LUME-Lung 2 – Nintedanib** Plus Pemetrexed Compared to Placebo Plus Pemetrexed in Non‑Squamous Non‑Small Cell Lung Cancer After First‑Line Therapy Failure

A randomised, double‑blind, multicentre, Phase III trial of nintedanib plus pemetrexed vs placebo plus pemetrexed in patient with advanced or recurrent non‑small cell lung cancer (NSCLC) patients after failure of first‑line therapy

Trial CTgov-Identifier: NCT00806819


Histologically or cytologically confirmed stage IIIB/IV or recurrent NSCLC
Relapse or failure of one first‑line chemotherapy
Eastern Cooperative Oncology Groups (ECOG) performance score of 0‑1

N = 713

Randomisation 1:1

  • Nintedanib* 200 mg
    Oral twice daily (d2‑21 in 3‑week cycles)
    Standard chemotherapy with pemetrexed 500 mg/m2
    Intravenous (IV) (d1 in 3‑week cycles)

  • Placebo 200 mg
    Oral twice daily (d2‑21 in 3‑week cycles)
    Standard chemotherapy with pemetrexed 500 mg/m2
    IV (d1 in 3‑week cycles)


Primary Outcome Measures:
Progression‑free survival (PFS)

Key Secondary Outcome Measure:
Overall survival (OS)


The LUME-Lung 2 trial was stopped early due to futility at a pre‑specified interim analysis based on the investigator‑assessed PFS only. Subsequent analysis of the available intention‑to‑treat population using independently reviewed data showed a PFS benefit for patients treated with nintedanib plus pemetrexed compared with placebo plus pemetrexed (4.4 vs 3.6 months; HR 0.83, 95% CI 0.70‑0.99, p=0.0435), but no difference in OS between the two treatment arms.

The frequency of serious adverse events (AEs) and grade 5 AEs were comparable between the two treatment groups. A similar incidence of grade ≥3 hypertension, bleeding, thrombosis, mucositis and neuropathy was observed in both treatment groups. In patients treated with nintedanib plus pemetrexed there was a higher frequency of grade ≥3 elevated alanine transaminase (23% vs 7%), elevated asparate transaminase (12% vs 2%) and diarrhoea (3% vs 1%) compared with patients treated with placebo plus pemetrexed.


The primary endpoint was met even though the study was stopped early, indicating that nintedanib plus pemetrexed significantly improved PFS (p=0.04) in patients with advanced non‑squamous NSCLC who had progressed on first‑line chemotherapy.


Hanna NH, Kaiser R, Sullivan RN, et al. LUME-Lung 2: A multicenter, randomised, double‑blind, phase III study of nintedanib plus pemetrexed versus placebo plus pemetrexed in patients with advanced non‑squamous non‑small cell lung cancer (NSCLC) after failure of first‑line chemotherapy. J Clin Oncol 2013;31(suppl):Abstract 8034.
(Accessed: May 2016).