Afatinib (Gilotrif) Improves Clinical Outcomes Compared With Gefitinib (Iressa) in Head-to-Head Lung Cancer Trial

Treatment reduces risk of disease progression

A global head-to-head phase 2b study has compared afatinib (Gilotrif, Boehringer Ingelheim) and gefitinib (Iressa, AstraZeneca) in patients with non–small-cell lung cancer (NSCLC) whose tumors harbored the most common epidermal growth factor receptor (EGFR) mutations. The results, published in Lancet Oncology, showed that afatinib significantly reduced the risk of lung cancer progression by 27% compared with gefitinib. After two years of treatment, more than twice as many patients treated with afatinib were alive and progression-free compared with those treated with gefitinib (18% vs. 8%, respectively).

Further, patients receiving afatinib had a significantly longer time on treatment, and the risk of treatment failure was reduced by 27%, compared with gefitinib. Significantly more patients had an overall response rate (ORR; a clinically meaningful reduction in tumor size) with afatinib compared with gefitinib (70% vs. 56%), with a median duration of response of 10.1 months versus 8.4 months, respectively. 

Both afatinib and gefitinib demonstrated similar improvements in patient-reported outcome measures, with no significant differences in health-related quality of life. Treatment with either afatinib or gefitinib was generally well tolerated, leading to equal rates of treatment-related discontinuation (6%) in both arms.

The overall rates of adverse events (AEs) were 44% for afatinib and 37% for gefitinib. The most common AEs (grade 3 or greater) with afatinib included diarrhea (13%) and rash/acne (9%), and the most common AEs with gefitinib included increased aspartate aminotransferase (AST)/alanine aminotransferase (ALT) (9%) and rash/acne (3%). Drug-related interstitial lung disease occurred in four patients receiving gefitinib and in no patients receiving afatinib.

The LUX-Lung 7 trial was the first global, head-to-head study comparing second- and first-generation EGFR-directed therapies (afatinib and gefitinib, respectively) in patients with EGFR mutation-positive NSCLC who had received no prior treatments. The study included 319 patients with advanced NSCLC harboring common EGFR mutations (del19 or L858R). The trial’s coprimary endpoints were progression-free survival (PFS), the time to treatment failure, and overall survival (OS); and the secondary endpoints included ORR, the disease control rate, tumor shrinkage, patient-reported outcomes, and safety.

Compared with gefitinib, afatinib significantly improved PFS (hazard ratio [HR], 0.73; P = 0.0165; median: 11.0 months [afatinib] vs. 10.9 months [gefitinib]); the time to treatment failure (HR, 0.73; P =0.0073; median: 13.7 months [afatinib] vs. 11.5 months [gefitinib]); and ORR (70% vs. 56%, P = 0.0083)

Afatinib is indicated for the first-line treatment of patients with NSCLC whose tumors have EGFR exon 19 deletions or exon 21 (L858R) substitution mutations, as detected by an FDA-approved test.

Source: Boehringer Ingelheim; April 13, 2016.