FDA finds Avastin doesn't extend lives in BC patients... ?

[gdpawel]

Published online 21 November 2010 | Nature | doi:10.1038/news.2010.623

http://www.nature.com/news/2010/1011....2010.623.html

About the most key statement in the article (when it comes to treatment) is, "most people agree that a single pathway is not going to do it." When you get rid of VEGF with Avastin, the body cranks out other types of blood vessel growth/survival factors.

The problem with Avastin is the same thing that was a problem with AZT for HIV/AIDS. Early results, then rapid resistance. Solution was combination therapy to attack different targets. With cancer, it's going to take combination antivascular therapy to make a difference.

Tumor vasculature needs VEGF to survive. Avastin removes VEGF, killing blood vessels. But other proangiogenic factors can substitute: FGF, PDGF, ephrin A1, angioprotein 1, IL-8 etc. We need to attack these other targets, as well.

If you can achieve this, then you may not even need the other drugs, which don't get into the tumor so well. But angiogenic attack provides true selective toxicity, something which is sorely lacking with all of the other treatments.

Perhaps Avastin "sensitive" tumors secrete relatively low levels of VEGF. Tumors which secrete relatively low levels of VEGF might be more susceptible to an agent which works by blocking VEGF.

As the article mentions "vascular mimicry," something I've written about on the board previously, there are multiple ways by which tumors can evolve that are independent of VEGF and independent of angiogenesis.

Tumors can acquire a blood supply by angiogenesis, co-option of existing blood vessels and vasculogenic mimicry. All must be inhibited to consistently starve tumors of oxygen.

While vasculogenic mimicry - some types of cancers form channels that carry blood, but are not actual blood vessels - with co-option, instead of growing new blood vessels, tumor cells can just grow along existing blood vessels. This process cannot be stopped with drugs that inhibit new blood vessel formation.

The consistent and specific cure or control of cancer will require developing and using a set of drugs, given in combination, targeted to patterns of normal cellular machinery related to proliferation and invasiveness.

A sufficient number of independent methods of cell killing must be employed so that it is too improbable for a cancer cell to evolve that can escape death or inactivation. It must examine every cell in the body and must do so for a prolonged period of time.

Given the current state of the art, cell-based in vitro drug sensitivity testing (with functional profiling) could be of significant clinical value. One aspect of a functional profiling assay is that microvascular viability can measure dead microvascular cells in tissue, fluid and peripheral blood specimens to identify potential responders to anti-angiogenic drugs (Avastin, Nexavar, Sutent) and to assess direct and potentiating anti-angiogenic effects of tyrosine kinase targeted therapy drugs (Tarceva, Iressa).

[gdpawel]

The UK’s National Institute for Health and Clinical Excellence has rejected the use of Roche’s Avastin for treating breast cancer on the grounds that the med offers “limited and uncertain benefit” for patients compared with existing treatments. Roche had calcuated the total average cost of treating a patient with Avastin plus chemotherapy is more than $52,000.

“Unfortunately, we did not receive any evidence from the manufacturer to show that (Avastin) can significantly lengthen a patient’s life or, importantly, offer a better quality of life than existing treatments. Although the data seemed to show that the drug may slow the growth and spread of the cancer, the size of this effect varied between studies. Furthermore, it was extremely unclear that the benefits in terms of slowing tumour growth translated into benefits on overall survival, which is what really matters for patients,” NICE chief executive Andrew Dillon says in a statement.

Nonetheless, the decision casts an ominous shadow over an upcoming decision by the FDA. Last July, you may recall, an FDA advisory committee dealt Roche a blow by voting 12 to 1 to recommend the agency withdraw approval for the multibillion-dollar cancer drug for treating breast cancer. The FDA approved Avastin two years ago to fight breast cancer, but two studies - which were undertaken as a condition of approval - found patients given Avastin and chemotherpay didn’t survive longer than those given chemo alone. Avastin patients also suffered more serious side effects.

The Avastin decision has stirred controversy over the yardsticks used to approve Avastin for breast cancer treatment and the FDA’s accelerated approval program. For instance, one advocacy group, Breast Cancer Action, maintains the FDA placed too much emphasis on surrogate markers, specifically, progression-free survival. Meanwhile, some cancer patients worry the agency will yank the med, which in some cases has been proven helfpul.

Source: Pharmalot

http://www.nice.org.uk/newsroom/pres...eastCancer.jsp

http://www.pharmalot.com/2010/07/fda...breast-cancer/