Afatinib Improves PFS vs Gefitinib in EGFR-Mutated NSCLC

The ErbB family blocker afatinib resulted in improved progression-free survival (PFS) and other treatment outcomes compared with the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) gefitinib in a randomized, open-label, phase II study of treatment-naive non–small-cell lung cancer (NSCLC) patients with EGFR mutations.

Three drugs-gefitinib, erlotinib, and afatinib-have been shown in separate trials to be superior to first-line platinum-based doublet chemotherapy in EGFR-mutant NSCLC, but previous to this study, no direct comparisons between the drugs had been conducted. “The broad spectrum of activity and irreversible mechanism of action of afatinib has been postulated to be associated with improved inhibition of EGFR-dependent tumor growth compared with first-generation EGFR TKIs,” wrote study authors led by Keunchil Park, MD, of Sungkyunkwan University School of Medicine in Seoul, South Korea.

The new study, dubbed LUX-Lung 7, included 319 patients randomized to either afatinib (160 patients) or gefitinib (159 patients). All patients were EGFR mutation–positive, and the median follow-up period was 27.3 months. The results were published in Lancet Oncology.

The median PFS was 11.0 months with afatinib vs 10.9 months with gefitinib, yielding a hazard ratio (HR) of 0.73 (95% CI, 0.57–0.95; P = .017). The authors noted that the PFS curves separated further over time, beginning at the median. The PFS rate at 24 months was 17.6% with afatinib and 7.6% with gefitinib.

The time-to-treatment failure was also better with afatinib, at 13.7 months vs 11.5 months with gefitinib, for an HR of 0.73 (95% CI, 0.58–0.92; P = .0073). The median overall survival data, the authors noted, were “immature” at the time of the analysis.

More patients treated with afatinib achieved an objective tumor response as well, at 70% compared with 56% with gefitinib, yielding an odds ratio of 1.87 (95% CI, 1.18–2.99; P = .0083).

Almost all patients in both groups experienced some adverse events (AEs); grade 3 or worse AEs occurred in 57% of afatinib and 52% of gefitinib patients. In the afatinib group, serious drug-related AEs occurred in 11%, compared with 4% of gefitinib patients. The most frequent such events in the afatinib patients included diarrhea, rash or acne, and fatigue; in the gefitinib patients, they included increased aspartate transaminase/alanine transaminase concentrations and rash or acne. Dose reductions due to AEs were more common with afatinib (42%) than with gefitinib (2%).

“The improved antitumor activity with afatinib noted in this trial might reflect its more potent and irreversible inhibition of EGFR signaling,” the authors wrote. “Our findings suggest that first-generation and second-generation EGFR targeted drugs might not be interchangeable. We believe that these data provide additional evidence to help to inform decision making when choosing a first-line treatment for patients with EGFR mutation–positive NSCLC.”