Afatinib edges out methotrexate as second-line treatment in Asians with HNSCC

The tyrosine kinase inhibitor (TKI) afatinib confers greater survival benefit than methotrexate in Asian patients with recurrent or metastatic squamous cell carcinoma of the head and neck (HNSCC) when used in the second-line setting, according to the results of the open-label, phase III LUX-Head & Neck 3 trial.

“LUX-Head & Neck 3 … is the second head-to-head trial comparing afatinib and methotrexate in recurrent/metastatic HNSCC following first-line platinum-based therapy,” the investigators said.

“As with LUX-Head & Neck 1, the [current] trial achieved its primary progression-free survival (PFS) endpoint, demonstrating that afatinib is a potential treatment option in this setting. The tolerability profile of [drug] was predictable and manageable,” they added. [Lancet Oncol 2015;16:583-594]

A total of 340 Asian patients, who had disease that recurred or metastasized following first-line platinum-based therapy, were randomized to treatment with oral afatinib (40 mg/day; n=228; median age, 55.5 years) or intravenous methotrexate (40 mg/m²/week; n=112; median age, 58.0 years).

Patients treated with afatinib had significantly better PFS than those who received methotrexate both at week 12 (58 percent vs 41 percent) and week 24 (21 percent vs 9 percent). The TKI cut the risk of progression or death by 37 percent (hazard ratio, 0.63, 95 percent CI, 0.48–0.82; p=0.0005) over a median follow-up of 6.4 months. [Ann Oncol 2019;doi:10.1093/annonc/mdz388]

“Importantly, PFS benefit was generally consistent across prespecified patient subgroups [defined by ECOG performance status and prior estimated glomerular filtration rate (EGFR)-targeted antibody therapy] and over time,” the investigators noted.

PFS improvements occurred in parallel with increases in quality of life. Patients in the afatinib arm showed a greater mean change in global health compared with those in the methotrexate arm (22.9 vs 15.0; difference, 7.9, 3.5–12.4; p=0.0005).

Objective response rate was 28 percent with afatinib and 13 percent with methotrexate. There was no significant between-group difference in overall survival (HR, 0.88, 0.68–1.13; p=0.32).

Median duration of treatment was 91.5 days in the afatinib group and 42.5 days in the methotrexate group. Frequently reported grade ≥3 drug-related adverse events (AEs) were rash/acne (4 percent with afatinib vs 0 percent with methotrexate), diarrhoea (4 percent vs 0 percent), fatigue (1 percent vs 5 percent), anaemia (<1 percent vs 5 percent) and leukopaenia (0 percent vs 5 percent).

Fatal AEs occurred more frequently with afatinib vs methotrexate (23 percent vs 11 percent), although few of these deaths were deemed related to treatment. The investigators explained that the difference observed could reflect the longer duration of exposure to the TKI.

“[Taken together], these results are of particular relevance for patients in Asian countries, where there are high rates of human papillomavirus-negative disease and low rates of EGFR pretreatment. They could also have wider global relevance if immunotherapy agents are approved in the first-line setting, a change that is likely to increase the proportion of second-line patients who are EGFR treatment-naïve,” the investigators said. [Front Oncol 2018;8:310]

“In this regard, further research is needed to evaluate the efficacy of afatinib in the postimmunotherapy setting,” they added.