Study Design   |   PFS   |   OS   |   Safety

 

LUX-Lung 6 Clinical Trial

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

Read the original LUX-Lung 6 publication.


Study design

Randomised, open-label, Phase III study at 36 centres in China, Thailand, and South Korea, comparing 1st-line afatinib with gemcitabine and cisplatin in Asian patients with EGFR M+ advanced NSCLC (N=364). Patients were randomly assigned (2:1) to receive either oral afatinib 40 mg once per day (n=242) or intravenous gemcitabine 1000 mg/m² on Day 1 and Day 8 plus cisplatin 75 mg/m² on day 1 of a 3-week schedule for up to six cycles (n=122). Patients with stable brain metastases were permitted in the trial. The primary endpoint was PFS by independent review or death. Secondary endpoints included ORR, OS, duration of response, AEs, and patient-reported outcomes.1,2


PFS

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

LUX-Lung 6: PFS in whole population1

LUX-Lung 6 study results: chart showing PFS in whole population

Adapted from Wu YL, et al. 2014.1


OS (pre-planned analysis)

Afatinib in 1st-line provided >1 year median OS improvement in patients with Del19 mutations compared with chemotherapy2

LUX-Lung 6: OS in patients with a Del19 mutation (pre-planned subgroup analysis)2

LUX-Lung 6 study results: chart showing OS in patients with a Del19 mutation

Adapted from Yang JC, et al. 2015.2


Safety

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

Post hoc analysis: dose modification effectively reduced AE incidence and severity, with no effect on treatment efficacy3

LUX-Lung 6: incidence and severity of AEs before and after dose modification

LUX-Lung 6 study results: chart with incidence and severity of AEs before and after dose modification

Adapted from Yang JC, et al. 2016.3

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.3

  • Median PFS 12.3 vs. 11.0 months (HR=1.00; 95% CI:0.69–1.46; p=0.982)

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.3

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


AE=adverse events, CI=confidence interval, EGFR M+=epidermal growth factor receptor mutation positive, HR=hazard ratio, NSCLC= non-small-cell lung cancer, OS=overall survival, PFS=progression-free survival, TTF=time-to-treatment failure

aA grouped term


References

1
Wu YL, et al. Lancet Oncol 2014;15(2):213–222.
2
Yang JC, et al. Lancet Oncol 2015;16(2):141–151.
3
Yang JC, et al. Ann Oncol 2016;27(11):2103–2110.