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(aEuro)

作者：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 Jr; de Souza Viana L; Keilholz U; del Campo J M; Cong X J; Ehrnrooth E; Vermorken J B

来源：Annals of Oncology, 2016, 27(8): 1585-1593.

DOI：10.1093/annonc/mdw151

• afatinib
• methotrexate
• HNSCC
• second-line
• phase III
• older

In the LUX-Head & Neck 1 study, older age (a parts per thousand yen65 years) did not adversely affect the benefit in patient-reported outcomes and antitumor activity observed with afatinib over methotrexate, which was consistent with findings from the overall population. Safety in older patients was also consistent with the overall population, favoring afatinib in terms of fewer dose reductions and discontinuations.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 a parts per thousand yen65 and < 65 years.
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.
Of 483 randomized patients, 27% (83 afatinib; 45 methotrexate) were aged a parts per thousand yen65 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.
Advancing age (a parts per thousand yen65 years) did not adversely affect clinical outcomes or safety with afatinib versus methotrexate in second-line R/M HNSCC patients.
NCT01345682 (ClinicalTrials.gov).

• 出版日期2016-8