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.
LUX-Lung 3 – Afatinib* vs Chemotherapy as First-Line Treatment in Non-Small Cell Lung Cancer With Epidermal Growth Factor Receptor Mutation
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 performance status (ECOG PS) 0–1
Afatinib* 40 mg
Oral once daily
Cisplatin + Pemetrexed
75 mg/m² + 500 mg/m² iv
Once every 3 weeks, up to 6 cycles
Primary Outcome Measures:
Progression free survival (PFS), assessed by an independent central radiology review
Secondary Outcome Measures:
Overall Survival (OS)
Objective Response rate (ORR)
ECOG PS change since baseline
Disease control rate
Median PFS was 11.1 months for afatinib and 6.9 months for cisplatin/pemetrexed.
Median PFS among those with exon 19 deletions and L858R EGFR mutations was 13.6 months for afatinib and 6.9 months for cisplatin/pemetrexed.
OS in del19 mutation:
In a pre-specified subgroup analysis of patients with del19 mutation, afatinib demonstrated ≥1 year OS benefit compared with pemetrexed/cisplatin.
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.
PFS and ORR in patients with brain metastases:
A post-hoc, exploratory analysis of clinical outcomes combining individual patient data from
ORR in patients with and without brain metastases
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
Yang JC, Hirsh V, Schuler M, et al. Symptom control and quality of life in
Yang JC, Wu YL, Schuler M, et al. Afatinib versus
Schuler M, Wu YL, Hirsh V et al.