ImportanceLocoregionally 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. ObjectiveTo
assess whether afatinib therapy after definitive chemoradiotherapy (CRT) improves
disease-free survival (DFS) in patients with HNSCC. Design, Setting, and ParticipantsThis
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. InterventionsPatients
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. Main Outcomes and MeasuresThe 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. ResultsA 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). Conclusions and RelevanceThis 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.
Trial RegistrationClinicalTrials.gov identifier: NCT01345669
