LUX-Lung 4 – Afatinib* Phase I Trial in Advanced Non-Small Cell Lung Cancer Patients and Phase II Trial in Non-Small Cell Lung Cancer Patients Failing Erlotinib or Gefitinib

Japanese Phase I/II open-label trial of continuous once daily oral treatment with afatinib – Phase I trial in patient with advanced non-small cell lung cancer (NSCLC) and Phase II trial in patients with NSCLC after failure of erlotinib or gefitinib.

Trial CTgov-Identifier: NCT00711594


Stage IIIB/IV NSCLC of adenocarcinoma histology

Failure of conventional treatment or no therapy of proven efficacy 

Progressed after one or two lines of chemotherapy (including one platinum-based regimen) and ≥12 weeks of treatment with erlotinib or gefitinib (Phase II)

Eastern Cooperative Oncology Group performance status 0–1

N = 74 (N=12 for Phase I, N=62 for Phase II)
  • Phase I: afatinib
    Oral once daily finding maximum tolerated dose up to 50 mg/day

  • Phase II: afatinib
    Oral once daily, continuous treatment at high dose


Phase I primary outcome measures:
Safety of afatinib – incidence of dose limiting toxicity and incidence and intensity of adverse events (AEs)

Phase I secondary outcome measures: 
Pharmacokinetics of afatinib after multiple oral administration 
Summary of epidermal growth factor receptor (EGFR) mutations 

Phase II primary outcome measures: 
Objective response rate

Phase II secondary outcome measures: 
Disease control rate 
Time to and duration of objective response 
Duration of disease control
Progression-free survival (PFS) assessed by independent central review
Overall survival (OS) 
Summary of EGFR mutations


Of 61 patients evaluable for tumour response in the Phase II trial, five had a confirmed objective response to afatinib (8.2%; 95% CI 2.7–18.1%). Tumour size was reduced in 79% of all patients, with nine patients (16%) showing at least a 30% reduction. Median PFS was 4.4 months and median OS was 19.0 months.

Waterfall plot

The most common drug-related AEs were diarrhoea (100%) and rash/acne (91.9%).


Afatinib showed activity in patients with NSCLC who had received third- or fourth-line treatment and who had disease progression while receiving erlotinib and/or gefitinib.


Katakami N, Atagi S, Goto K, et al. LUX-Lung 4: A phase II trial of afatinib in patients with advanced non-small-cell lung cancer who progressed during treatment with erlotinib, gefitinib, or both. J Clin Oncol 2013;31(27):3335–3341. (Accessed: April 2017).