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LUX-Lung 3 clinical trial

Afatinib vs Chemotherapy as First-Line Treatment in Non-Small Cell Lung Cancer With Epidermal Growth Factor Receptor Mutation

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 Argentina, Australia, Belgium, Brazil, Canada, Chile, France, Germany, Hong Kong, Hungary, Ireland, Italy, Japan, South Korean, Malaysia, Peru, Philippines, Romania, Russia, Taiwan, Thailand, Ukraine, the UK and the US.

Trial NCT00949650


Stage IIIB/IV adenocarcinoma of the lung

EGFR mutation positive

No prior treatment with chemotherapy for advanced/metastatic disease

No prior treatment with EGFR inhibitors

Eastern Cooperative Oncology Group (ECOG) performance status of 0–1

Stable brain metastases at baseline permitted



Randomisation 2:1

Afatinib 40 mg Oral once daily
Cisplatin / pemetrexed 75 mg/m² + 500 mg/m² Intravenous, once every 3 weeks for up to 6 cycles


Primary outcome measure:

  • Progression-free survival (PFS) assessed by independent central review


Secondary outcome measures:

  • Overall survival (OS)
  • Objective response rate (ORR)
  • Disease control rate
  • Health-Related quality of life (HRQoL)
  • Pharmacokinetics
  • Safety


PFS by independent review:

In the overall population, median PFS was significantly longer with afatinib at 11.1 months compared with 6.9 months with cisplatin/pemetrexed.

Hazard ratio = 0.58 95% CI = 0.43–0.78
LUX-Lung 3: figure for progression-free survival (PFS) in the overall population


Median PFS among those with common EGFR mutations (del19 and L858R) was 13.6 months for afatinib and 6.9 months for cisplatin/pemetrexed.

LUX-Lung 3: figure for progression-free survival (PFS) in patients with common EGFR mutations


In the overall population, there was no significant OS benefit with afatinib treatment. In a prespecified subgroup analysis of patients with del19 mutation, afatinib demonstrated ≥1 year OS benefit compared with cisplatin/pemetrexed.

Patients with del19 mutations:

LUX-Lung 3: figure for overall survival (OS) in patients with del19 mutations


The most common treatment-related adverse events were:

  • For afatinib:
    • Diarrhoea
    • Rash/acne
    • Stomatitis/mucositis
  • For cisplatin/pemetrexed:
    • Nausea
    • Decreased appetite
    • Fatigue


Afatinib improved global health status and HRQoL, and delayed time to deterioration for cough and dyspnoea, when compared with cisplatin/pemetrexed.


Compared with cisplatin/pemetrexed, afatinib significantly delayed the time to deterioration of cough and dyspnoea. The delayed deterioration time for pain was not statistically significant.

LUX-Lung 3: HRQoL forest plot for time to deterioration in patient symptoms with afatinib vs cis/pem


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

LUX-Lung 3: global health status forest plot for afatinib vs cis/pem


Afatinib significantly prolonged PFS over standard of care chemotherapy. Patients with advanced adenocarcinoma of the lung and EGFR del19 mutation treated with afatinib had a significant OS benefit of more than 1 year compared with cisplatin/pemetrexed chemotherapy.


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Sequist LV, et al. J Clin Oncol 2013;31(27):3327–3334.


Yang JC, et al. J Clin Oncol 2013;31(27):3342–3350.


Yang JC, et al. Lancet Oncol 2015;16(2):141–151.

4 (Accessed: July 2017).

Listen to Prof. Thomas J. Lynch talk about the LUX-Lung 3 results

Prof. Lynch on LUX-Lung 3

Listen to Prof. Thomas J. Lynch talk about the LUX-Lung 3 results

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*Afatinib is approved in more than 80 markets including the EU, Japan, Taiwan, and Canada under the brand name GIOTRIF®, in the US under the brand name GILOTRIF® and in India under the brand name Xovoltib®; for the full list please see here. Registration conditions differ internationally; please refer to locally approved prescribing information.