Recurrent and metastatic head and neck squamous-cell carcinoma (SCC) is associated with a poor prognosis, and the treatment options are limited in this disease setting, highlighting the need for novel treatment strategies. Afatinib is an irreversible inhibitor of the ErbB family that has demonstrated antitumor activity in early clinical trials in this setting. The LUX-Head and Neck 1 study is a phase 3 clinical trial that evaluated second-line afatinib (40 mg/day) versus methotrexate monotherapy in 483 patients with recurrent and metastatic head and neck SCC after disease progression while receiving platinum-based therapy (Machiels J-P, et al. LUX-Head & Neck 1. ESMO 2014: Abstract LBA29). The primary end point was progression-free survival (PFS); secondary end points were overall survival (OS) and objective response rate (ORR).
The efficacy analysis showed that afatinib monotherapy (n = 322) led to a significant improvement in PFS (median, 2.6 vs 1.7 months; hazard ratio [HR], 0.80; P = .03) compared with methotrexate (n = 161). The 3-month PFS rates were 42.8% and 30.5% in the afatinib and methotrexate cohorts, respectively; however, the PFS advantage did not translate into a significant improvement in OS (6.8 vs 6.2 months; HR, 0.94).
Afatinib-treated patients achieved a significantly higher disease control rate compared with patients receiving methotrexate (49.1% vs 38.5%; P = .04); the ORR was numerically higher, but did not reach statistical significance (10.2% vs 5.6%; P = .10). In addition, tumor shrinkage from baseline was observed in 34.8% of afatinib-treated patients compared with 22.4% of patients treated with methotrexate. In terms of treatment effect on quality of life (QOL), afatinib significantly delayed the deterioration of global health status, pain, and swallowing compared with methotrexate (all P ?.03).
The safety analysis showed that common grade 3 or 4 afatinib-related adverse events were rash/acne (9.7%) and diarrhea (9.4%), whereas methotrexate-related adverse events included leukopenia (15.6%) and stomatitis (8.1%). Treatment-related dose reductions and treatment discontinuations were lower in patients receiving afatinib.
Overall, these results show that second-line afatinib therapy results in significant, albeit modest, improvements in PFS and QOL, and has a manageable safety profile in patients with recurrent and metastatic head and neck SCC after failing platinum-based therapy.
