Nintedanib plus docetaxel as second-line therapy in patients with non-small-cell lung cancer of adenocarcinoma histology: a network meta-analysis vs new therapeutic options

Popat, Sanjay; Mellemgaard, Anders; Reck, Martin; Hastedt, Claudia; Griebsch, Ingolf

doi:10.2217/fon-2016-0493

Cited by 19 publications

(18 citation statements)

References 21 publications

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“…Therefore, docetaxel plus AAT might be preferred over immunotherapy in patients with non-sq carcinoma, low PD-L1 expression, and/or more aggressive disease. This hypothesis is also supported by a recent exploratory network meta-analysis [50]. For patients with sq NSCLC, immune checkpoint blockade is mostly the preferred treatment option for second-line treatment.…”

Section: Discussionmentioning

confidence: 65%

Anti-Angiogenics: Their Value in Lung Cancer Therapy

Janning

Loges

2018

Oncol Res Treat

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Lung cancer is the second most common cancer and the leading cause of cancer-related deaths. Different targeted therapies and the introduction of immunotherapy have successfully improved outcome for patients with non-small lung cancer (NSCLC). Anti-angiogenic drugs are an essential component in the treatment of NSCLC patients. The vascular endothelial growth factor (VEGF)-A antibody bevacizumab is approved for first-line treatment of advanced-stage patients in combination with platinum-based chemotherapy. Ramucirumab, a VEGF receptor antibody, and nintedanib, an anti-angiogenic multi-tyrosine kinase inhibitor, are approved for second-line treatment in combination with docetaxel. This review provides a summary of pivotal trials with anti-angiogenic drugs in NSCLC in different settings. We give an overview of how to position anti-angiogenic therapy in the current treatment algorithms and highlight future directions. The identification of predictive biomarkers for patient selection could improve the success of anti-angiogenic drugs and represents an important area of research. In addition, novel therapeutic targets including endothelial metabolomic intermediates and cellular components of the tumor microenvironment could lead to the identification of innovative new targets besides the VEGF axis.

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Section: Discussionmentioning

confidence: 65%

Anti-Angiogenics: Their Value in Lung Cancer Therapy

Janning

Loges

2018

Oncol Res Treat

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“…29 A network meta-analysis published in 2017 analyzed data across multiple randomized controlled trials and evaluated the relative efficacy of nintedanib plus docetaxel compared with other second-line agents in patients with adenocarcinoma histology NSCLC. 30 Regarding both OS and PFS analysis, there was a statistically significant advantage of nintedanib plus docetaxel over monotherapy with docetaxel, erlotinib, and gefitinib. 30 Comparison between nintedanib plus docetaxel and the newer treatment option, ramucirumab plus docetaxel, presented a similar relative efficacy, shown by no difference in either OS or PFS.…”

Section: Introductionmentioning

confidence: 92%

“…30 Regarding both OS and PFS analysis, there was a statistically significant advantage of nintedanib plus docetaxel over monotherapy with docetaxel, erlotinib, and gefitinib. 30 Comparison between nintedanib plus docetaxel and the newer treatment option, ramucirumab plus docetaxel, presented a similar relative efficacy, shown by no difference in either OS or PFS. 30 , Interestingly, when the combination of nintedanib plus docetaxel was compared with nivolumab as monotherapy, programmed death-ligand 1 (PD-L1) expression levels showed an important impact on patient outcomes.…”

Section: Introductionmentioning

confidence: 92%

“…30 Comparison between nintedanib plus docetaxel and the newer treatment option, ramucirumab plus docetaxel, presented a similar relative efficacy, shown by no difference in either OS or PFS. 30 , Interestingly, when the combination of nintedanib plus docetaxel was compared with nivolumab as monotherapy, programmed death-ligand 1 (PD-L1) expression levels showed an important impact on patient outcomes. In those with low PD-L1 expression levels,…”

Section: Introductionmentioning

confidence: 93%

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Real-World Evidence: Multicenter Efficacy and Toxicity Analysis of Nintedanib With Docetaxel as Second-Line Treatment in Mexican Patients With Advanced Lung Adenocarcinoma

