Afatinib versus gemcitabine/cisplatin for first-line treatment of Chinese patients with advanced non-small-cell lung cancer harboring EGFR mutations: subgroup analysis of the LUX-Lung 6 trial

Abstract

Yi-Long Wu,1 Chong-Rui Xu,1 Cheng-Ping Hu,2 Jifeng Feng,3 Shun Lu,4 Yunchao Huang,5 Wei Li,6 Mei Hou,7 Jian Hua Shi,8 Angela Märten,9 Jean Fan,10 Barbara Peil,11 Caicun Zhou12 1Guangdong Lung Cancer Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China; 2Department of Pulmonary Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China; 3Department of Internal Medicine, Jiangsu Provincial Tumor Hospital, Nanjing, Jiangsu, China; 4Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China; 5Department of Thoracic Surgery, Yunnan Tumor Hospital (The Third Affiliated Hospital of Kunming Medical University), Kunming, Yunnan, China; 6Department of Hematology & Oncology, Cancer Center, First Hospital of Jilin University, Changchun, Jilin, China; 7Lung Cancer Centre, West China Hospital, Sichuan University, Chengdu, Sichuan, China; 8Department of Oncology, Lin Yi Tumor Hospital, Linyi, Shandong, China; 9Department of Oncology, Boehringer Ingelheim GmbH, Ingelheim, Germany; 10Department of Oncology, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, CT, USA; 11Department of Oncology, Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany; 12Department of Medical Oncology, Shanghai Pulmonary Hospital, Yangpu District, Shanghai, China Introduction: Non-small-cell lung cancer (NSCLC) is the leading cause of cancer death in China. Four epidermal growth factor receptor (EGFR)-targeted tyrosine kinase inhibitors – afatinib, erlotinib, icotinib, and gefitinib – are available for first-line treatment of NSCLC in China; however, there are few data to guide treatment choice. The Phase III LUX-Lung 6 trial compared afatinib with platinum-based chemotherapy for first-line treatment of patients from Southeast Asia with EGFR mutation-positive advanced NSCLC. This post hoc analysis assessed the findings from LUX-Lung 6 in Chinese patients. Clinical trial registration: ClinicalTrials.gov: NCT01121393. Materials and methods: Previously untreated patients with EGFR mutation-positive stage IIIB/IV lung adenocarcinoma were randomized 2:1 to receive afatinib or ≤6 cycles of gemcitabine/cisplatin. The key outcomes were progression-free survival (PFS; primary), objective response rate, disease control rate, overall survival (OS), duration of response and disease control, patient-reported outcomes, and safety. Three hundred and twenty-seven patients from mainland China were treated (89.8% of overall LUX-Lung 6 population; afatinib 217, gemcitabine/cisplatin 110). Results: PFS was significantly longer with afatinib than gemcitabine/cisplatin (median 11.0 versus 5.6 months; hazard ratio [HR], 0.30 [95% CI, 0.21, 0.43]; P<0.0001). Overall, there was no significant difference in OS between treatment arms; however, in a subgroup analysis, afatinib significantly improved OS versus gemcitabine/cisplatin in patients with an EGFR Del19 mutation (median 31.6 versus 16.3 months; HR, 0.61 [95% CI, 0.41, 0.91]; P=0.0146). Afatinib was well tolerated, with most treatment-related adverse events (TRAEs) being of grade 1 or 2 severity. The most common grade 3/4 TRAEs with afatinib were rash/acne (15.9%/0.5%), stomatitis (6.1%/0%), and diarrhea (5.6%/0%). TRAEs leading to permanent discontinuation were reported in 12 patients (5.6%) receiving afatinib and 43 (41.7%) receiving gemcitabine/cisplatin. Afatinib significantly improved PFS compared with standard first-line chemotherapy in Chinese patients with EGFR mutation-positive NSCLC and demonstrated a manageable safety profile. Conclusion: The findings support the rationale for using afatinib as a first-line treatment option for this patient population. Keywords: afatinib, NSCLC, EGFR, first-line, Phase III, Chinese patients

Keywords

• Afatinib
• NSCLC
• EGFR
• first-line
• Phase III
• Chinese patients