129081-144

Overall survival (OS) in patients (pts) with advanced non-small cell lung cancer (NSCLC) harboring common (Del19/L858R) epidermal growth factor receptor mutations (EGFR mut): Pooled analysis of two large open-label phase III studies (LUX-Lung 3 [LL3] and LUX-Lung 6 [LL6]) comparing afatinib with chemotherapy (CT).

Category: 
Lung Cancer - Non-Small Cell Metastatic
Session Type and Session Title: 
Oral Abstract Session, Lung Cancer - Non-small Cell Metastatic
Abstract Number: 

8004^

Citation: 

J Clin Oncol 32:5s, 2014 (suppl; abstr 8004^)

Author(s): 

James Chih-Hsin Yang, Lecia V. Sequist, Martin H. Schuler, Tony Mok, Nobuyuki Yamamoto, Kenneth John O'Byrne, Vera Hirsh, Sarayut Lucien Geater, Caicun Zhou, Dan Massey, Victoria Zazulina, Yi-Long Wu; National Taiwan University Hospital, Taipei, Taiwan; Massachusetts General Hospital and Harvard Medical School, Boston, MA; Department of Medicine (Cancer Research), West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Essen, Germany; The Chinese University of Hong Kong, Hong Kong, China; Wakayama Medical University, Wakayama, Japan; St. James's Hospital, Dublin, Ireland; McGill University, Montreal, QC, Canada; Prince of Songkla University, Songkhla, Thailand; Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China; Boehringer Ingelheim Ltd, Bracknell, Berkshire, United Kingdom; Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China


Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).

Abstract Disclosures

Abstract: 

Background: Afatinib (A) is an oral, irreversible ErbB family blocker of EGFR, HER2, ErbB3 and ErbB4 signalling. LL3 compared A with cisplatin/pemetrexed in 345 pts recruited globally and LL6 compared A with gemcitabine/cisplatin in 364 Asian pts. The primary analysis (2012) showed improved progression-free survival (PFS) with A versus CT in the overall EGFR mut positive population (HR=0.58 [LL3], HR=0.28 [LL6]) and pts with common (Del19/L858R) EGFR mut (HR=0.47 [LL3], HR=0.25 [LL6]). The FDA has approved A for the first-line treatment of pts with advanced NSCLC harboring common EGFR mut. Here we present a pooled analysis of mature OS data among such pts. Methods: Treatment-naïve pts with EGFR mut stage IIIB/IV NSCLC were randomized 2:1 to 40 mg A or up to 6 cycles of standard CT and stratified by EGFR mut and race (LL3). The primary endpoint was PFS, with OS as a key secondary endpoint. Adverse events were also recorded. Results: The pooled analysis included 631/709 pts randomized into LL3 and LL6 with common EGFR mut (Del19=355, L858R=276); 419 pts received A and 212 received CT. At the time of analysis (January 2014), 404 (64%) pts had died. Median follow-up for OS was 36.5 months. Following progression, 78% of pts received subsequent systemic therapies (median of 3 regimens); 68% in the CT group received EGFR TKIs and 70% in the A group received CT. OS was significantly improved with A versus CT (median 27.3 vs 24.3 months, HR=0.81 [CI 0.66, 0.99; p=0.037]). Individual HRs for OS in LL3 and LL6 were consistent with the pooled analysis. 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 significantly improves OS 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. Clinical trial information: NCT00949650.