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Emerging treatments and combinations in the management of NSCLC: clinical potential of nintedanib.

Reck M, Mellemgaard A - Biologics (2015)

Bottom Line: There remains an unmet need for effective, well-tolerated treatment options in advanced non-small cell lung cancer (NSCLC) to alleviate the disease burden for a broad selection of patients.In this study, which led to the approval of nintedanib, addition of nintedanib to docetaxel significantly improved overall survival in patients with adenocarcinoma histology.Nintedanib demonstrated a manageable safety profile in combination with docetaxel.

View Article: PubMed Central - PubMed

Affiliation: Department of Thoracic Oncology, Lung Clinic Grosshansdorf, and member of the Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany.

ABSTRACT
There remains an unmet need for effective, well-tolerated treatment options in advanced non-small cell lung cancer (NSCLC) to alleviate the disease burden for a broad selection of patients. Nintedanib is a potent, oral, triple angiokinase inhibitor of vascular endothelial growth factor, fibroblast growth factor, and platelet-derived growth factor, and was recently approved in Europe for use in combination with docetaxel for the treatment of adults with locally advanced, metastatic, or locally recurrent NSCLC of adenocarcinoma tumor histology, following first-line chemotherapy. Nintedanib has been investigated extensively in preclinical research and in a number of clinical studies, the most important of which was the Phase III LUME-Lung 1 study, which investigated nintedanib in combination with docetaxel in patients with advanced NSCLC after failure of first-line chemotherapy. In this study, which led to the approval of nintedanib, addition of nintedanib to docetaxel significantly improved overall survival in patients with adenocarcinoma histology. Nintedanib demonstrated a manageable safety profile in combination with docetaxel. This review focuses on the clinical experience with nintedanib in NSCLC and discusses the clinical potential of this agent for use in combination with chemotherapy.

No MeSH data available.


Related in: MedlinePlus

Kaplan–Meier curves for patients treated with nintedanib plus docetaxel or placebo plus docetaxel.Notes: Overall survival at the time of final analysis in (A) patients with adenocarcinoma histology and time since start of first-line therapy of less than 9 months; (B) all patients with adenocarcinoma histology; (C) total population. Patients without documented death were censored at the date of last contact when the patient was known to be alive. Reprinted from Lancet Oncol, Vol 15, Reck M, et al, Docetaxel plus nintedanib versus docetaxel plus placebo in patients with previously treated non-small cell lung cancer (LUME-Lung 1): a phase 3, double-blind, randomised trial, 143–155, Copyright (2014), with permission from Elsevier.31Abbreviations: CI, confidence interval; HR, hazard ratio.
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f2-btt-9-047: Kaplan–Meier curves for patients treated with nintedanib plus docetaxel or placebo plus docetaxel.Notes: Overall survival at the time of final analysis in (A) patients with adenocarcinoma histology and time since start of first-line therapy of less than 9 months; (B) all patients with adenocarcinoma histology; (C) total population. Patients without documented death were censored at the date of last contact when the patient was known to be alive. Reprinted from Lancet Oncol, Vol 15, Reck M, et al, Docetaxel plus nintedanib versus docetaxel plus placebo in patients with previously treated non-small cell lung cancer (LUME-Lung 1): a phase 3, double-blind, randomised trial, 143–155, Copyright (2014), with permission from Elsevier.31Abbreviations: CI, confidence interval; HR, hazard ratio.

