RESULTS REPORTED

LUX-Lung 6 – Afatinib* vs Cisplatin + Gemcitabine in Asian Patients with Epidermal Growth Factor Receptor Mutation-⁠positive Advanced Non-⁠small Cell Lung Cancer

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: NCT01121393

Patients:

Adenocarcinoma of the lung
EGFR mutation positive
Stage IlIB/IV
No prior treatment with chemotherapy for advanced/metastatic disease
No prior treatment with EGFR inhibitors
Eastern Cooperative Oncology Group performance status 0–1

N = 364

Randomisation 2:1

  • Afatinib 40 mg
    Oral once daily

  • Cisplatin + Gemcitabine
    75 mg/m² + 1000 mg/m² Intravenous d1+d8, once every 3 weeks up to 6 cycles

Endpoints:

Primary Outcome Measures:
Progression-free survival (PFS), assessed by an independent central radiology review

Secondary Outcome Measures:
Objective response rate
Disease control rate
Overall survival (OS)
Time to and duration of objective response
Duration of disease control
Health-related quality of life (HRQoL)
Pharmacokinetics

Results:

PFS:
In the intent-to-treat population, median PFS was 11.0 months for afatinib and 5.6 months for cisplatin/gemcitabine.

PFS All randomised patients

OS:
In a pre-specified OS analysis by mutation subgroups, patients with del19 mutation treated with afatinib demonstrated ≥1 year OS benefit compared with del19 mutation patients treated with cisplatin/gemcitabine.

Analysis of patients with del19 mutation

In the overall patient population, there was no significant OS (secondary endpoint) benefit of afatinib compared with cisplatin/gemcitabine with a median OS of 23.1 months in the afatinib group compared with 23.5 months in the cisplatin/gemcitabine group (p=0.61).

HRQoL:

Compared with cisplatin/gemcitabine, afatinib showed better control of cancer-related dyspnoea, cough and pain.

Time to Deterioration

The most common treatment-related adverse events were diarrhoea, rash/acne and stomatitis/mucositis for afatinib, and vomiting, nausea and neutropenia for cisplatin/gemcitabine.

Afatinib also showed significant improvements in Global Health Status (as an indicator of overall HRQoL).

Mean Treatment Difference

Conclusion:

First-line afatinib for treatment of patients with advanced adenocarcinoma significantly (p<0.0001) improved PFS, vs treatment with cisplatin/gemcitabine chemotherapy. In addition, patients with EGFR del19 mutation showed >1 year overall survival.

Afatinib showed improved efficacy and clinical benefit compared with cisplatin/gemcitabine chemotherapy in patients with previously untreated advanced adenocarcinoma of the lung and EGFR mutations. Afatinib was also associated with better control of lung cancer-related symptoms and improvement in HRQoL.

References:

Wu YL, Zhou C, Hu CP, et al. Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer harbouring EGFR mutations (LUX-Lung 6): an open-label, randomized phase 3 trial. Lancet Oncol 2014;15(2):213-222.

Geater SL, Xu CR, Zhou C, et al. Symptom and Quality of Life Improvement in LUX-Lung 6: An Open-Label Phase III Study of Afatinib Versus Cisplatin/Gemcitabine in Asian Patients With EGFR Mutation-Positive Advanced Non-small-cell Lung Cancer. J Thorac Oncol. 2005 Jun;10(6):883-889.

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.

Clinicaltrials.gov. https://clinicaltrials.gov/ct2/show/study/NCT01121393 (Accessed: May 16).

X