Chicago, IL—Data presented at ASCO 2013 from the phase 3 clinical trial, known as LUX-Lung 6, show that Asian patients with epidermal growth factor receptor (EGFR) or ErbB1 mutation–positive advanced non–small-cell lung cancer (NSCLC) who were treated with first-line afatinib (Gilotrif) had a doubling in progression-free survival (PFS) compared with treatment with standard chemotherapy with gemcitabine and cisplatin. A few weeks after the release of the data at the meeting, the US Food and Drug Administration (FDA) approved afatinib for the first-line treatment of patients with nonmetastatic NSCLC and EGFR exon 19 deletions or exon 21 substitution mutations, as detected by a companion diagnostic test approved by the FDA concomitantly with afatinib.
The data were released in a poster presented by Yi-Long Wu, MD, of the Guangdong Lung Cancer Institute, Guangdong General Hospital, Guangzhou, China. Afatinib targets the entire ErbB/HER family of receptors, including EGFR and ErbB1 and ErbB2.
The LUX-Lung 6 study is the largest prospective trial of patients with NSCLC plus EGFR mutations. The study included 664 patients from China, the Republic of Korea, and Thailand with advanced NSCLC and EGFR mutation who were randomized in a 2:1 ratio to first-line treatment with oral afatinib 40 mg daily or to intravenous gemcitabine 75 mg/m2 plus cisplatin 1000 mg/m2 every 21 days for up to 6 cycles.
The median PFS was 11.0 months in patients randomized to afatinib compared with 5.6 months in patients randomized to chemotherapy (hazard ratio [HR], 0.28; P <.001). These PFS findings were consistent across all subgroups. Median PFS results from the investigator review were similar—13.7 months with afatinib versus 5.6 months with chemotherapy (HR, 0.26; P <.001).
Patients in the afatinib arm also had a significantly higher objective response rate compared with those receiving chemotherapy (66.9% vs 23.0%, respectively; P <.001) and a significantly higher disease control rate (92.6% vs 76.2%; P <.001). Approximately 47% of patients receiving afatinib are currently alive and progression free after 1 year of treatment compared with 2% of the patients who received chemotherapy.
The safety profile was as expected in both treatment arms, and consistent with previous studies, according to Dr Wu. The most common grade 3 adverse events (AEs) associated with afatinib were EGFR-mediated events (ie, diarrhea, rash, and stomatitis/mucositis). Nausea and vomiting, bone marrow suppression, and fatigue were more frequent with chemotherapy.
The discontinuation rate resulting from AEs was 5.9% with afatinib and 39.8% with chemotherapy.
Patient-reported outcomes were evaluated as secondary end points of LUX-Lung 6. “Significantly more patients had symptom improvement with afatinib for the prespecified symptoms of cough [P = .003], dyspnea [P <.001], and pain [P = .003],” said Dr Wu.
Health-related quality of life (QOL) was measured using the European Organisation for Research and Treatment of Cancer QLQ-C30 questionnaire, which evaluated global health status/QOL (ie, overall well-being) in addition to physical, cognitive, role, social, and emotional functioning. Based on a review of these 6 measurements, afatinib-treated patients had improvements in global health–related QOL and physical, role, and social functioning compared with chemotherapy (P <.05).