Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Current Pulmonology Reports
Published in: Current Pulmonology Reports 2/2013

01-06-2013 | Hot Topic

Targeting angiogenesis in advanced non-small-cell lung cancer: are biomarkers needed?

Authors: G. Metro, M. Cenci, A. Baldi, L. Crinò

Published in: Current Pulmonology Reports | Issue 2/2013

Login to get access

Abstract

Tumor-related angiogenesis is a complex process resulting from a delicate balance between pro and anti-angiogenic factors. Bevacizumab, a fully humanized monoclonal antibody against vascular endothelial growth factor (VEGF), was the first anti-angiogenic therapy to prove effective, in combination with chemotherapy, for treatment of several types of advanced cancer, non-small-cell lung cancer (NSCLC) included. However, as for other types of solid malignancy, no predictive biomarkers of increased sensitivity to bevacizumab or any other anti-angiogenic drugs could be identified in NSCLC, which has had a negative affect on the cost-effectiveness of the targeted therapy performed to block the VEGF pathway. In this review we discuss the most relevant findings from clinical and correlative studies investigating the use of anti-angiogenic therapy for advanced NSCLC, focusing on the need to identify biomarkers for selection of patients suitable for anti-angiogenic therapy.
Literature
1.
2.
Pallis AG, Syrigos KN. Targeting tumor neovasculature in non-small-cell lung cancer. Crit Rev Oncol Hematol. 2012, In press.
3.
• Jain RK, Carmeliet P. SnapShot: Tumor angiogenesis. Cell. 2012;149:1408–1408.e1. Synthetic description on how angiogenesis works and on the current status of anti-angiogenic therapy for solid malignancies.
4.
Cohen MH, Gootenberg J, Keegan P, Pazdur R. FDA drug approval summary: bevacizumab (Avastin) plus Carboplatin and Paclitaxel as first-line treatment of advanced/metastatic recurrent nonsquamous non-small cell lung cancer. Oncologist. 2007;12:713–8.PubMedCrossRef
5.
6.
Sandler A, Gray R, Perry MC, et al. Paclitaxel–carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med. 2006;355:2542–50.PubMedCrossRef
7.
Reck M, von Pawel J, Zatloukal P, et al. Phase III trial of cisplatin plus gemcitabine with either placebo or bevacizumab as first-line therapy for nonsquamous non-small-cell lung cancer: AVAil. J Clin Oncol. 2009;27:1227–34.PubMedCrossRef
8.
Reck M, von Pawel J, Zatloukal P, et al. Overall survival with cisplatin–gemcitabine and bevacizumab or placebo as first-line therapy for nonsquamous non-small-cell lung cancer: results from a randomised phase III trial (AVAiL). Ann Oncol. 2010;21:1804–49.PubMedCrossRef
9.
• Soria JC, Mauguen A, Reck M, et al. Systematic review and meta-analysis of randomised, phase II/III trials adding bevacizumab to platinum-based chemotherapy as first-line treatment in patients with advanced non-small-cell lung cancer. Ann Oncol. 2013;24:20–30. Meta-analysis of randomized studies indicating that bevacizumab significantly prolongs PFS and OS when added to standard platinum-based chemotherapy as first-line therapy for patients with advanced non-squamous NSCLC.PubMedCrossRef
10.
11.
Peters S, Adjei AA, Gridelli C, et al. Metastatic non-small-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2012;23 Suppl 7:vii56–64.PubMedCrossRef
12.
• Reck M, Barlesi F, Crinò L, et al. Predicting and managing the risk of pulmonary haemorrhage in patients with NSCLC treated with bevacizumab: a consensus report from a panel of experts. Ann Oncol. 2012;23:1111–20. Important review of the clinico-pathological factors that predispose to the development of pulmonary haemorrhage while on bevacizumab therapy for advanced non-squamous NSCLC. PubMedCrossRef
13.
