Combination of concurrent targeted and immune-therapy with nivolumab and cetuximab: new perspectives for squamous cell carcinoma treatment
https://doi.org/10.17650/2222-1468-2020-10-3-111-117
Abstract
Head and neck squamous cell carcinoma (HNSCC) is the most common cancer among head and neck malignancies and causes of cancer death. More than 50 % of patiens have relapses within first 3 years after treatment, with median survival less than 6 months. Cetuximab is the first targeted agent for HNSCC, is considered as alternative regiment in case of intolerance to platinum-based chemotherapy, and also can activate an antigenspecific T-cell immunity in head and neck cancer patients. Nivolumab is a check-point inhibitor, that improves overall survival of patients with advanced recurrent/metastatic HNSCC, due to the CheckMate-141 study results. The results of phase II study сoncurrent cetuximab and nivolumab in patients with recurrent and/or metastatic HNSCC showed a benefit for patients without prior check-point inhibitor exposure and overall well tolerated. Thus, we have 6 cases of HNSCC, treated with combination of nivolumab and cetuximab, resulted in durable (12 months) partial response or stabilization without severe adverse events. In our study, all 6 patients had prior check-point inhibitor exposure with nivolumab. Cetuximab was added to a treatment protocol after evidence-based progression during check-point inhibitor therapy. We demonstrate a case report of recurrent locally advanced HNSCC, treated with combination of nivolumab and cetuximab and resulted in stabilization. Only 1 patient had a progression after concurrent targeted and immune-therapy with nivolumab and cetuximab. New combination was well tolerated without severe adverse events. To our opinion, first results are challenging and we believe in great perspectives of comprehensive molecular profiling and combination of targeted and immune-therapy for better results.
About the Authors
A. M. MudunovRussian Federation
115478 Moscow, Kashirskoye Hwy, 24,
A. V. Ignatova
Russian Federation
Bld. 1, 2/1 Barrikadnaya St., Moscow 125993,
6 Miklukho-Maklaya St., Moscow 117198
A. S. Morozova
Russian Federation
6th km Pyatnitskoe Hwy, Krasnogorsky District, Moscow Region
S. O. Podvyaznikov
Russian Federation
Bld. 1, 2/1 Barrikadnaya St., Moscow 125993
Yu. V. Alymov
Russian Federation
115478 Moscow, Kashirskoye Hwy, 24
References
1. State of cancer care in Russia in 2019. Ed. by A.D. Kaprin, V.V. Starinsky, A.O. Shakhzadova. Moscow: P.A. Herzen MORI – branch of the NMRRC of the Ministry of Health of Russia, 2020. (In Russ.).
2. 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(19):1945–52. DOI: 10.1056/NEJMoa032641.
3. Pignon J.P., le Maître A., Maillard E., Bourhis J. 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. DOI: 10.1016/j.radonc.2009.04.014.
4. Cooper J.S., Pajak T.F., Forastiere A.A. et al. Postoperative concurrent radiotherapy and chemotherapy for highrisk squamous-cell carcinoma of the head and neck. N Engl J Med 2004;350(19):1937–44. DOI: 10.1056/NEJMoa032646.
5. Saloura V., Cohen E.E., Licitra L. et al. An open-label single-arm, phase II trial of zalutumumab, a human monoclonal anti-EGFR antibody, in patients with platinum-refractory squamous cell carcinoma of the head and neck. Cancer Chemother Pharmacol 2014;73:1227–39. DOI: 10.1007/s00280-014-2459-z.
6. Kuss I., Hathaway B., Ferris R.L. et al. Decreased absolute counts of T lymphocyte subsets and their relation to disease in squamous cell carcinoma of the head and neck. Clin Cancer Res 2004;10:3755–62. DOI: 10.1158/1078–0432.ccr-04-0054.
7. Topalian S.L., Drake C.G., Pardoll D.M. Immune checkpoint blockade: a common denominator approach to cancer therapy. Cancer Cell 2015;27:450–61. DOI: 10.1016/j.ccell.2015.03.001.
8. Concha-Benavente F., Srivastava R.M., Trivedi S. et al. Identification of the cellintrinsic and -extrinsic pathways downstream of EGFR and IFNγ that induce PD-L1 expression in head and neck cancer. Cancer Res 2016;76:1031–43. DOI: 10.1158/0008-5472.CAN-15-2001.
9. Li J., Jie H.B., Lei Y. et al. PD-1/SHP-2 inhibits Tc1/Th1 phenotypic responses and the activation of T cells in the tumor microenvironment. Cancer Res 2015;75: 508–18. DOI: 10.1158/0008-5472.CAN-14-1215.
10. Badoual C., Hans S., Merillon N. et al. PD-1-expressing tumor-infiltrating T cells are a favorable prognostic biomarker in HPV-associated head and neck cancer. Cancer Res 2013;73:128–38. DOI: 10.1158/0008-5472.CAN-12-2606.
11. Zandberg D.P., Strome S.E. The role of the PD-L1: PD-1 pathway in squamous cell carcinoma of the head and neck. Oral Oncol 2014;50:627–32. DOI: 10.1016/j.oraloncology.2014.04.003.
12. Parikh F., Duluc D., Imai N. et al. Chemoradiotherapy-induced upregulation of PD-1 antagonizes immunity to HPVrelated oropharyngeal cancer. Cancer Res 2014;74(24):7205–16. DOI: 10.1158/0008-5472.can-14-1913.
13. Gillison M.L., Blumenschein G. Jr, Fayette J. et al. Nivolumab in patients with recurrent or metastatic squamous cell carcinoma of the head and neck: efficacy and safety in CheckMate 141 by prior cetuximab use. Oncologist 2018;23(9):1079–82. DOI: 10.1634/theoncologist.2017-0674.
14. Ferris R.L., Blumenschein G. Jr, Fayette J. et al. Nivolumab for recurrent squamous cell carcinoma of the head and neck. N Engl J Med 2016;375(19):1856–67. DOI: 10.1056/NEJMoa1602252.
15. Srivastava R.M., Lee S.C., Andrade Filho P.A. et al. Cetuximab-activated natural killer and dendabstractritic cells collaborate to trigger tumor antigenspecific T-cell immunity in head and neck cancer patients. Clin Cancer Res 2013;19:1858–72.
16. Concha-Benavente F., Srivastava R.M., Trivedi S. et al. Identification of the cell intrinsic and extrinsic pathways downstream of EGFR and IFNγ that induce PD-L1 expression in head and neck cancer. Cancer Res 2016;76(5):1031–43.
17. Chung C.H., Bonomi M.R., Steuer C.E. et al. Concurrent cetuximab (CTX) and nivolumab (NIVO) in patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC): results of phase II study. J Clin Oncol 2020;38(15 Suppl):6515.
Review
For citations:
Mudunov A.M., Ignatova A.V., Morozova A.S., Podvyaznikov S.O., Alymov Yu.V. Combination of concurrent targeted and immune-therapy with nivolumab and cetuximab: new perspectives for squamous cell carcinoma treatment. Head and Neck Tumors (HNT). 2020;10(3):111-117. (In Russ.) https://doi.org/10.17650/2222-1468-2020-10-3-111-117