A randomised, open-label, Phase III study of afatinib vs chemotherapy as first-line treatment for patients with Stage IIIB or IV adenocarcinoma of the lung harbouring an epidermal growth factor receptor (EGFR) activating mutation. Patients were recruited at centres in Argentina, Australia, Belgium, Brazil, Canada, Chile, France, Germany, Hong Kong, Hungary, Ireland, Italy, Japan, South Korean, Malaysia, Peru, Philippines, Romania, Russia, Taiwan, Thailand, Ukraine, the UK and the US.
LUX-Lung 3 – Afatinib* vs Chemotherapy as First-Line Treatment in Non-Small Cell Lung Cancer With Epidermal Growth Factor Receptor Mutation
Stage IIIB/IV adenocarcinoma of the lung
EGFR mutation positive
No prior treatment with chemotherapy for advanced/metastatic disease
No prior treatment with EGFR inhibitors
Eastern Cooperative Oncology Group (ECOG) performance status of 0–1
Afatinib* 40 mg
Oral once daily
75 mg/m² + 500 mg/m²
Intravenous, once every 3 weeks for up to 6 cycles
Primary outcome measures:
Progression-free survival (PFS), assessed by independent central review
Secondary outcome measures:
Overall survival (OS)
Objective response rate (ORR)
Disease control rate
Health-Related quality of life (HRQoL)
In the overall population, median PFS was significantly longer with afatinib at 11.1 months compared with 6.9 months with cisplatin/pemetrexed.
Median PFS among those with del19 and L858R EGFR mutations was 13.6 months for afatinib and 6.9 months for cisplatin/pemetrexed.OS:
In the overall population, there was no significant OS benefit with afatinib treatment. In a prespecified subgroup analysis of patients with del19 mutation, afatinib demonstrated ≥1 year OS benefit compared with cisplatin/pemetrexed.Safety:
The most common treatment-related adverse events were diarrhoea, rash/acne, and stomatitis/mucositis for afatinib and nausea, decreased appetite, and fatigue for cisplatin/pemetrexed. Compared with cisplatin/pemetrexed, afatinib improved global health status and HRQoL, and delayed time to deterioration for cough and dyspnoea.HRQoL
Compared with cisplatin/pemetrexed, afatinib significantly delayed the time to deterioration of cough and dyspnoea. The delayed deterioration time for pain was not statistically significant.
Afatinib significantly prolonged PFS over standard of care chemotherapy. Patients with advanced adenocarcinoma of the lung and EGFR del19 mutation treated with afatinib had a significant OS benefit of more than 1 year compared with cisplatin/pemetrexed chemotherapy.
Sequist LV, Yang JC, Yamamoto N, et al. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol 2013;31(27):3327–3334.
Yang JC, Hirsh V, Schuler M, et al. Symptom control and quality of life in LUX-Lung 3: A phase III study of afatinib or cisplatin/pemetrexed in patients with advanced lung adenocarcinoma with EGFR mutations. J Clin Oncol 2013;31(27):3342–3350.
Yang JC, Wu YL, Schuler M, et al. Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX Lung 3 and LUX Lung 6): analysis of overall survival data from two randomised, phase 3 trials. Lancet Oncol 2015;16(2):141–151.
Clinicaltrials.gov. https://clinicaltrials.gov/ct2/show/NCT00949650 (Accessed: April 2017).