Goulart B, Ramsey S. A trial-based assessment of the cost-utility of bevacizumab and chemotherapy versus chemotherapy alone for advanced non-small cell lung cancer. Value Health. 2011;14:836–45.PubMedCrossRef
14.
Jayson GC, de Haas S, Delmar P, et al. Evaluation of plasma VEGF-A as a potential predictive pan-tumor biomarker for bevacizumab. [abstract 804]. Presented at the European Multidisciplinary Cancer Congress. Stockholm, Sweden; September 23–27, 2011.
15.
Dowlati A, Gray R, Sandler AB, et al. Cell adhesion molecules, vascular endothelial growth factor, and basic fibroblast growth factor in patients with non-small cell lung cancer treated with chemotherapy with or without bevacizumab—an Eastern Cooperative Oncology Group Study. Clin Cancer Res. 2008;14:1407–12.PubMedCrossRef
16.
Hegde PS, Jubb AM, Chen D, et al. Predictive Impact of Circulating Vascular Endothelial Growth Factor in 4 Phase III Trials Evaluating Bevacizumab. Clin Cancer Res. 2013;19:929–37.
17.
Mok T, Gorbunova V, Juhasz E, et al. Biomarker analysis in BO21015 (ABIGAIL), a phase II randomised study of first-line bevacizumab (BEV) combined with carboplatin–gemcitabine (CG) or carboplatin–paclitaxel (CP) in patients (pts) with advanced or recurrent non-squamous non-small cell lung cancer (NSCLC). [abstract 9003]. Presented at the European Multidisciplinary Cancer Congress. Stockholm, Sweden; September 23–27, 2011.
18.
Reck M, Gorbunova V, Juhasz E, et al. Tumor biomarker and plasma time course data from ABIGAIL, a phase II study of 1st-line bevacizumab + chemotherapy in advanced non-squamous non-small-cell lung cancer (ns-NSCLC). [abstract 1236PD]. Presented at the 37th European Society for Medical Oncology Congress. Vienna, Austria; September 28–October 2, 2012.
19.
Pallaud C, Reck M, Juhasz E, et al. Clinical genotyping and efficacy outcomes: exploratory biomarker data from the phase II ABIGAIL study of 1st-line bevacizumab + chemotherapy in non-squamous non-small-cell lung cancer (ns-NSCLC). [abstract 1239P]. Presented at the 37th European Society for Medical Oncology Congress. Vienna, Austria; September 28–October 2, 2012.
20.
Zhang W, Dahlberg SE, Yang D, et al. Genetic variants in angiogenesis pathway associated with clinical outcome in NSCLC patients (pts) treated with bevacizumab in combination with carboplatin and paclitaxel: Subset pharmacogenetic analysis of ECOG 4599. [abstract 8032]. Presented at the American Society of Clinical Oncology Congress. Orlando, USA; May 29–June 2, 2012.
21.
Schneider BP, Wang M, Radovich M, et al. Association of vascular endothelial growth factor and vascular endothelial growth factor receptor-2 genetic polymorphisms with outcome in a trial of paclitaxel compared with paclitaxel plus bevacizumab in advanced breast cancer: ECOG 2100. J Clin Oncol. 2008;26:4672–8.PubMedCrossRef
22.
Lambrechts D, Claes B, Delmar P, et al. VEGF pathway genetic variants as biomarkers of treatment outcome with bevacizumab: an analysis of data from the AViTA and AVOREN randomised trials. Lancet Oncol. 2012;13:724–33.PubMedCrossRef
23.
Farhat FS, Tfayli A, Fakhruddin N, et al. Expression, prognostic and predictive impact of VEGF and bFGF in non-small cell lung cancer. Crit Rev Oncol Hematol. 2012;84:149–60.PubMedCrossRef
24.
Schneider BP, Gray R, Radovich M, et al. Prognostic and predictive value of tumor VEGF gene amplification in metastatic breast cancer treated with paclitaxel with and without bevacizumab; results from ECOG 2100 trial. Clin Cancer Res. 2013;19:1281–9.
25.
Gatzemeier U, von Pawel J, Vynnychenko I, et al. First-cycle rash and survival in patients with advanced non-small-cell lung cancer receiving cetuximab in combination with first-line chemotherapy: a subgroup analysis of data from the FLEX phase 3 study. Lancet Oncol. 2011;12:30–7.PubMedCrossRef
26.