Mentions: The primary study endpoint of LUME-Lung 1 was met; progression-free survival was significantly improved in the nintedanib plus docetaxel group compared with the placebo plus docetaxel group (3.4 months [95% confidence interval (CI) 2.9–3.9] versus 2.7 months [95% CI 2.6–2.8]; HR 0.79 [95% CI 0.68–0.92]; P=0.0019).31 Similar results were noted in patients with adenocarcinoma and patients with squamous cell carcinoma.31 In the adenocarcinoma population, the median overall survival was greater than 1 year in the nintedanib plus docetaxel group and significantly greater than in the placebo plus docetaxel group (12.6 months [95% CI 10.6–15.1] versus 10.3 months [95% CI 8.6–12.2]; HR 0.83 [95% CI 0.70–0.99]; P=0.0359, Figure 2).31 Improvement was also observed in patients with adenocarcinoma histology who progressed rapidly, within 9 months of the start of first-line therapy; the median overall survival was 10.9 months with nintedanib plus docetaxel versus 7.9 months with placebo plus docetaxel (HR 0.75, 95% CI 0.60–0.92; P=0.0073, Figure 2).31,33 For both the overall adenocarcinoma population and the adenocarcinoma patients who progressed rapidly, the probability of survival at 12 and 24 months was greater for patients treated with nintedanib plus docetaxel versus patients treated with placebo plus docetaxel. In the overall adenocarcinoma population, 12 month overall survival was 52.7% with nintedanib plus docetaxel compared with 44.7% with placebo and docetaxel, and 24 month overall survival was 25.7% compared with 19.1%. In the adenocarcinoma population of patients who progressed rapidly, 12 month overall survival was 46.8% with nintedanib plus docetaxel versus 34.3% with placebo plus docetaxel; 24 month overall survival was 20.7% versus 10.4%. An exploratory analysis was also conducted in patients with adenocarcinoma refractory to first-line treatment chemotherapy. These patients had achieved only progressive disease as the best response to first-line therapy prior to entry into the LUME-Lung 1 trial.31,33 The median overall survival was 9.8 months with nintedanib plus docetaxel versus 6.3 months with placebo plus docetaxel (HR 0.62, 95% CI 0.41–0.94; P=0.0246, Figure 3) in this subpopulation; the probability of survival was higher in patients treated with nintedanib plus docetaxel versus placebo plus docetaxel at 12 months (43.0% versus 24.6%) and 24 months (21.5% versus 5.3%).31


Emerging treatments and combinations in the management of NSCLC: clinical potential of nintedanib.

Reck M, Mellemgaard A - Biologics (2015)

Kaplan–Meier curves for patients treated with nintedanib plus docetaxel or placebo plus docetaxel.Notes: Overall survival at the time of final analysis in (A) patients with adenocarcinoma histology and time since start of first-line therapy of less than 9 months; (B) all patients with adenocarcinoma histology; (C) total population. Patients without documented death were censored at the date of last contact when the patient was known to be alive. Reprinted from Lancet Oncol, Vol 15, Reck M, et al, Docetaxel plus nintedanib versus docetaxel plus placebo in patients with previously treated non-small cell lung cancer (LUME-Lung 1): a phase 3, double-blind, randomised trial, 143–155, Copyright (2014), with permission from Elsevier.31Abbreviations: CI, confidence interval; HR, hazard ratio.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4494183&req=5

