Abstract 983
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; 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). 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.
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 Results
Conclusions
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
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.