LUME-Lung 1 clinical trial

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  recurrent non-small cell lung cancer (NSCLC) after failure of first-line chemotherapy.

Trial CT.gov-Identifier: NCT00805194

Patients

Histologically or cytologically confirmed Stage IIIB/IV recurrent NSCLC (all histologies)

Relapse or failure of one first-line chemotherapy

Eastern Cooperative Oncology Group performance status of 0–1

N=1,314

Randomization 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%])

Endpoints

Primary outcome measure:

• Progression-free survival (PFS) assessed by 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

Results

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 (hazard ratio [HR]=0.79; 95% confidence interval [CI]: 0.68–0.92; p=0.0019) in the overall population.

CI, confidence interval; HR, hazard ratio.

OS: 

OS was analyzed in a prespecified stepwise manner, considering:

• Patients with adenocarcinoma histology whose time since start of first-line therapy (TSFLT) was <9 months
• All patients with adenocarcinoma histology
• All patients

Adenocarcinoma patients with TSFLT <9 months in the nintedanib arm of the study had median OS that was 3 months longer than patients in the placebo arm (10.9 vs 7.9 months; HR=0.75; 95% CI: 0.60‒0.92; p=0.0073). In all patients with adenocarcinoma, OS was also significantly longer in the nintedanib arm than the placebo arm (12.6 vs 10.3 months; HR=0.83; 95% CI: 0.70‒0.99; p=0.0359). In the overall patient population; however, there was no significant difference in OS between the two groups (10.1 vs 9.1 months; HR=0.94; 95% CI: 0.83‒1.05; p=0.2720).

CI, confidence interval; HR, hazard ratio.

CI, confidence interval; HR, hazard ratio.

Safety:

For nintedanib plus docetaxel, the most frequent Grade ≥3 adverse events (AEs) were:

• Diarrhoea (6.6%)
• Reversible increases in alanine aminotransferase (7.8%)
• Reversible increases in aspartate aminotransferase (3.4%)

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%). There was a low incidence of class effects typically associated with antiangiogenic agents, such as hypertension, bleeding, perforation and thromboembolism, and rates were similar for both groups.

Conclusion

Nintedanib plus docetaxel significantly improved PFS for patients with advanced NSCLC of all histologies, and provided a significant OS benefit for patients with adenocarcinoma, extending median OS beyond 1 year, following progression after initial chemotherapy.