438P - Efficacy of nintedanib/docetaxel in East Asian patients with lung adenocarcinoma (ADE): analysis from the LUME-Lung 1 study

Date 20 December 2015
Event ESMO Asia 2015 Congress
Session Poster presentation 2
Topics Anti-Cancer Agents & Biologic Therapy
Non-Small-Cell Lung Cancer, Metastatic
Presenter Yi-Long Wu
Citation Annals of Oncology (2015) 26 (suppl_9): 125-147. 10.1093/annonc/mdv532
Authors Y. Wu1, Y. Cheng2, B.S. Kim3, S. Lu4, B. Gaschler-Markefski5, R. Kaiser6, M. Reck7
  • 1Guangdong Lung Cancer Institute, Guangdong General Hospital, 510080 - Guangzhou/CN
  • 2Division Of Thoracic Oncology, Jilin Province Cancer Hospital, Changchun/CN
  • 3Department Of Haematology And Oncology, Department Of Internal Medicine, VHS Medical Center, Seoul/KR
  • 4Shanghai Chest Hospital, Shanghai Lung Cancer Center, Shanghai/CN
  • 5Biometrics & Data Management, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach/DE
  • 6Medicine Ta Oncology, Boehringer Ingelheim Pharma GmbH & Co. KG, 88397 - Biberach/DE
  • 7Department Of Thoracic Oncology, Lung Clinic Grosshansdorf, Airway Research Center North (ARCN), Member of the German Center for Lung Research (DZL), 22927 - Grosshansdorf/DE

Abstract

Aim/Background

In the Phase III LUME-Lung 1 study (LL1; NCT00805194; 1199.13), nintedanib (N; Vargatef®) + docetaxel (D) showed significant improvement in the key secondary endpoint overall survival (OS) in ADE patients compared to placebo (P) + D after 1st-line chemotherapy. Time since start of first-line therapy (TSFLT) was identified as a prognostic and predictive clinical marker for survival benefit with N + D in ADE patients (TSFLT <9 months: median OS 10.9 vs 7.9 months; HR 0.75 [95% CI 0.60–0.92], p = 0.0073). Here, we report findings from efficacy analyses in East Asian patients.

Methods

Subgroup analyses in LL1 included the stratification baseline parameters ECOG PS, brain metastases and prior bevacizumab. Analyses of progression-free survival (PFS) and OS were conducted in East Asian patients with ADE (n = 123) (1) stratified by TSFLT 25th percentile (Q1; th percentile (Q3; ≤Q3 vs >Q3) and (2) excluding patients with TSFLT >Q3 or

Results

Compared to the total ADE population, mean and median TSFLT were numerically shorter in East Asian ADE patients (table) and were not balanced between treatment groups, with longer mean (8.4 vs 6.6 months) and median TSFLT (7.4 vs 6.1 months) in the P + D arm versus the N + D arm. Overall, there was no significant interaction for the treatment effect between East Asian vs non-East Asian ethnicity (p = 0.3962 PFS; p = 0.3342 OS). When correcting for the imbalances in TSFLT between the arms, the treatment effect of N in East Asian ADE patients was comparable with that in the entire ADE study population for both PFS and OS. Hazard ratios for PFS and OS in both analyses were below 1, favouring nintedanib. Results were similar in Chinese ADE patients (n = 116).

Conclusions

N + D is an effective treatment option in East Asian ADE patients with locally advanced, metastatic or locally recurrent non-small cell lung cancer after 1st-line chemotherapy.

All adenocarcinoma patients (n = 658) East Asian adenocarcinoma patients (n = 123)
All patients (n = 123) Excluding patients with TSFLT above the 75th percentile (Q3) or below the 25th percentile (Q1) (TSFLT Q1–Q3)
P + D (n = 336) N + D (n = 322) P + D (n = 67) N + D (n = 56) P + D (n = 30) N + D (n = 33)
Mean (standard deviation) TSFLT, months 9.6 (8.9) 9.2 (9.1) 8.4 (5.8) 6.6 (4.3) 6.4 (1.6) 6.7 (1.32)
Median (Q1, Q3) TSFLT, months 7.5 (4.5, 11.9) 7.4 (4.7, 11.1) 7.4 (3.9, 10.7) 6.1 (3.5, 8.0) 6.3 (5.2, 7.7) 6.6 (5.7, 7.8)
Patients with PFS event, n (%) 267 (79.5) 255 (79.2) 54 (80.6) 41 (73.2) 23 (76.7) 22 (66.7)
PFS HR (95% CI) for nintedanib vs placebo stratified by baseline parametersa 0.84 (0.71, 1.00) 1.09 (0.71, 166) 0.57 (0.30, 1.09)
PFS HR (95% CI) for nintedanib vs placebo stratified by TSFLTb 0.83 (0.70, 0.99) 0.74 (0.47, 1.15) Not applicable
Patients with OS event, n (%) 276 (82.1) 259 (80.4) 54 (80.6) 43 (76.8) 25 (83.3) 25 (75.8)
OS HR (95% CI) for nintedanib vs placebo by baseline parametersa 0.83 (0.70, 0.99) 0.93 (0.62, 1.39) 0.72 (0.41, 1.29)
OS HR (95% CI) for nintedanib vs placebo by TSFLTb 0.81 (0.68, 0.96) 0.80 (0.53, 1.21) Not applicable

HR (95% CI) obtained from a proportional-hazards model: astratified by baseline ECOG PS (0 vs 1), brain metastases at baseline (yes vs no) and prior treatment with bevacizumab (yes vs no); bstratified by TSFLT Q3

Clinical trial identification

NCT00805194

Disclosure

Y.-L. Wu: honoraria for lectures and advisory board meetings from Boehringer Ingelheim, Roche, Lilly, AstraZeneca, Pfizer. B. Gaschler-Markefski, R. Kaiser: patents, royalties, other intellectual property and employment at Boehringer Ingelheim. M. Reck: honoraria for lectures and advisory board meetings from Boehringer Ingelheim, F. Hoffmann-La Roche, Lilly, Merck Sharp & Dohme, Bristol-Myers Squibb, AstraZeneca, Pfizer, Novartis. All other authors have declared no conflicts of interest.