HER2 Support Group Forums - View Single Post - Finally a Way to Predict Bevacizumab Response?

gdpawel · 07-04-2013, 10:05 AM

Bevacizumab has its own activity, usually in combination with cytotoxic in many neoplasia (breast, kidney, ovarian, colorectal cancer).

The impact is most often measured by a small but significant gain in DFS with heterogeneity in cancer and between populations.

However, the lack of biological factors identified for the response, a non-anecdotal toxicity profile, and the high cost of the product, led U.S. regulators to revoke its use in cancer metastatic breast, pending further data, including biological type.

Bevacizumab is not, strictly speaking, a targeted therapy, since its action and target are relatively ubiquitous. However, it should be possible to identify biomarkers of efficacy. Thus the authors of this beautiful literature review suggest all tracks being followed.

The main target of bevacizumab is the theory circulating VEGF-A. Many other factors involved in angiogenesis and stimulation of pericytes potentially involved in the mechanism (IGF, FGF, etc. ..).

Regarding circulating factors, it identifies 17 randomized studies have studied how the correlation between the ancillary level of expression of certain biomarkers with efficacy parameters (DFS or OS). It follows from this that the short isoform of VEGF-A is the candidate most "sharp" to predict the DFS expression of neuropilin-1, and the expression of VEGF receptor-1 in plasma and tumor are also good candidates.

Similarly, several studies have identified changes in the rate of VEGF-A and PlGF as a predictor of response.

In the tumor environment, the study of VEGR1 markers and NRP1 was not real contribution, but remains an interesting way.

Genetic variants of VEGF-A are also avenues to explore. Indeed, more than a dozen variants have been identified as correlated with PFS in twenty studies.

Regarding tumor subtypes in breast cancer, studies AVADO, BEATRICE and AVEREL failed to 'actually identify a correlation.

In colon cancer, genomic status of KRAS and BRAF does not appear to be related to efficiency.

A first study has been ongoing since 2012 in metastatic breast cancer, named Meridian with stratification based on the expression level of the short isoform of VEGF-A. This is really the first study based its main hypothesis on the relationship between biomarker and efficacy.

I bet that a number of studies done on this concept will be created, which is not necessarily obvious in the priorities of development time and the high cost of this type of study on a scale Phase III.

David Coeffic, Editor France Cancer

Reference: Lambrechts D, Lenz HJ, Haas S, et al. Markers of response for the antiangiogenic agent bevacizumab. J Clin Oncol. 20 March 2013, 31 (9) :1219-30.

07-04-2013, 10:05 AM	#2
gdpawel Senior Member Join Date: Aug 2006 Location: Pennsylvania Posts: 1,080	French interpretation of this Bevacizumab has its own activity, usually in combination with cytotoxic in many neoplasia (breast, kidney, ovarian, colorectal cancer). The impact is most often measured by a small but significant gain in DFS with heterogeneity in cancer and between populations. However, the lack of biological factors identified for the response, a non-anecdotal toxicity profile, and the high cost of the product, led U.S. regulators to revoke its use in cancer metastatic breast, pending further data, including biological type. Bevacizumab is not, strictly speaking, a targeted therapy, since its action and target are relatively ubiquitous. However, it should be possible to identify biomarkers of efficacy. Thus the authors of this beautiful literature review suggest all tracks being followed. The main target of bevacizumab is the theory circulating VEGF-A. Many other factors involved in angiogenesis and stimulation of pericytes potentially involved in the mechanism (IGF, FGF, etc. ..). Regarding circulating factors, it identifies 17 randomized studies have studied how the correlation between the ancillary level of expression of certain biomarkers with efficacy parameters (DFS or OS). It follows from this that the short isoform of VEGF-A is the candidate most "sharp" to predict the DFS expression of neuropilin-1, and the expression of VEGF receptor-1 in plasma and tumor are also good candidates. Similarly, several studies have identified changes in the rate of VEGF-A and PlGF as a predictor of response. In the tumor environment, the study of VEGR1 markers and NRP1 was not real contribution, but remains an interesting way. Genetic variants of VEGF-A are also avenues to explore. Indeed, more than a dozen variants have been identified as correlated with PFS in twenty studies. Regarding tumor subtypes in breast cancer, studies AVADO, BEATRICE and AVEREL failed to 'actually identify a correlation. In colon cancer, genomic status of KRAS and BRAF does not appear to be related to efficiency. A first study has been ongoing since 2012 in metastatic breast cancer, named Meridian with stratification based on the expression level of the short isoform of VEGF-A. This is really the first study based its main hypothesis on the relationship between biomarker and efficacy. I bet that a number of studies done on this concept will be created, which is not necessarily obvious in the priorities of development time and the high cost of this type of study on a scale Phase III. David Coeffic, Editor France Cancer Reference: Lambrechts D, Lenz HJ, Haas S, et al. Markers of response for the antiangiogenic agent bevacizumab. J Clin Oncol. 20 March 2013, 31 (9) :1219-30.