f2-btt-9-047: Kaplan–Meier curves for patients treated with nintedanib plus docetaxel or placebo plus docetaxel.Notes: Overall survival at the time of final analysis in (A) patients with adenocarcinoma histology and time since start of first-line therapy of less than 9 months; (B) all patients with adenocarcinoma histology; (C) total population. Patients without documented death were censored at the date of last contact when the patient was known to be alive. Reprinted from Lancet Oncol, Vol 15, Reck M, et al, Docetaxel plus nintedanib versus docetaxel plus placebo in patients with previously treated non-small cell lung cancer (LUME-Lung 1): a phase 3, double-blind, randomised trial, 143–155, Copyright (2014), with permission from Elsevier.31Abbreviations: CI, confidence interval; HR, hazard ratio.
Mentions: The primary study endpoint of LUME-Lung 1 was met; progression-free survival was significantly improved in the nintedanib plus docetaxel group compared with the placebo plus docetaxel group (3.4 months [95% confidence interval (CI) 2.9–3.9] versus 2.7 months [95% CI 2.6–2.8]; HR 0.79 [95% CI 0.68–0.92]; P=0.0019).31 Similar results were noted in patients with adenocarcinoma and patients with squamous cell carcinoma.31 In the adenocarcinoma population, the median overall survival was greater than 1 year in the nintedanib plus docetaxel group and significantly greater than in the placebo plus docetaxel group (12.6 months [95% CI 10.6–15.1] versus 10.3 months [95% CI 8.6–12.2]; HR 0.83 [95% CI 0.70–0.99]; P=0.0359, Figure 2).31 Improvement was also observed in patients with adenocarcinoma histology who progressed rapidly, within 9 months of the start of first-line therapy; the median overall survival was 10.9 months with nintedanib plus docetaxel versus 7.9 months with placebo plus docetaxel (HR 0.75, 95% CI 0.60–0.92; P=0.0073, Figure 2).31,33 For both the overall adenocarcinoma population and the adenocarcinoma patients who progressed rapidly, the probability of survival at 12 and 24 months was greater for patients treated with nintedanib plus docetaxel versus patients treated with placebo plus docetaxel. In the overall adenocarcinoma population, 12 month overall survival was 52.7% with nintedanib plus docetaxel compared with 44.7% with placebo and docetaxel, and 24 month overall survival was 25.7% compared with 19.1%. In the adenocarcinoma population of patients who progressed rapidly, 12 month overall survival was 46.8% with nintedanib plus docetaxel versus 34.3% with placebo plus docetaxel; 24 month overall survival was 20.7% versus 10.4%. An exploratory analysis was also conducted in patients with adenocarcinoma refractory to first-line treatment chemotherapy. These patients had achieved only progressive disease as the best response to first-line therapy prior to entry into the LUME-Lung 1 trial.31,33 The median overall survival was 9.8 months with nintedanib plus docetaxel versus 6.3 months with placebo plus docetaxel (HR 0.62, 95% CI 0.41–0.94; P=0.0246, Figure 3) in this subpopulation; the probability of survival was higher in patients treated with nintedanib plus docetaxel versus placebo plus docetaxel at 12 months (43.0% versus 24.6%) and 24 months (21.5% versus 5.3%).31

Bottom Line: There remains an unmet need for effective, well-tolerated treatment options in advanced non-small cell lung cancer (NSCLC) to alleviate the disease burden for a broad selection of patients.In this study, which led to the approval of nintedanib, addition of nintedanib to docetaxel significantly improved overall survival in patients with adenocarcinoma histology.Nintedanib demonstrated a manageable safety profile in combination with docetaxel.

View Article: PubMed Central - PubMed

Affiliation: Department of Thoracic Oncology, Lung Clinic Grosshansdorf, and member of the Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany.

ABSTRACT
There remains an unmet need for effective, well-tolerated treatment options in advanced non-small cell lung cancer (NSCLC) to alleviate the disease burden for a broad selection of patients. Nintedanib is a potent, oral, triple angiokinase inhibitor of vascular endothelial growth factor, fibroblast growth factor, and platelet-derived growth factor, and was recently approved in Europe for use in combination with docetaxel for the treatment of adults with locally advanced, metastatic, or locally recurrent NSCLC of adenocarcinoma tumor histology, following first-line chemotherapy. Nintedanib has been investigated extensively in preclinical research and in a number of clinical studies, the most important of which was the Phase III LUME-Lung 1 study, which investigated nintedanib in combination with docetaxel in patients with advanced NSCLC after failure of first-line chemotherapy. In this study, which led to the approval of nintedanib, addition of nintedanib to docetaxel significantly improved overall survival in patients with adenocarcinoma histology. Nintedanib demonstrated a manageable safety profile in combination with docetaxel. This review focuses on the clinical experience with nintedanib in NSCLC and discusses the clinical potential of this agent for use in combination with chemotherapy.

No MeSH data available.


Related in: MedlinePlus