and cetuximab therapy. Oral Oncol 2017; 69:33–37. 7. De Stefani A, Forni G, Ragona R, et al. Improved survival with perilymphatic interleukin-2 in patients with resectable squamous cell carcinoma of the oral cavity and the oropharynx. Cancer 2002; 95:90–97. 8. Ferris RL. Immunology and immunotherapy of head and neck cancer. J Clin Oncol 2015; 33:3293–3304. 9. && Ferris RL, Blumenschein G Jr, Fayette J, et al. Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med 2016; 375: 1856–1867. This was the pivotal trial of nivolumab in HNSCC. 10. Licitra L, Ferris R, Blumenschein G Jr, et al. Nivolumab vs investigator’s choice in patients with recurrent or metastatic squamous cell carcinoma of the head and neck: treatment effect on clinical outcomes by best overall response in CheckMate141. Ann Oncol 2017; 28(Suppl_5):v372–v394. 11. Ferris R, Licitra L, Fayette J, et al. Nivolumab (NIVO) vs investigator’s choice (IC) in patients with recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck: efficacy and safety in CheckMate 141 by prior cetuximab use. J Clin Oncol 2017; 35(15 Suppl):6020–16020. 12. Haddad R, Blumenschein G Jr, Fayette J, et al. Treatment beyond progression with nivolumab in patients with recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN) in the phase 3 CheckMate 141 study: a biomarker analysis and updated clinical outcomes. Ann Oncol 2017; 28(Suppl 5); mdx 374.001.

Acknowledgements None.

Financial support and sponsorship L.L. reported personal fees as consulting role from Roche, Bristol-Myers Squibb, Novartis, Merck Sharp and Dohme, AstraZeneca, Bayer, Boehringer Ingelheim, Eisai, Merck Serono, Sobi and DEBIOPHARM, outside the submitted work.

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