Rodríguez-Cid

Campos-Gomez

García-Montes

et al. 2020

JCO Global Oncology

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PURPOSE The LUME-Lung 1 study has brought consistent evidence of the effective use of nintedanib in lung adenocarcinoma as a second line of treatment; however, differences among ethnicities have been found in some studies. METHODS This was a retrospective review among 21 medical centers of 150 patients with a confirmed diagnosis of lung adenocarcinoma, included in a compassionate use program of nintedanib from March 2014 to September 2015. The current study aimed to analyze the effectiveness of nintedanib in combination with docetaxel in the Mexican population, using progression-free survival rate and the best objective response to treatment by RECIST 1.1 as a surrogate of effectiveness. In addition, we examined the toxicity profile of our study population as a secondary end point. RESULTS After exclusion criteria, only 99 patients met the criteria for enrollment in the current study. From the total study population, 53 patients (53.5%) were male and 46 (46.5%) were female, with an average age of 60 years and stage IV as the most prevalent clinical stage at the beginning of the compassionate use program. A total of 48 patients (48.5%) had partial response; 26 (26.3%), stable disease; 4 (4%), complete response; and 16 (16.2%), progression; and 5 (5%) were nonevaluable. We found a median progression-free survival of 5 months (95% CI, 4.3 to 5.7 months). The most common grade 3 or 4 adverse reactions were fatigue (14%) and diarrhea (13%). CONCLUSION Nintedanib, as part of a chemotherapy regimen, is an effective option with an acceptable toxicity profile for advanced lung adenocarcinoma after first-line treatment progression.

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“…It was shown in vitro that anti-VEGFR therapy contributes to normalization of tumor neovascular and enhances antitumor activity. VEGFR-TKIs in combination with chemotherapy results in cancer cell death and rapid tumor shrinkage8. However, whether VEGFR-TKIs in combination with chemotherapy can prolong survival and lower the number of adverse effects (AEs) requires further evaluation.…”

Section: Introductionmentioning

confidence: 99%

VEGFR-TKIs combined with chemotherapy for advanced non-small cell lung cancer: A systematic review

Liu¹,

Zhang²,

Jia³

et al. 2019

J. Cancer

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Introduction: To estimate the efficacy and safety of vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) in combination with chemotherapy for patients with advanced non-small cell lung cancer (NSCLC). Methods: We searched PubMed, PMC database, EMBASE, EBSCO-Medline, Cochrane Central Register of Controlled Trials (CENTRAL), American Society of Clinical Oncology (ASCO), International Association for the Study of Lung Cancer (IASLC) and the European Society of Medical Oncology (ESMO), http://www.clinicaltrials.gov/, CNKI, and Wanfang databases to identify primary research reporting the survival outcomes and safety of VEGFR-TKIs in patients with advanced NSCLC. A meta-analysis was conducted to generate combined hazard ratios (HRs) with 95% confidence intervals (CI) for overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and risk ratios (RRs) with 95% CI for adverse events (AEs). Results: A total of 20 RCTs (8,366 participants) were included. The VEGFR-TKIs resulted in improved PFS (HR 0.82, 95% CI 0.78-0.87), ORR (HR 1.72, 95% CI 1.34-2.22), and DCR (1.45, 1.26-1.67) in patients with advanced NSCLC, but had no impact on OS (HR 0.94, 95% CI 0.89-1.00). The incidence of some high grade (≥ 3) AEs increased, such as hemorrhage, hypertension and neutropenia. Conclusions: Our study demonstrated that regimens with VEGFR-TKIs combined with chemotherapy improved PFS, ORR and DCR in patients with advanced NSCLC, but had no impact on OS. VEGFR-TKIs induced more frequent and serious AEs compared with control therapies.

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Nintedanib plus docetaxel as second-line therapy in patients with non-small-cell lung cancer of adenocarcinoma histology: a network meta-analysis vs new therapeutic options

Abstract: Results demonstrated similar efficacy of nintedanib + docetaxel compared with the new therapeutic options ramucirumab + docetaxel and nivolumab, with potential differences in subgroups according to PD-L1 expression level.

Cited by 19 publications

References 21 publications

Anti-Angiogenics: Their Value in Lung Cancer Therapy

Anti-Angiogenics: Their Value in Lung Cancer Therapy

Real-World Evidence: Multicenter Efficacy and Toxicity Analysis of Nintedanib With Docetaxel as Second-Line Treatment in Mexican Patients With Advanced Lung Adenocarcinoma

VEGFR-TKIs combined with chemotherapy for advanced non-small cell lung cancer: A systematic review

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