Low-dose Radiotherapy Plus Tislelizumab in Combination With Afatinib for Neoadjuvant Treatment of Surgically Resectable Head and Neck Squamous Carcinoma

Summary

The purpose of this study was to evaluate the safety and tolerability of low-dose radiotherapy plus tislelizumab in combination with afatinib neoadjuvant therapy for patients with surgically resectable squamous carcinoma of the head and neck.

Timeline

Start

2024-07-31

Primary completion

2025-04-10

Completion

2025-04-10

Publications

• Background Ferlay J, Colombet M, Soerjomataram I, Mathers C, Parkin DM, Pineros M, Znaor A, Bray F. Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods. Int J Cancer. 2019 Apr 15;144(8):1941-1953. doi: 10.1002/ijc.31937. Epub 2018 Dec 6.
• Background Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394-424. doi: 10.3322/caac.21492. Epub 2018 Sep 12.
• Background Pulte D, Brenner H. Changes in survival in head and neck cancers in the late 20th and early 21st century: a period analysis. Oncologist. 2010;15(9):994-1001. doi: 10.1634/theoncologist.2009-0289. Epub 2010 Aug 26.
• Background Denaro N, Merlano MC, Russi EG. Follow-up in Head and Neck Cancer: Do More Does It Mean Do Better? A Systematic Review and Our Proposal Based on Our Experience. Clin Exp Otorhinolaryngol. 2016 Dec;9(4):287-297. doi: 10.21053/ceo.2015.00976. Epub 2016 Jun 25.
• Background Harari PM. Promising new advances in head and neck radiotherapy. Ann Oncol. 2005;16 Suppl 6:vi13-vi19. doi: 10.1093/annonc/mdi453.
• Background Haddad R, O'Neill A, Rabinowits G, Tishler R, Khuri F, Adkins D, Clark J, Sarlis N, Lorch J, Beitler JJ, Limaye S, Riley S, Posner M. Induction chemotherapy followed by concurrent chemoradiotherapy (sequential chemoradiotherapy) versus concurrent chemoradiotherapy alone in locally advanced head and neck cancer (PARADIGM): a randomised phase 3 trial. Lancet Oncol. 2013 Mar;14(3):257-64. doi: 10.1016/S1470-2045(13)70011-1. Epub 2013 Feb 13.
• Background Cohen EE, Karrison TG, Kocherginsky M, Mueller J, Egan R, Huang CH, Brockstein BE, Agulnik MB, Mittal BB, Yunus F, Samant S, Raez LE, Mehra R, Kumar P, Ondrey F, Marchand P, Braegas B, Seiwert TY, Villaflor VM, Haraf DJ, Vokes EE. Phase III randomized trial of induction chemotherapy in patients with N2 or N3 locally advanced head and neck cancer. J Clin Oncol. 2014 Sep 1;32(25):2735-43. doi: 10.1200/JCO.2013.54.6309. Epub 2014 Jul 21.
• Background Geoffrois L, Martin L, De Raucourt D, Sun XS, Tao Y, Maingon P, Buffet J, Pointreau Y, Sire C, Tuchais C, Babin E, Coutte A, Rolland F, Kaminsky MC, Alfonsi M, Lapeyre M, Saliou M, Lafond C, Jadaud E, Gery B, Zawadi A, Tourani JM, Khoury C, Henry AR, Hasbini A, Guichard F, Borel C, Meert N, Guillet P, Calais MH, Garaud P, Bourhis J. Induction Chemotherapy Followed by Cetuximab Radiotherapy Is Not Superior to Concurrent Chemoradiotherapy for Head and Neck Carcinomas: Results of the GORTEC 2007-02 Phase III Randomized Trial. J Clin Oncol. 2018 Nov 1;36(31):3077-3083. doi: 10.1200/JCO.2017.76.2591. Epub 2018 Jul 17.
• Background Machiels JP, Haddad RI, Fayette J, Licitra LF, Tahara M, Vermorken JB, Clement PM, Gauler T, Cupissol D, Grau JJ, Guigay J, Caponigro F, de Castro G Jr, de Souza Viana L, Keilholz U, Del Campo JM, Cong XJ, Ehrnrooth E, Cohen EE; LUX-H&N 1 investigators. Afatinib versus methotrexate as second-line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck progressing on or after platinum-based therapy (LUX-Head & Neck 1): an open-label, randomised phase 3 trial. Lancet Oncol. 2015 May;16(5):583-94. doi: 10.1016/S1470-2045(15)70124-5. Epub 2015 Apr 16.
• Background Guo Y, Ahn MJ, Chan A, Wang CH, Kang JH, Kim SB, Bello M, Arora RS, Zhang Q, He X, Li P, Dechaphunkul A, Kumar V, Kamble K, Li W, Kandil A, Cohen EEW, Geng Y, Zografos E, Tang PZ. Afatinib versus methotrexate as second-line treatment in Asian patients with recurrent or metastatic squamous cell carcinoma of the head and neck progressing on or after platinum-based therapy (LUX-Head & Neck 3): an open-label, randomised phase III trial. Ann Oncol. 2019 Nov 1;30(11):1831-1839. doi: 10.1093/annonc/mdz388.
