Abstract
Background: Afatinib (A) is an oral, irreversible ErbB family blocker of EGFR, HER2, ErbB3 and ErbB4 signalling. A was compared with cisplatin/pemetrexed (LL3; 345 pts recruited globally) and gemcitabine/cisplatin (LL6; 364 Asian pts) in treatment-naïve pts with EGFR mut stage IIIB/IV NSCLC. A improved progression-free survival (PFS) vs CT in pts with common (Del19/L858R) EGFR mut. Here we present a pooled analysis of mature OS data among such pts.
Methods: This analysis included 631/709 pts harboring common EGFR mut (Del19=355, L858R=276) randomized 2:1 to 40 mg A (n=419) or up to 6 cycles of standard CT (n=212).
Results: Median follow-up for OS was 36.5 mo and 404 (64%) pts had died at the time of analysis (January 2014). 78% of pts received subsequent systemic therapies (median of 3 regimens); 68% in the CT group received EGFR tyrosine kinase inhibitors and 70% in the A group received CT. OS was significantly improved with A vs CT (median 27.3 vs 24.3 mo, HR=0.81 [CI 0.66, 0.99; p=0.037]). Among Del19 pts the HR=0.59 (CI 0.45, 0.77; p<0.001) and in L858R pts the HR=1.25 (CI 0.92, 1.71; p=0.160). Updated PFS and safety findings were consistent with earlier primary reports.
Conclusions: This pooled analysis reveals that first-line A improves OS by 3 mo in pts with advanced NSCLC harboring common EGFR mut (Del19/L858R) compared with CT. This is the first analysis to show that genotype-directed therapy for EGFR mut pts can improve survival.
- © 2014 ERS