LUX-Lung 4 – Afatinib* Phase I Trial in Advanced Non-⁠Small Cell Lung Cancer Patients & 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 advanced non-small cell lung cancer (NSCLC) patients & Phase II trial in NSCLC patients after failure of erlotinib or gefitinib.

Trial CTgov-Identifier: NCT00711594


Pathologically confirmed diagnosis of NSCLC
Failure of conventional treatment or no therapy of proven efficacy
Eastern Cooperative Oncology Group performance status 0–1
Progressed after 1 or 2 lines of chemotherapy (incl. 1 platinum-based regimen) and >12 weeks of treatment with erlotinib or gefitinib (Phase Il)

N = 74
  • 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 & 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
Duration of disease control
Progression-free survival (PFS)
Overall survival (OS)
Summary of EGFR mutations


Of 62 evaluable patients in the Phase II trial, five had a confirmed OR 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: May 2016).