Afatinib, Gefitinib Offer Similar OS in EGFR-Mutated NSCLC

The LUX-Lung 7 trial found no significant differences between afatinib and gefitinib for patients with EGFR mutation–positive stage IIIb/IV non–small-cell lung cancer (NSCLC). Afatinib did, however, improve progression-free survival (PFS) and other clinical outcomes.

“NSCLCs with activating EGFR mutations are extremely sensitive to the EGFR-targeting tyrosine kinase inhibitors [TKIs] gefitinib, erlotinib, and afatinib,” wrote study authors led by Luis Paz-Ares, MD, PhD, of Hospital Universitario Doce de Octubre in Madrid. Though the three agents are established as first-line options, there have been limited data comparing them head-to-head.

PFS results of the LUX-Lung 7 trial comparing afatinib and gefitinib were published in 2016, showing a significant improvement with afatinib. The new paper updates those results and adds overall survival (OS) outcomes. The study included 319 patients (160 afatinib, 159 gefitinib), and the results were published in Annals of Oncology.

A total of 109 afatinib patients and 117 gefitinib patients had died as of April 2016; the median treatment duration was 13.7 months and 11.5 months, respectively, and 8.8% and 5.0%, respectively, remained on treatment at data cutoff.

After a median follow-up of 42.6 months, there was no difference with regard to median OS. For afatinib, median OS was 27.9 months, compared with 24.5 months with gefitinib, for a hazard ratio (HR) of 0.86 (95% CI, 0.66–1.12; P = .2580).

This was consistent across prespecified subgroups. The median OS with afatinib in patients with exon 19 deletions was 30.7 months, compared with 26.4 months with gefitinib, for an HR of 0.83 (95% CI, 0.58–1.17; P = .2841). In patients with L858R mutations, the median OS was 25.0 months with afatinib and 21.2 months with gefitinib, for an HR of 0.91 (95% CI, 0.62–1.36; P = .6585). An updated PFS analysis showed similar results to the initial analysis, in favor of afatinib.

The safety analysis was also unchanged, with treatment-related grade 3 or higher adverse events occurring in 31.3% of afatinib patients and in 19.5% of gefitinib patients. Among the most common grade 3 or higher adverse events were diarrhea (13.1%, afatinib; 1.3%, gefitinib), rash/acne (9.4% and 3.1%, respectively), and fatigue (5.6% and 0%, respectively).

“In both treatment arms, survival rates were striking in patients who received a subsequent third-generation EGFR TKI, with 3-year OS rates of up to 90%,” the authors wrote; third-generation TKIs included osimertinib and olmutinib. “These findings bode well for the strategy of sequential treatment with EGFR TKIs, which could potentially make EGFR mutation–positive NSCLC a chronic disease, at least in a subset of patients.”