Study Design   |   PFS   |   OS   |   HRQoL   |   Safety


LUX-Lung 3 Clinical Trial

Afatinib compared with chemotherapy for 1st-line treatment in EGFR M+ NSCLC.

Read the original LUX-Lung 3 publication.

Study design

Global, randomised, open-label, Phase III study in patients with advanced lung adenocarcinoma, proven EGFR mutations (N=345) and stable brain metastases, comparing 1st-line afatinib with cisplatin plus pemetrexed chemotherapy. Patients were randomly assigned in a 2:1 fashion to oral afatinib 40 mg once per day (n=230) or intravenous cisplatin 75 mg/m2 and pemetrexed 500 mg/m2 once every 21 days up to a maximum of six cycles (n=115). Treatment continued until investigator-assessed progression or death. The primary endpoint was PFS by independent review. Secondary endpoints included ORR, OS, AEs, and patient-reported outcomes.1,2


Afatinib in 1st-line significantly improved PFS compared with chemotherapy1,3

LUX-Lung 3: PFS in patients with common mutations1

Adapted from Sequist L, et al. 2013.1

  • In the overall population, median PFS was 11.1 months for afatinib compared with 6.9 months with pemetrexed/cisplatin (HR: 0.58; 95% CI: 0.43–0.78; p<0.001)1
  • In Del19 patients, median PFS was 13.8 months for afatinib compared with 5.6 months with pemetrexed/cisplatin (HR: 0.26; 95% CI: 0.17–0.42; p<0.0001)3

OS (pre-planned analyses)

Afatinib in 1st-line demonstrated a median OS of 31.6 months in patients with common mutations4

LUX-Lung 3: OS in patients with common EGFR mutations4

Adapted from Yang JC, et al. 2015.4

Afatinib in 1st-line resulted in a median OS of almost 3 years in patients with a Del19 mutation4

LUX-Lung 3: OS in patients with a Del19 mutation4

Adapted from Yang JC, et al. 2015.4


Afatinib in 1st-line significantly delayed time to deterioration of cough and dyspnea compared with chemotherapy5,6

LUX-Lung 3: median TTD of symptoms5,6

Adapted from Wu YL, et al. 2014.5

Afatinib in 1st-line demonstrated significantly superior HRQoL scores compared with chemotherapy, including physical, role and cognitive functioning6

LUX-Lung 3: global health status and functioning – longitudinal analysis of EORTC QLQ-C30 QoL questionnaire scores6

Adapted from Yang JC, et al. 2013.6


The most common AEs with afatinib were diarrhoea, stomatitis, rash, acne and paronychia.1

Post hoc analysis: dose modification effectively reduced AE incidence and severity, with no effect on treatment efficacy7

LUX-lung 3: incidence and severity of AEs before and after dose modification7

Adapted from Yang JC, et al. 2016.7

There was no significant difference in PFS in patients receiving a dose reduction in the first 6 months compared with those who remained on ≥40 mg.7

  • Median PFS 11.3 vs. 11.0 months (HR:1.25; 95% CI:0.91–1.72; p=0.175)

Average trough plasma concentrations of afatinib were higher in the patient population that subsequently received a reduced dose compared with those that remained on a 40 mg dose, with similar trough plasma concentrations achieved following dose modification.7

You can read more about how afatinib dose modification can be used to manage AEs here.

AE=adverse event, CI=confidence interval, EGFR M+=epidermal growth factor receptor mutation positive, EORTC QLQ-30=European Organisation for Research and Treatment of Cancer 30-question quality of life questionnaire, HR=hazard ratio, HRQoL=health-related quality of life, NSCLC=non-small-cell lung cancer, ORR=objective response rate, OS=overall survival, PFS=progression-free survival, TTD=time to deterioration


Sequist LV, et al. J Clin Oncol 2013;31(27):3327–3334.
Sequist LV, et al. J Clin Oncol 2013;31(27):3327–3334. Supplementary material.
GIOTRIF® (afatinib) Summary of Product Characteristics, 2018.
Yang JC, et al. Lancet Oncol 2015;16(2):141–151.
Wu YL, et al. Updated Analysis of Response and Patient-reported Outcomes (PRO) in Two Large Open-label, Phase III Studies (LUX-Lung 3 [LL3] and LUX-Lung 6 [LL6]) of Afatinib versus Chemotherapy in Patients with Advanced NSCLC Harbouring EGFR Mutations. ESMO. 26–30 September 2014. Madrid, Spain. Poster: 1251P.
Yang JC, et al. J Clin Oncol 2013;31(27):3342–3350.
Yang JC, et al. Ann Oncol 2016;27(11):2103–2110.