VEGF Inhibition: Therapy-Indicating and Prognostic Biomarkers, 2011

Report Summary

Vascular Endothelial Growth Factor (VEGF), which plays an important role in angiogenesis, has been extensively studied and over-expression is seen in many cancers. Today, VEGF is targeted using antibodies and tyrosine kinase inhibitors, and antiangiogenic therapy is a standard treatment for many cancers, including colorectal and non-small cell lung cancer.

While VEGF inhibitors such as bevacizumab (Avastin®) provide valuable treatment options, these benefits are not seen in all patients and cancer types. Today, there is an urgent need for predictive biomarkers to enable those patients most likely to benefit from VEGF inhibition, to be identified. This report provides a review of findings to date on biomarkers associated with the use bevacizumab (Avastin®); both therapy-indicating and prognostic.

The identification of therapy-indicating and prognostic biomarkers relating to antiangiogenic therapy is in its early stages, however important advances have been made. This report identifies the latest findings on ten different cancers and includes an evaluation of candidate biomarkers as a basis for interpreting patient outcomes according to RECIST criteria, and evaluates existing bevacizumab-containing treatments and drug combinations.

Key content:

• A comprehensive review of clinical studies that have identified biomarkers that are either therapy-indicating in respect of bevacizumab (Avastin®) or indicative of patient prognosis
• Biomarkers identified or further evaluated in the last three years, up until October 2011. From a background of extensive research on bevacizumab (Avastin®) and VEGF-related biomarkers, the most important findings have been identified for their significance and value to patients and in designing clinical trials
• Covering more than ten cancers including colorectal, ovarian, renal, breast, pancreatic, prostate, lung and liver cancers
• Findings based on clinical trial findings including patient numbers, statistics and RECIST criteria
• Studies indicate drug type associations together with comparative therapies
• Descriptions and explanation of all biomarkers identified roteins, genotypes, imaging etc)
• Biomarker associations are categorised according to three broad criteria, namely “positive-therapy-indicating” (response, improved response, improved outcome or prognosis), “non-therapy-indicating” (no differences in tumour response, outcome or prognosis) and “negative-therapy-indicating” (adverse events, poor outcome or prognosis)

Table of Contents

Table of Contents

Executive Summary

Chapter-1: Background
1.1. VEGF Inhibition
1.2. Bevacizumab
1.3. Biomarkers
1.4. This Report

Chapter-2: Colorectal Cancer: Candidate Biomarkers identified in Patients receiving Bevacizumab-containing Therapies
Summary
2.1. Introduction
2.2. Glycoprotein
2.3. Protein
2.4. Protein
2.5. Cells
2.6. Genetic
2.7. Physical
2.8. Genetic
2.9. Protein
2.10. Proteins
2.11. Proteins and Genetic
2.12. Image
2.13. Proteins
2.14. Protein

Chapter-3: Breast Cancer: Candidate Biomarkers identified in Patients receiving Bevacizumab-containing Therapies
Summary
3.1. Introduction
3.2. Protein
3.3. Protein
3.4. Protein
3.5. Protein
3.6. Protein
3.7. Genetic
3.8. Protein

Chapter-4: Renal Cancer: Candidate Biomarkers identified in Patients receiving Bevacizumab-containing Therapies
Summary
4.1. Introduction
4.2. Image
4.3. Protein
4.4. Physical
4.5. Protein
4.6. Body Characteristic

Chapter-5: Ovarian Cancer: Candidate Biomarkers identified in Patients receiving Bevacizumab-containing Therapies
Summary
5.1. Introduction
5.2. Proteins
5.3. Proteins
5.4. Proteins
5.5. Proteins

Chapter-6: Lung Cancer: Candidate Biomarkers identified in Patients receiving Bevacizumab-containing Therapies
Summary
6.1. Introduction
6.2. Physical Parameter
6.3. Protein
6.4. Genetic
6.5. Protein

Chapter-7: Liver Cancer: Candidate Biomarkers identified in Patients receiving Bevacizumab-containing Therapies
Summary
7.1. Introduction
7.2. Protein
7.3. Image

Chapter-8: Other Cancers: Candidate Biomarkers identified in Patients receiving Bevacizumab-containing Therapies
Summary
8.1. Introduction
8.2. Proteins
8.3. Proteins
8.4. Protein
8.5. Protein
8.6. Physical
8.7. Physical
8.8. Physical

Chapter-9: Discussion
9.1. Overview
9.2. Colorectal Cancer
9.3. Breast Cancer:
9.4. Renal Cancer:
9.5. Ovarian Cancer
9.6. Lung Cancer
9.7. Liver Cancer
9.8. Other Cancers
9.9. Conclusions

List of Tables

Table 2.1: Candidates biomarkers identified in colorectal cancer patients receiving bevacizumab-containing therapies (cancer, biomarker, biomarker type, drug therapies)
Table 3.1: Candidates biomarkers identified in breast cancer patients receiving bevacizumab-containing therapies (cancer, biomarker, biomarker type, drug therapies)
Table 4.1: Candidates biomarkers identified in renal cancer patients receiving bevacizumab-containing therapies (cancer, biomarker, biomarker type, drug therapies)
Table 5.1: Candidates biomarkers identified in ovarian cancer patients receiving bevacizumab-containing therapies (cancer, biomarker, biomarker type, drug therapies)
Table 6.1: Candidates biomarkers identified in lung cancer patients receiving bevacizumab-containing therapies (cancer, biomarker, biomarker type, drug therapies)
Table 7.1: Candidates biomarkers identified in liver cancer patients receiving bevacizumab-containing therapies (cancer, biomarker, biomarker type, drug therapies)
Table 8.1: Candidates biomarkers identified in other cancer patients receiving bevacizumab-containing therapies (cancer, biomarker, biomarker type, drug therapies)
Table 9.1: Protein candidate biomarkers identified in cancer patients receiving bevacizumab-containing therapies (cancer, biomarker, biomarker type, drug therapies)
Table 9.2: Genetic candidate biomarkers identified in cancer patients receiving bevacizumab-containing therapies (cancer, biomarker, biomarker type, drug therapies)
Table 9.3: Image-based candidate biomarkers identified in cancer patients receiving bevacizumab-containing therapies (cancer, biomarker, biomarker type, drug therapies)
Table 9.4: Other candidate biomarkers identified in cancer patients receiving bevacizumab-containing therapies (cancer, biomarker, biomarker type, drug therapies)

List of Figures

Figure 9.1: Candidate biomarkers types identified in cancer patients receiving bevacizumab-containing therapies
Figure 9.2: Cancer types evaluated for biomarkers identified in cancer patients receiving bevacizumab-containing therapies
Figure 9.3: Author countries (identified in this report) of cancers evaluated for biomarkers identified in cancer patients receiving bevacizumab-containing therapies