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.
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
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
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.
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.
Clinicaltrials.gov. https://clinicaltrials.gov/ct2/show/NCT00711594 (Accessed: April 2017).