• Background Burtness B, Haddad R, Dinis J, Trigo J, Yokota T, de Souza Viana L, Romanov I, Vermorken J, Bourhis J, Tahara M, Martins Segalla JG, Psyrri A, Vasilevskaya I, Nangia CS, Chaves-Conde M, Kiyota N, Homma A, Holeckova P, Del Campo JM, Asarawala N, Nicolau UR, Rauch D, Even C, Wang B, Gibson N, Ehrnrooth E, Harrington K, Cohen EEW; LUX-Head & Neck 2 investigators. Afatinib vs Placebo as Adjuvant Therapy After Chemoradiotherapy in Squamous Cell Carcinoma of the Head and Neck: A Randomized Clinical Trial. JAMA Oncol. 2019 Aug 1;5(8):1170-1180. doi: 10.1001/jamaoncol.2019.1146.
• Background Machiels JP, Bossi P, Menis J, Lia M, Fortpied C, Liu Y, Lhommel R, Lemort M, Schmitz S, Canevari S, De Cecco L, Guzzo M, Bianchi R, Quattrone P, Crippa F, Duprez T, Lalami Y, Quiriny M, de Saint Aubain N, Clement PM, Coropciuc R, Hauben E, Licitra LF. Activity and safety of afatinib in a window preoperative EORTC study in patients with squamous cell carcinoma of the head and neck (SCCHN). Ann Oncol. 2018 Apr 1;29(4):985-991. doi: 10.1093/annonc/mdy013.
• Background Ferris RL, Blumenschein G Jr, Fayette J, Guigay J, Colevas AD, Licitra L, Harrington K, Kasper S, Vokes EE, Even C, Worden F, Saba NF, Iglesias Docampo LC, Haddad R, Rordorf T, Kiyota N, Tahara M, Monga M, Lynch M, Geese WJ, Kopit J, Shaw JW, Gillison ML. Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck. N Engl J Med. 2016 Nov 10;375(19):1856-1867. doi: 10.1056/NEJMoa1602252. Epub 2016 Oct 8.
• Background Karam SD, Raben D. Radioimmunotherapy for the treatment of head and neck cancer. Lancet Oncol. 2019 Aug;20(8):e404-e416. doi: 10.1016/S1470-2045(19)30306-7. Epub 2019 Jul 29.
• Background Lee NCJ, Kelly JR, Park HS, An Y, Judson BL, Burtness BA, Husain ZA. Patterns of failure in high-metastatic node number human papillomavirus-positive oropharyngeal carcinoma. Oral Oncol. 2018 Oct;85:35-39. doi: 10.1016/j.oraloncology.2018.08.001. Epub 2018 Aug 20.
• Background Cooper JS, Pajak TF, Forastiere AA, Jacobs J, Campbell BH, Saxman SB, Kish JA, Kim HE, Cmelak AJ, Rotman M, Machtay M, Ensley JF, Chao KS, Schultz CJ, Lee N, Fu KK; Radiation Therapy Oncology Group 9501/Intergroup. Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med. 2004 May 6;350(19):1937-44. doi: 10.1056/NEJMoa032646.
• Background Bernier J, Domenge C, Ozsahin M, Matuszewska K, Lefebvre JL, Greiner RH, Giralt J, Maingon P, Rolland F, Bolla M, Cognetti F, Bourhis J, Kirkpatrick A, van Glabbeke M; European Organization for Research and Treatment of Cancer Trial 22931. Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med. 2004 May 6;350(19):1945-52. doi: 10.1056/NEJMoa032641.
• Background Leidner R, Crittenden M, Young K, Xiao H, Wu Y, Couey MA, Patel AA, Cheng AC, Watters AL, Bifulco C, Morris G, Rushforth L, Nemeth S, Urba WJ, Gough M, Bell RB. Neoadjuvant immunoradiotherapy results in high rate of complete pathological response and clinical to pathological downstaging in locally advanced head and neck squamous cell carcinoma. J Immunother Cancer. 2021 May;9(5):e002485. doi: 10.1136/jitc-2021-002485.
• Background He K, Barsoumian HB, Bertolet G, Verma V, Leuschner C, Koay EJ, Ludmir EB, Hsu E, Pisipati E, Voss TA, Puebla-Osorio N, Cortez MA, Welsh JW. Novel Use of Low-Dose Radiotherapy to Modulate the Tumor Microenvironment of Liver Metastases. Front Immunol. 2021 Dec 15;12:812210. doi: 10.3389/fimmu.2021.812210. eCollection 2021.
• Background Barsoumian HB, Ramapriyan R, Younes AI, Caetano MS, Menon H, Comeaux NI, Cushman TR, Schoenhals JE, Cadena AP, Reilly TP, Chen D, Masrorpour F, Li A, Hong DS, Diab A, Nguyen QN, Glitza I, Ferrarotto R, Chun SG, Cortez MA, Welsh J. Low-dose radiation treatment enhances systemic antitumor immune responses by overcoming the inhibitory stroma. J Immunother Cancer. 2020 Oct;8(2):e000537. doi: 10.1136/jitc-2020-000537.

Drugs

Indications