The irreversible ErbB family inhibitor afatinib (Gilotrif) was associated with improvement in progression-free survival and time to treatment failure vs the reversible EGFR (epidermal growth factor receptor) inhibitor gefitinib (Iressa) in the first-line treatment of EGFR-mutant non–small cell lung cancer (NSCLC), according to the LUX-Lung 7 trial reported by Park et al in The Lancet Oncology.
In the open-label trial, 319 patients with stage IIIB or IV disease and a common EGFR mutation from 64 sites in 13 countries were randomly assigned between December 2011 and August 2013 to receive afatinib at 40 mg/d (n = 160) or gefitinib at 250 mg/d (n = 159). The primary endpoints originally were progression-free survival and disease control at 12 months; in March 2013, the protocol was changed to include time to treatment failure and overall survival as primary outcomes.
In the afatinib and gefitinib groups, median age was 63 years in both, 57% and 67% were women, 59% and 55% were Asian and 30% and 34% were white, 66% and 67% were never-smokers, and 95% and 98% had stage IV disease.
Median follow-up was 27.3 months. Median progression-free survival was 11.0 months (95% confidence interval [CI] = 10.6–12.9 months) in the afatinib group vs 10.9 months (95% CI = 9.1–11.5 months) in the gefitinib group (hazard ratio [HR] = 0.73, P = .017). Median time to treatment failure was 13.7 months (95% CI = 11.9–15.0 months) vs 11.5 months (95% CI = 10.1–13.1 months; HR = 0.73, P = .0073). Overall survival data were not mature at the time of analysis.
The most common treatment-related grade 3 or 4 adverse events were diarrhea (13% in the afatinib group vs 1% in the gefitinib group), rash or acne (9% vs 3%), and elevated liver enzymes (0% vs 9%). Serious treatment-related adverse events occurred in 11% vs 4%, and treatment-related adverse events led to discontinuation of treatment in 6% in both groups. Fatal adverse events occurred in 9% vs 6% of patients, with one considered to be related to gefitinib treatment.
The investigators concluded: “Afatinib significantly improved outcomes in treatment-naive patients with EGFR-mutated NSCLC compared with gefitinib, with a manageable tolerability profile. These data are potentially important for clinical decision making in this patient population.”
The study was funded by Boehringer Ingelheim.
Keunchil Park, MD, of Sungkyunkwan University School of Medicine, Seoul, Korea, is the corresponding author of The Lancet Oncology article.
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