Afatinib vs Placebo as Adjuvant Therapy After Chemoradiotherapy in Squamous Cell Carcinoma of the Head and Neck: A Randomized Clinical Trial.

Details

Serval ID
serval:BIB_DF0BB6817B7E
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Afatinib vs Placebo as Adjuvant Therapy After Chemoradiotherapy in Squamous Cell Carcinoma of the Head and Neck: A Randomized Clinical Trial.
Journal
JAMA oncology
Author(s)
Burtness B., Haddad R., Dinis J., Trigo J., Yokota T., de Souza Viana L., Romanov I., Vermorken J., Bourhis J., Tahara M., Martins Segalla J.G., Psyrri A., Vasilevskaya I., Nangia C.S., Chaves-Conde M., Kiyota N., Homma A., Holeckova P., Del Campo J.M., Asarawala N., Nicolau U.R., Rauch D., Even C., Wang B., Gibson N., Ehrnrooth E., Harrington K., Cohen EEW
Working group(s)
LUX-Head & Neck 2 investigators
ISSN
2374-2445 (Electronic)
ISSN-L
2374-2437
Publication state
Published
Issued date
01/08/2019
Peer-reviewed
Oui
Volume
5
Number
8
Pages
1170-1180
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
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.
ClinicalTrials.gov identifier: NCT01345669.
Pubmed
Web of science
Open Access
Yes
Create date
30/06/2019 15:49
Last modification date
22/05/2021 5:34
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