RT Journal Article
T1 Afatinib vs Placebo as Adjuvant Therapy After Chemoradiotherapy in Squamous Cell Carcinoma of the Head and Neck: A Randomized Clinical Trial.
A1 Burtness, Barbara
A1 Haddad, Robert
A1 Dinis, Jose
A1 Trigo, Jose
A1 Yokota, Tomoya
A1 de-Souza-Viana, Luciano
A1 Romanov, Ilya
A1 Vermorken, Jan
A1 Bourhis, Jean
A1 Tahara, Makoto
A1 Martins-Segalla, Jose Getulio
A1 Psyrri, Amanda
A1 Vasilevskaya, Irina
A1 Nangia, Chaitali Singh
A1 Chaves-Conde, Manuel
A1 Kiyota, Naomi
A1 Homma, Akihiro
A1 Holeckova, Petra
A1 Del-Campo, Josep Maria
A1 Asarawala, Nirav
A1 Nicolau, Ulisses Ribaldo
A1 Rauch, Daniel
A1 Even, Caroline
A1 Wang, Bushi
A1 Gibson, Neil
A1 Ehrnrooth, Eva
A1 Harrington, Kevin
A1 Cohen, Ezra E W
K1 Carboplatin
K1 Squamous Cell Carcinoma of Head and Neck
K1 Disease-Free Survival
K1 Hypopharynx
K1 Neoplasm Recurrence, Local
AB Locoregionally advanced head and neck squamous cell cancer (HNSCC) is treated curatively; however, risk of recurrence remains high among some patients. The ERBB family blocker afatinib has shown efficacy in recurrent or metastatic HNSCC. To assess whether afatinib therapy after definitive chemoradiotherapy (CRT) improves disease-free survival (DFS) in patients with HNSCC. This multicenter, phase 3, double-blind randomized clinical trial (LUX-Head & Neck 2) studied 617 patients from November 2, 2011, to July 4, 2016. Patients who had complete response after CRT, comprising radiotherapy with cisplatin or carboplatin, with or without resection of residual disease, for locoregionally advanced high- or intermediate-risk HNSCC of the oral cavity, hypopharynx, larynx, or oropharynx were included in the study. Data analysis was of the intention-to-treat population. Patients were randomized (2:1) to treatment with afatinib (40 mg/d) or placebo, stratified by nodal status (N0-2a or N2b-3) and Eastern Cooperative Oncology Group performance status (0 or 1). Treatment continued for 18 months or until disease recurrence, unacceptable adverse events, or patient withdrawal. The primary end point was DFS, defined as time from the date of randomization to the date of tumor recurrence or secondary primary tumor or death from any cause. Secondary end points were DFS at 2 years, overall survival (defined as time from the date of randomization to death), and health-related quality of life. A total of 617 patients were studied (mean [SD] age, 58 [8.4] years; 528 male [85.6%]). Recruitment was stopped after a preplanned interim futility analysis on July 4, 2016, on recommendation from an independent data monitoring committee. Treatment was discontinued. Median DFS was 43.4 months (95% CI, 37.4 months to not estimable) in the afatinib group and not estimable (95% CI, 40.1 months to not estimable) in the placebo group (hazard ratio, 1.13; 95% CI, 0.81-1.57; stratified log-rank test P = .48). The most common grade 3 and 4 drug-related adverse effects were acneiform rash (61 [14.8%] of 411 patients in the afatinib group vs 1 [0.5%] of 206 patients in the placebo group), stomatitis (55 [13.4%] in the afatinib group vs 1 [0.5%] in the placebo group), and diarrhea (32 [7.8%] in the afatinib group vs 1 [0.5%] in the placebo group). This study's findings indicate that treatment with afatinib after CRT did not improve DFS and was associated with more adverse events than placebo in patients with primary, unresected, clinically high- to intermediate-risk HNSCC. The use of adjuvant afatinib after CRT is not recommended. 
PB American Medical Association
YR 2019
FD 2019-06-13
LK http://hdl.handle.net/10668/14105
UL http://hdl.handle.net/10668/14105
LA en
NO Burtness B, Haddad R, Dinis J, Trigo J, Yokota T, de Souza Viana L, et al. 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
DS RISalud
RD Apr 6, 2025