RESULTS REPORTED

LUX-Lung 6 – Afatinib* vs Cisplatin + Gemcitabine in 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. Patients were recruited at centres in China, Thailand and South Korea.

Trial CTgov-Identifier: NCT01121393

Patients:

Stage IIIB/IV adenocarcinoma of the lung that is EGFR mutation-positive

No prior treatment with chemotherapy for advanced/metastatic disease

No prior treatment with EGFR inhibitors

Eastern Cooperative Oncology Group performance status of 0–1

N = 364

Randomisation 2:1

  • Afatinib 40 mg
    Oral once daily

  • Cisplatin /gemcitabine
    75 mg/m² + 1000 mg/m² Intravenous (Days 1 and 8, once every 3 weeks for up to six cycles)

Endpoints:

Primary outcome measures:
Progression-free survival (PFS) assessed by independent central review 

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

Results:

PFS by independent review:
In the overall population, median PFS was 11.0 months for afatinib and 5.6 months for cisplatin/gemcitabine (Cis/Gem).

PFS All randomised patients

OS:
In the overall population, there was no significant OS benefit with afatinib treatment. In a prespecified 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.

Safety:

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

HRQoL:

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

Afatinib also showed significant improvements in global health status (as an indicator of overall HRQoL).

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 OS benefit.

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. 2015;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/NCT01121393 (Accessed: April 2017).

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