Dahlberg SE, Sandler AB, Brahmer JR, et al. Clinical course of advanced non-small-cell lung cancer patients experiencing hypertension during treatment with bevacizumab in combination with carboplatin and paclitaxel on ECOG 4599. J Clin Oncol. 2010;28:949–54.PubMedCrossRef
27.
Mir O, Coriat R, Cabanes L, et al. An observational study of bevacizumab-induced hypertension as a clinical biomarker of antitumor activity. Oncologist. 2011;16:1325–32.PubMedCrossRef
28.
Heymach JV, Paz-Ares L, De Braud F, et al. Randomized phase II study of vandetanib alone or with paclitaxel and carboplatin as first-line treatment for advanced non-small-cell lung cancer. J Clin Oncol. 2008;26:5407–15.PubMedCrossRef
29.
Goss GD, Arnold A, Shepherd FA, et al. Randomized, double-blind trial of carboplatin and paclitaxel with either daily oral cediranib or placebo in advanced non-small-cell lung cancer: NCIC clinical trials group BR24 study. J Clin Oncol. 2010;28:49–55.PubMedCrossRef
30.
Laurie SA, Solomon BJ, Seymour L, et al. A randomized double-blind trial of carboplatin plus paclitaxel (CP) with daily oral cediranib (CED), an inhibitor of vascular endothelial growth factor receptors, or placebo (PLA) in patients (pts) with previously untreated advanced non-small cell lung cancer (NSCLC): NCIC Clinical Trials Group study BR29. [abstract 7511]. Presented at the American Society of Clinical Oncology Congress. Chicago, USA; June 1–5, 2012.
31.
Scagliotti G, Novello S, von Pawel J, et al. Phase III study of carboplatin and paclitaxel alone or with sorafenib in advanced non-small-cell lung cancer. J Clin Oncol. 2010;28:1835–42.PubMedCrossRef
32.
Paz-Ares LG, Biesma B, Heigener D, et al. Phase III, randomized, double-blind, placebo-controlled trial of gemcitabine/cisplatin alone or with sorafenib for the first-line treatment of advanced, nonsquamous non-small-cell lung cancer. J Clin Oncol. 2012;30:3084–92.PubMedCrossRef
33.
Scagliotti GV, Vynnychenko I, Park K, et al. International, randomized, placebo-controlled, double-blind phase III study of motesanib plus carboplatin/paclitaxel in patients with advanced nonsquamous non-small-cell lung cancer: MONET1. J Clin Oncol. 2012;30:2829–36.PubMedCrossRef
34.
Herbst RS, Sun Y, Eberhardt WE, et al. Vandetanib plus docetaxel versus docetaxel as second-line treatment for patients with advanced non-small-cell lung cancer (ZODIAC): a double-blind, randomised, phase 3 trial. Lancet Oncol. 2010;11:619–26.PubMedCrossRef
35.
de Boer RH, Arrieta Ó, Yang CH, et al. Vandetanib plus pemetrexed for the second-line treatment of advanced non-small-cell lung cancer: a randomized, double-blind phase III trial. J Clin Oncol. 2011;29:1067–74.PubMedCrossRef
36.
Metro G, Minotti V, Crinò L. Years of sorafenib investigation in advanced non-small cell lung cancer: is there a ‘NExUS’ linking an unsuccessful treatment and a potentially active one? J Thorac Dis. 2012;4(6):635–8.PubMed
37.
Takezawa K, Okamoto I, Yonesaka K, et al. Sorafenib inhibits non-small cell lung cancer cell growth by targeting B-RAF in KRAS wild-type cells and C-RAF in KRAS mutant cells. Cancer Res. 2009;69:6515–21.PubMedCrossRef
38.
Pan F, Tian J, Zhang X, et al. Synergistic interaction between sunitinib and docetaxel is sequence dependent in human non-small lung cancer with EGFR TKIs-resistant mutation. J Cancer Res Clin Oncol. 2011;137:1397–408.PubMedCrossRef
39.
40.
Je Y, Schutz FA, Choueiri TK. Risk of bleeding with vascular endothelial growth factor receptor tyrosine-kinase inhibitors sunitinib and sorafenib: a systematic review and meta-analysis of clinical trials. Lancet Oncol. 2009;10:967–74.PubMedCrossRef
41.
Choueiri TK, Schutz FA, Je Y, et al. Risk of arterial thromboembolic events with sunitinib and sorafenib: a systematic review and meta-analysis of clinical trials. J Clin Oncol. 2010;28:2280–5.PubMedCrossRef
42.
