Clement, P. M.Gauler, T.Machiels, J. P.Haddad, R. I.Fayette, J.Licitra, L. F.Tahara, M.Cohen, E. E. W.Cupissol, D.Grau, J. J.Guigay, J.Caponigro, F.de Castro, G.de Souza Viana, L.Keilholz, U.del Campo, J. M.Cong, X. J.Ehrnrooth, E.Vermorken, J. B.2016-08-092016Clement, P. M., T. Gauler, J. P. Machiels, R. I. Haddad, J. Fayette, L. F. Licitra, M. Tahara, et al. 2016. “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†.” Annals of Oncology 27 (8): 1585-1593. doi:10.1093/annonc/mdw151. http://dx.doi.org/10.1093/annonc/mdw151.0923-7534http://nrs.harvard.edu/urn-3:HUL.InstRepos:27822217Background: 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).en-USafatinibmethotrexateHNSCCsecond-linephase IIIolderJournal Article2016-08-0910.1093/annonc/mdw151