LUX-Lung 1 – Afatinib* and Best Supportive Care vs Placebo and Best Supportive Care in Non-Small Cell Lung Cancer Patients Failing Erlotinib or Gefitinib

Phase IIb/III, randomised, double-blind trial of afatinib plus best supportive care (BSC) vs placebo plus BSC in patients with non-small cell lung cancer after failure of erlotinib or gefitinib.

Trial CTgov-Identifier: NCT00656136


Stage IIIB/IV adenocarcinoma of the lung
Progressed after one or two lines of chemotherapy (including one platinum-based regimen) and ≥12 weeks of treatment with erlotinib or gefitinib
Eastern Cooperative Oncology Group performance status of 0–2

N = 585

Randomisation 2:1

  • Afatinib 50 mg
    Oral once daily

  • Placebo
    Oral once daily


Primary outcome measures:
Overall survival (OS)

Secondary outcome measures: 
Progression-free survival (PFS) assessed by independent central review
Objective response rate
Duration of response
Health-related quality of life 



Median OS was 10.8 months with afatinib and 12.0 months with placebo; the difference was not statistically significant.

LUX-Lung1 Figure1 OS


Median PFS was longer for afatinib (3.3 months) than for placebo (1.1 months). Twenty-nine patients (7%) had a confirmed objective response to afatinib by independent review, compared with one partial response in the placebo group.

LUX-Lung1 Figure2 PFS

The most common adverse events for afatinib were diarrhoea and rash/acne.


Although there was no benefit in terms of OS, patients on afatinib showed improvement in PFS and response rate relative to placebo, suggesting that afatinib might be of some benefit to patients with advanced lung adenocarcinoma that has progressed after one or two lines of chemotherapy and ≥12 weeks of treatment with either erlotinib and/or gefitinib.


Miller VA, Hirsch V, Cadranel J, et al. Afatinib versus placebo for patients with advanced, metastatic non-small cell lung cancer after failure of erlotinib, gefitinib, or both, and one or two lines of chemotherapy (LUX-Lung 1): a phase 2b/3 randomised trial. Lancet Oncol 2012;13(5):528–538. [Erratum in: Lancet Oncol 2012;13:e186.] (Accessed: April 2017).