LUX-Lung 3 – Afatinib* vs Chemotherapy as First-⁠Line Treatment in Non-⁠Small Cell Lung Cancer With Epidermal Growth Factor Receptor Mutation

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.

Trial CTgov-Identifier: NCT00949650


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

N = 345

Randomisation 2:1

  • 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
Health-Related Quality of Life (HRQoL)


PFS assessed by independent review:

Median PFS was 11.1 months for afatinib and 6.9 months for cisplatin/pemetrexed.

PFS All randomised patients

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.

PFS Patients with common mutations

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.

Prespecified LUX-Lung 3 analysis

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 LUX-Lung 3 and LUX-Lung 6 trials demonstrated clinical activity of afatinib in patients with EGFR mutation positive non-small cell lung cancer and asymptomatic brain metastases.

PFS and ORR in patients with brain metastases

ORR in patients with and without brain metastases

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 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.

Schuler M, Wu YL, Hirsh V et al. First-Line Afatinib versus Chemotherapy in Patients with Non-Small Cell Lung Cancer and Common Epidermal Growth Factor Receptor Gene Mutations and Brain Metastases. J Thorac Oncol 2016;11(3):380-390.