LUX-Lung 3: A randomized, open-label, phase III study of afatinib versus pemetrexed and cisplatin as first-line treatment for patients with advanced adenocarcinoma of the lung harboring EGFR-activating mutations.

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


J Clin Oncol 30, 2012 (suppl; abstr LBA7500)
James Chih-Hsin Yang, Martin H. Schuler, Nobuyuki Yamamoto, Kenneth John O'Byrne, Vera Hirsh, Tony Mok, Sarayut Lucien Geater, Sergey V Orlov, Chun-Ming Tsai, Michael J. Boyer, Wu-Chou Su, Jaafar Bennouna, Terufumi Kato, Vera Gorbunova, Ki Hyeong Lee, Riyaz N.H. Shah, Dan Massey, Robert M. Lorence, Mehdi Shahidi, Lecia V. Sequist; National Taiwan University Hospital, Taipei, Taiwan; Department of Medical Oncology, West German Cancer Center, Essen, Germany; Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka, Japan; St. James's Hospital, Dublin, Ireland; McGill University - Royal Victoria Hospital, Montreal, QC, Canada; Prince of Wales Hospital, Shatin, Hong Kong; Songklanagarind Hospital, Songkla, Thailand; St. Petersburg Pavlov State Medical University, St. Petersburg, Russia; Taipei Veterans General Hospital, Taipei, Taiwan; Royal Prince Alfred Hospital, Camperdown, Australia; National Cheng Kung University Hospital, Tainan, Taiwan; Centre René Gauducheau, Nantes, France; Kanagawa Cardiovascular and Respiratory Center, Yokohama, Japan; GU Russian Oncological Research Centre, Moscow, Russia; Chungbuk National University Hospital, Daejeon, South Korea; Maidstone and Tunbridge Wells NHS Trust, Maidstone, United Kingdom; Boehringer Ingelheim, Bracknell, United Kingdom; Boehringer Ingelheim, Ridgefield, CT; Massachusetts General Hospital Cancer Center, Boston, MA

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Abstract Disclosures


Background: Afatinib (A) is a selective, orally bioavailable, irreversible ErbB family blocker of EGFR (ErbB1), HER2 (ErbB2), and ErbB4. This global study investigated the efficacy and safety of A compared with pemetrexed/cisplatin (PC) in pts with EGFR mutation positive advanced lung adenocarcinoma. Methods: Following central testing for EGFR mutations (companion diagnostic TheraScreen EGFR RGQ PCR kit), 345 pts (stage IIIB/IV, PS 0–1, chemo-naive) were randomized 2:1 (A: 230; PC: 115) to daily A 40 mg or iv PC (500 mg/m2 + 75 mg/m2 q21 days up to 6 cycles). Primary endpoint was progression-free survival (PFS) by central independent review. Results: Baseline characteristics were balanced in both arms: median age, 61 y; female, 65%; Asian, 72%; never-smoker, 68%; Del19, 49%; L858R, 40%; other mutations, 11%. Treatment with A led to a significantly prolonged PFS vs PC (median 11.1 vs 6.9 mos; HR 0.58 [0.43–0.78]; p=0.0004). In 308 pts with common mutations (Del19/L858R), median PFS was 13.6 vs 6.9 mos, respectively (HR=0.47 [0.34–0.65]; p<0.0001). Objective response rate was significantly higher with A (56% vs 23%; p<0.0001). Significant delay in time to deterioration of cancer-related symptoms of cough (HR=0.60, p=0.0072) and dyspnea (HR=0.68, p=0.0145) was seen with A vs PC. Most common drug-related adverse events (AEs) were diarrhea (95%), rash (62%) and paronychia (57%) with A, and nausea (66%), decreased appetite (53%) and vomiting (42%) with PC. Drug-related AEs led to discontinuation in 8% (A; 1% due to diarrhea) and 12% of pts (PC). Conclusions: LUX-Lung 3 is the largest prospective trial in EGFR mutation positive lung cancer and the first study using pemetrexed/cisplatin as a comparator. Treatment with afatinib significantly prolonged PFS compared to PC, with significant improvements in secondary endpoints. AEs with afatinib were manageable, with a low discontinuation rate. With 4.2 mos PFS improvement in the overall population and 6.7 mos in pts with common mutations, afatinib is a clinically relevant first-line treatment option.