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Clinical Trial
. 2016 Aug;27(8):1585-93.
doi: 10.1093/annonc/mdw151. Epub 2016 Apr 15.

Afatinib versus methotrexate in older patients with second-line recurrent and/or metastatic head and neck squamous cell carcinoma: subgroup analysis of the LUX-Head & Neck 1 trial

P M Clement  1 , T Gauler  2 , J P Machiels  3 , R I Haddad  4 , J Fayette  5 , L F Licitra  6 , M Tahara  7 , E E W Cohen  8 , D Cupissol  9 , J J Grau  10 , J Guigay  11 , F Caponigro  12 , G de Castro Jr  13 , L de Souza Viana  14 , U Keilholz  15 , J M Del Campo  16 , X J Cong  17 , E Ehrnrooth  18 , J B Vermorken  19 ; LUX-H&N 1 investigators
Affiliations
Clinical Trial

Afatinib versus methotrexate in older patients with second-line recurrent and/or metastatic head and neck squamous cell carcinoma: subgroup analysis of the LUX-Head & Neck 1 trial

P M Clement et al. Ann Oncol. 2016 Aug.

Abstract

Background: In the phase III LUX-Head & Neck 1 (LHN1) trial, afatinib significantly improved progression-free survival (PFS) versus methotrexate in recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) patients progressing on/after platinum-based therapy. This report evaluates afatinib efficacy and safety in prespecified subgroups of patients aged ≥65 and <65 years.

Patients and methods: Patients were randomized (2:1) to 40 mg/day oral afatinib or 40 mg/m(2)/week intravenous methotrexate. PFS was the primary end point; overall survival (OS) was the key secondary end point. Other end points included: objective response rate (ORR), patient-reported outcomes, tumor shrinkage, and safety. Disease control rate (DCR) was also assessed.

Results: Of 483 randomized patients, 27% (83 afatinib; 45 methotrexate) were aged ≥65 years (older) and 73% (239 afatinib; 116 methotrexate) <65 years (younger) at study entry. Similar PFS benefit with afatinib versus methotrexate was observed in older {median 2.8 versus 2.3 months, hazard ratio (HR) = 0.68 [95% confidence interval (CI) 0.45-1.03], P = 0.061} and younger patients [2.6 versus 1.6 months, HR = 0.79 (0.62-1.01), P = 0.052]. In older and younger patients, the median OS with afatinib versus methotrexate was 7.3 versus 6.4 months [HR = 0.84 (0.54-1.31)] and 6.7 versus 6.2 months [HR = 0.98 (0.76-1.28)]. ORRs with afatinib versus methotrexate were 10.8% versus 6.7% and 10.0% versus 5.2%; DCRs were 53.0% versus 37.8% and 47.7% versus 38.8% in older and younger patients, respectively. In both subgroups, the most frequent treatment-related adverse events were rash/acne (73%-77%) and diarrhea (70%-80%) with afatinib, and stomatitis (43%) and fatigue (31%-34%) with methotrexate. Fewer treatment-related discontinuations were observed with afatinib (each subgroup 7% versus 16%). A trend toward improved time to deterioration of global health status, pain, and swallowing with afatinib was observed in both subgroups.

Conclusions: Advancing age (≥65 years) did not adversely affect clinical outcomes or safety with afatinib versus methotrexate in second-line R/M HNSCC patients.

Clinical trial registration: NCT01345682 (ClinicalTrials.gov).

Keywords: HNSCC; afatinib; methotrexate; older; phase III; second-line.

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Figures

Figure 1.
Figure 1.
Kaplan–Meier estimates of (A) PFS and (B) OS by age subgroup. aStratified log-rank test. CI, confidence interval; HR, hazard ratio; OS, overall survival; PFS, progression-free survival.
Figure 2.
Figure 2.
Waterfall plot of maximum percentage tumor shrinkage in subgroups of patients aged (A) ≥65 years and (B) <65 years.
Figure 3.
Figure 3.
Time to deterioration of patient-reported outcomesa by age subgroup. aAssessed using EORTC questionnaire QLQ-C30 and QLQ-H&N35 for pain (composite of items 31–34) and swallowing (composite of items 35–38). CI, confidence interval; EORTC, European Organization for Research and Treatment of Cancer; GHS, global health status; HR, hazard ratio; QLQ-C30, quality-of-life questionnaire C30; QLQ-H&N35, quality-of-life questionnaire head and neck cancer-specific module.
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