Schutz FA, Je Y, Richards CJ, Choueiri TK. Meta-analysis of randomized controlled trials for the incidence and risk of treatment-related mortality in patients with cancer treated with vascular endothelial growth factor tyrosine kinase inhibitors. J Clin Oncol. 2012;30:871–7.PubMedCrossRef
43.
Stewart MW. Aflibercept (VEGF-TRAP): the next anti-VEGF drug. Inflamm Allergy Drug Targets. 2011;10:497–508.PubMedCrossRef
44.
Van Cutsem E, Tabernero J, Lakomy R, et al. Addition of aflibercept to fluorouracil, leucovorin, and irinotecan improves survival in a phase III randomized trial in patients with metastatic colorectal cancer previously treated with an oxaliplatin-based regimen. J Clin Oncol. 2012;30:3499–506.PubMedCrossRef
45.
Ramlau R, Gorbunova V, Ciuleanu TE, et al. Aflibercept and docetaxel versus docetaxel alone after platinum failure in patients with advanced or metastatic non-small-cell lung cancer: a randomized, controlled phase III trial. J Clin Oncol. 2012;30:3640–7.PubMedCrossRef
46.
47.
Lara Jr PN, Douillard JY, Nakagawa K, et al. Randomized phase III placebo-controlled trial of carboplatin and paclitaxel with or without the vascular disrupting agent vadimezan (ASA404) in advanced non-small-cell lung cancer. J Clin Oncol. 2011;29:2965–71.PubMedCrossRef
48.
Natale RB, Bodkin D, Govindan R, et al. Vandetanib versus gefitinib in patients with advanced non-small-cell lung cancer: results from a two-part, double-blind, randomized phase ii study. J Clin Oncol. 2009;27:2523–9.PubMedCrossRef
49.
Heymach JV, Johnson BE, Prager D, et al. Randomized, placebo-controlled phase II study of vandetanib plus docetaxel in previously treated non small-cell lung cancer. J Clin Oncol. 2007;25:4270–7.PubMedCrossRef
50.
Hanrahan EO, Ryan AJ, Mann H, et al. Baseline vascular endothelial growth factor concentration as a potential predictive marker of benefit from vandetanib in non-small cell lung cancer. Clin Cancer Res. 2009;15:3600–9.PubMedCrossRef
51.
Hanrahan EO, Lin HY, Kim ES, et al. Distinct patterns of cytokine and angiogenic factor modulation and markers of benefit for vandetanib and/or chemotherapy in patients with non-small-cell lung cancer. J Clin Oncol. 2010;28:193–201.PubMedCrossRef
52.
Nikolinakos PG, Altorki N, Yankelevitz D, et al. Plasma cytokine and angiogenic factor profiling identifies markers associated with tumor shrinkage in early-stage non-small cell lung cancer patients treated with pazopanib. Cancer Res. 2010;70:2171–9.PubMedCrossRef
53.
O’Connor JP, Jackson A, Parker GJ, et al. Dynamic contrast-enhanced MRI in clinical trials of antivascular therapies. Nat Rev Clin Oncol. 2012;9:167–77.PubMedCrossRef
Metadata
Title
Targeting angiogenesis in advanced non-small-cell lung cancer: are biomarkers needed?
Authors
G. Metro
M. Cenci
A. Baldi
L. Crinò
Publication date
01-06-2013
Publisher
Current Science Inc.
Published in
Current Pulmonology Reports / Issue 2/2013
Electronic ISSN: 2199-2428
DOI
https://doi.org/10.1007/s13665-013-0046-0

Other articles of this Issue 2/2013

Current Pulmonology Reports 2/2013 Go to the issue

Sleep Medicine (V Castronovo, Section Editor)

Chronic obstructive pulmonary disease and sleep

Pleural Diseases and Mesothelioma (YCG Lee, Section Editor)

EGFR mutations in malignant pleural effusions from lung cancer

Pleural Diseases and Mesothelioma (YCG Lee, Section Editor)

Advantages of indwelling pleural catheters for management of malignant pleural effusions

Pleural Diseases and Mesothelioma (YCG Lee, Section Editor)

New agents for pleurodesis

Pleural Diseases and Mesothelioma (YCG Lee, Section Editor)

Prognostic factors for malignant pleural mesothelioma

Pleural Diseases and Mesothelioma (YCG Lee, Section Editor)

Management options for the complicated pleural space
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits