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. Clément, Thomas Gauler, Jean Pascal Machiels, Robert I. Haddad, J. Fayette, Makoto Tahara, Ezra E W Cohen, D. Cupissol, Juan José Grau, J. Guigay, Francesco Caponigro, Gilberto de Castro, Luciano de Souza Viana, Ulrich Keilholz, José Maria Del Campo, X. J. Cong, Eva Ehrnrooth, J. B. Vermorken

Research output: Contribution to journalArticlepeer-review

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/m2/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).

Original languageEnglish
Pages (from-to)1585-1593
Number of pages9
JournalAnnals of Oncology
Volume27
Issue number8
DOIs
Publication statusPublished - Aug 1 2016

Keywords

  • Afatinib
  • HNSCC
  • Methotrexate
  • Older
  • Phase III
  • Second-line

ASJC Scopus subject areas

  • Medicine(all)
  • Hematology
  • Oncology

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