LUME-Lung 1 – Nintedanib** Plus Docetaxel vs Placebo Plus Docetaxel in Non‑Small Cell Lung Cancer After First‑Line Chemotherapy Failure

Multicentre, randomised, double‑blind, Phase III trial to investigate the efficacy and safety of oral nintedanib plus standard docetaxel therapy compared with placebo plus standard docetaxel therapy in patients with Stage IIIB/IV or recurrent non‑small cell lung cancer (NSCLC) after failure of first‑line chemotherapy.

Trial CTgov-Identifier: NCT00805194


Histologically or cytologically confirmed, locally advanced and/or metastatic NSCLC of Stage IIIB/IV or recurrent NSCLC (all histologies)
Relapse or failure of one first‑line chemotherapy
Eastern Cooperative Oncology Group (ECOG) performance score of 0–1

N = 1314

Randomisation 1:1
Histologies were balanced between treatment arms (adenocarcinoma n=658 (50.1%); squamous cell carcinoma n=555 [42.2%]; other n=101 [7.7%])

  • Nintedanib 200 mg
    Oral twice daily (d2–21, of every 3‑week cycle)
    Standard chemotherapy with docetaxel 75 mg/m2
    Intravenous (IV) once daily (d1, of every 3-week cycle)

  • Placebo 200 mg
    Oral twice daily (d2–21, of every 3‑week cycle)
    Standard chemotherapy with docetaxel 75 mg/m2
    IV once daily (d1, of every 3‑week cycle)


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

Key Secondary Outcome Measure:
Overall survival (OS)

Additional Secondary Outcome Measures: PFS (investigator-assessed)
Objective response rate
Disease control rate
Patient reported outcomes and health‑related‑quality of life Pharmacokinetics


PFS, intent‑to‑treat population (all histologies):

Median PFS was 3.4 months for nintedanib plus docetaxel and 2.7 months for placebo plus docetaxel (HR 0.79; 95% CI 0.68–0.92; p=0.0019) regardless of histology.

PFS: intent-to-treat population (all histologies)


Whilst there was no significant OS difference for the overall patient population, a pre‑specified analysis of OS identified a significant OS benefit beyond 1 year with nintedanib plus docetaxel in patients with adenocarcinoma compared with placebo plus docetaxel.

OS Adenocarcinoma patients

In European patients with adenocarcinoma a 4.7 month improvement in median OS was observed for nintedanib plus docetaxel compared with placebo plus docetaxel (HR 0.79; 95% CI 0.65–0.97; p=0.0254).

The outcome further improved in several populations within the patients with adenocarcinoma, including time to first‑line progression <9 months or progressive disease as best response to first-line therapy.

The most frequent adverse events (AEs) were diarrhoea (grade ≥3, 6.6%), reversible increases in alanine aminotransferase (7.8%) and reversible increases in aspartate aminotransferase (3.4%) for nintedanib plus docetaxel. Overall, there was a slightly greater incidence of AEs at grade ≥3 for nintedanib plus docetaxel compared with placebo plus docetaxel (71.3% vs 64.3%) but withdrawals due to AEs were similar in both arms (22.7% vs 21.7%).


Nintedanib plus docetaxel significantly improved PFS for patients with advanced NSCLC of all histologies, and provided a significant OS benefit for patients with adenocarcinoma beyond 1 year, following progression after initial chemotherapy. These results were mirrored in European patients with adenocarcinoma.

Several populations within the patients with adenocarcinoma have been identified that derive specific benefit from nintedanib plus docetaxel with the benefit getting more pronounced the shorter the time since first-line chemotherapy.


Reck M, Kaiser R, Mellemgaard A, et al. Docetaxel plus nintedanib versus docetaxel plus placebo in patients with previously treated non‑small‑cell lung cancer (LUME‑Lung 1): a phase 3, double‑blind, randomised controlled trial. Lancet Oncol 2014;15(2):143–155.

Heigener D, Gottfried M, Bennouna J, et al. Efficacy and safety of nintedanib (NIN)/docetaxel (DOC) in patients with lung adenocarcinoma: Further analyses from the LUME-Lung 1 study. Ann Oncol 2016;27(Suppl. 6): Abstract 1276P. (Accessed: November 2016).