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J. Douillard
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MINI 17 - WT EGFR, Angiogenesis and OMD (ID 131)
- Event: WCLC 2015
- Type: Mini Oral
- Track: Treatment of Advanced Diseases - NSCLC
- Presentations: 2
- Moderators:R. Feld, R. Dziadziuszko
- Coordinates: 9/08/2015, 16:45 - 18:15, Mile High Ballroom 4a-4f
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MINI17.07 - Efficacy of Nintedanib/Docetaxel after Bevacizumab, Pemetrexed or Taxanes Therapy (ID 1521)
16:45 - 18:15 | Author(s): J. Douillard
- Abstract
- Presentation
Background:
Nintedanib is a triple angiokinase inhibitor of receptors for vascular endothelial growth factor (VEGF), platelet-derived growth factor and fibroblast growth factor. The randomized, placebo-controlled, Phase III LUME-Lung 1 study (NCT00805194; 1199.13) investigating nintedanib/docetaxel was the first trial of an antiangiogenic agent to demonstrate significant overall survival (OS) benefit in previously treated patients with non-small cell lung cancer (NSCLC) of adenocarcinoma histology; nintedanib/docetaxel is approved in the European Union for the treatment of patients with locally advanced, metastatic or locally recurrent NSCLC of adenocarcinoma histology after 1[st]-line chemotherapy. Here we report LUME-Lung 1 data from the adenocarcinoma population who received 1[st]-line chemotherapy containing bevacizumab, pemetrexed or taxanes.
Methods:
In LUME-Lung 1, 1314 patients with Stage IIIB/IV recurrent NSCLC received either nintedanib/docetaxel or placebo/docetaxel. Primary endpoint was centrally assessed progression-free survival (PFS); OS was a key secondary endpoint. Prior treatment with anti-VEGF agent bevacizumab was a stratification factor. Analyses of the adenocarcinoma population (n=658) according to prior treatment with bevacizumab (n=45 in either arm), pemetrexed (1[st]-line [n=126] or maintenance [n=27]) or taxanes (n=142) were performed to determine if 1[st]-line regimens could influence subsequent outcomes for nintedanib/docetaxel.
Results:
Patient characteristics were generally well-balanced across prior-treatment subgroups. For the adenocarcinoma population, there was no interaction between 1[st]-line treatment with bevacizumab, pemetrexed or taxanes and treatment outcome with nintedanib/docetaxel. Independent of pretreatment, nintedanib/docetaxel-treated adenocarcinoma patients had an OS benefit (Table). In the overall patient population, efficacy outcomes for these subgroups were also similar regardless of prior treatment. Furthermore, there was no significant effect on nintedanib/docetaxel outcomes for the few adenocarcinoma patients who received maintenance pemetrexed. The adverse event (AE) profile for nintedanib/docetaxel in each subgroup was consistent with that reported for the adenocarcinoma population in LUME-Lung 1, with diarrhea and reversible liver enzyme elevations among the more frequently reported AEs. Among patients who received nintedanib/docetaxel, there was no difference between prior-treatment subgroups in the frequency of AEs commonly associated with the prior treatment, such as hypertension with bevacizumab, mucositis with pemetrexed and peripheral neuropathy with taxanes.
Conclusion:
In LUME-Lung 1, regardless of whether a patient with NSCLC of adenocarcinoma histology received 1[st]-line chemotherapy containing bevacizumab, pemetrexed or taxanes, subsequent treatment with nintedanib/docetaxel led to improved OS.Table: OS results in patients with NSCLC of adenocarcinoma tumor histology stratified by ± prior 1st-line bevacizumab, pemetrexed or taxanes treatment
BEV, bevacizumab; CI, confidence interval; HR, hazard ratio; N/D, nintedanib/docetaxel; NSCLC, non-small cell lung cancer; OS, overall survival; PEM, pemetrexed; Pl/D, placebo/docetaxel; TAX, taxanes.No BEV BEV No PEM PEM No TAX TAX N/D Pl/D N/D Pl/D N/D Pl/D N/D Pl/D N/D Pl/D N/D Pl/D Patients, n 298 315 24 21 261 271 61 65 245 271 77 65 Median OS, months 12.6 10.6 14.9 8.7 13.4 10.8 12.0 8.0 12.2 10.3 15.1 11.6 HR (95% CI) 0.85 (0.71–1.01) 0.61 (0.31–1.20) 0.83 (0.68–1.00) 0.79 (0.53–1.18) 0.86 (0.71–1.05) 0.75 (0.51–1.11) Interaction p-value p=0.24 p=0.90 p=0.61
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MINI17.08 - Tumor Growth Over Time with Nintedanib/Docetaxel or Placebo/Docetaxel in Adenocarcinoma NSCLC: Analysis From the LUME-Lung 1 Study (ID 1405)
16:45 - 18:15 | Author(s): J. Douillard
- Abstract
Background:
Nintedanib (N; Vargatef[®]), a triple angiokinase inhibitor, is approved in the EU in combination with docetaxel (D) for the treatment of patients with advanced NSCLC of adenocarcinoma histology (ACH) after 1[st]-line chemotherapy. In the randomized, placebo-controlled, Phase III LUME-Lung 1 study (NCT00805194; 1199.13), N+D significantly improved overall survival (OS; secondary endpoint) vs D in patients with ACH (median OS: 12.6 vs 10.3 months (m); HR: 0.83 [95% CI: 0.70–0.99]; p=0.0359) and in patients who progressed either during or within 9 m of 1[st]-line therapy (time[T]<9m) (median OS: 10.9 vs 7.9 m; HR: 0.75 [95% CI: 0.60–0.92]; p=0.0073). We explored the impact of on tumor growth over time as a treatment effect of N+D, with a specific focus on early progressors (T<9m) and patients who had progressive disease as best response to 1[st]-line therapy (PD-FLT).
Methods:
Tumor growth was evaluated using all available tumor measurements. Mixed-effects models were used to quantify the non-linear individual relationships between time from randomization and tumor burden, measured as the sum of longest diameter of target lesions (SLD) and assessed by independent central review (RECIST 1.0). Analyses were conducted for the entire population of patients with ACH, T<9m and PD-FLT.
Results:
Estimated mean baseline SLD was 82.5 mm in all patients with ACH, 88.3 mm in T<9m and 98.1 mm in PD-FLT. N+D showed a significant reduction of tumor growth over time (p<0.0001) in patients with ACH compared to D. Treatment difference at 6 months (SLD D group – SLD N+D group) for patients with ACH was 9.7 mm. This treatment difference was even more pronounced in the T<9m group (16.8 mm) and in patients with PD-FLT (19.7 mm). Tumor growth over time for N+D showed a non-linear J-shaped curve, indicating a decline in SLD at the beginning of treatment, which was maintained over time followed by a linear increase (see Figure for curves for the T<9m group). This relationship was consistently observed between populations. For patients treated with D, a linear increase in SLD from baseline over time in all ACH patients, T<9m and PD-FLT was observed. Figure 1
Conclusion:
In the LUME-Lung 1 study, N+D significantly decreased tumor burden and decelerated tumor growth over time compared to D in all patients with ACH and in the groups of patients with the poorest prognosis.
