New York Times Examines Benefits, Costs Of Cancer Drug Avastin
Main Category: Cancer / OncologyAlso Included In: Colorectal Cancer; Lung Cancer; Breast Cancer
Article Date: 08 Jul 2008 - 12:00 PDT
The New York Times on Sunday examined how the Genentech cancer drug Avastin "signifies both the hopes and dilemmas of modern medicine" because while it offers incremental benefits for cancer patients, the drug is costly and concerns have been raised about its safety and efficacy. The drug, which is seen as a "wonder drug" for its ability to cut off blood supply to tumors, costs as much as $100,000 annually and had sales of $3.5 billion last year. Research shows that the drug prolongs the lives of patients with colon, lung or breast cancer by "only a few months, if that," and some recent studies suggest that it could be less effective than FDA believed it to be when approving the drug, the Times reports. Some patients and physicians say Avastin improves the quality of life, allowing patients to perform daily functions without exhaustion, but such benefits are difficult to confirm, according to the Times.
Side effects for the drug are "serious, if infrequent," and can be lethal, according to the Times. Studies have shown that the drug is more effective when used with standard chemotherapy, so "patients on Avastin do not escape chemotherapy's side effects," according to the Times. In addition, patients with cancers other than colon, lung or breast are often given the drug, even in cases where there is not "compelling evidence that it can help," according to the Times. "I still use Avastin routinely, but it's sobering," Leonard Saltz, a colon cancer specialist at Memorial Sloan-Kettering Cancer Center, said. He added, "It's not a small dunk, and in fact, the incremental benefit may be more modest than we want to admit."
Some "in the pharmaceutical industry worry" that high prices "will raise concerns about whether the drug is worth it," potentially causing "backlash like price controls or restrictions on use," the Times reports. Roy Vagelos, a former CEO of Merck, said, "There is a shocking disparity between value and price, and it's not sustainable." Medicare reimburses physicians prescribing Avastin at an amount equal to Genentech's average selling price -- which is between $4,000 and $9,000 per month -- plus a markup of 5% to 6%. Medicare pays 80% of the cost of the drug and beneficiaries pay the remaining 20%. Private insurers "sometimes pay several times as much as Medicare" for the drug because physicians and hospitals at times have charged up to $35,000 per month for Avastin and insurers' contracts require them to cover a certain percentage of the cost.
Avastin is being formally tested in up to 450 clinical trials for about 30 types of cancer. Genentech and its partner Roche, as well as the National Cancer Institute are beginning studies involving more than 26,000 people with colon, lung and breast cancer at earlier stages of the disease than were previously studied. If the drug is found effective in delaying the return of cancer in these groups and it is approved by FDA, Avastin could be prescribed to hundreds or thousands of additional people, which experts say could "impose a considerable financial burden," the Times reports (Kolata/Pollack, New York Times, 7/6).
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The True Costs And Benefits Of Avastin
posted by Gregory D. Pawelski on 8 Jul 2008 at 3:45 pmWhat may limit the effectiveness of Avastin is that 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 three different mechanisms: angiogenesis; co-option of existing blood vessels; and vasculogenic mimicry. All must be inhibited to consistently starve tumors of oxygen.
Instead of growing new blood vessels, tumor cells can just grow along existing blood vessels. This process, called co-option, cannot be stopped with drugs that inhibit new blood vessel formation. Some types of cancers form channels that carry blood, but are not actual blood vessels. Drugs that target new blood vessel formation also cannot stop this process, called vasculogeneic mimicry. The realization is that starving tumors by shutting off their blood flow requires that all three mechanisms be addressed.
It could be vastly more important to measure the net effect of all processes (systems) instead of just individual molecular targets (like VEGF). The cell is a system, an integrated, interacting network of genes, proteins and other cellular constituents that produce functions. You need to analyze the systems' response to drug treatments, not just one or a few targets or pathways.
There are many pathways to the altered cellular (forest) function, hence all the different "trees" which correlate in different situations. Improvement can be made by measuring what happens at the end (the effects on the forest), rather than the status of the indiviudal trees.
VEGF-targeted drugs are poorly-predicted by measuring the preferred target VEGFR. They can be well-predicted by measuring the effect of the drug on the function of live cells.
Many of these fine drugs (and Avastin is a miracle drug for the few) cry out for validated clinical biomarkers as pharmacodynamic endpoints and with the ability to measure multiple parameters in cellular screens to help set dosage and select people likely to respond. Many molecular diagnostics approved often have been mostly or totally ineffective at identifying clinical responders to various therapies.
If you find one or more implicated proteins in a patient’s tumor cells, how do you know if they are functional (is the encoded protein actually produced)? If the protein is produced, is it functional? If the protein is functional, how is it interacting with other functional proteins in the cell?
All cells exist in a state of dynamic tension in which several internal and external forces work with and against each other. Just detecting an amplified or deleted gene won’t tell you anything about protein interactions. Are you sure that you’ve identified every single protein that might influence sensitivity or resistance to a certain class of drug?
Assuming you resolve all of the preceeding issues, you’ll never be able to distinguish between susceptibility of the cell to different drugs in the same class. Nor can you tell anything about susceptibility to drug combinations. And what about external facts such as drug uptake into the cell? You're not going to accomplish this using genetic tests.
Improving cancer patient diagnosis and treatment through a combination of cellular and gene-based testing will offer predictive insight into the nature of an individual's particular cancer and enable oncologists to prescribe treatment more in keeping with the heterogeneity of the disease. The biologies are very different and the response to given drugs is very different.
The major obstacle in controlling cancer drug prices is the widespread inappropriate use of anti-cancer drugs. As the increasing numbers and types of anti-cancer drugs are developed, oncologists become more and more likely to misuse them in their practice. There is seldom a "standard" therapy which has been proven to be superior to any other therapy. What may work for one, may not work for another.
Literature Citation:
Eur J Clin Invest 37 (suppl. 1):60, 2007
Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings Part I. Vol 24, No. 18S (June 20 Supplement), 2006: 17117
"Cure: Scientific, Social, and Organizational Requirements for the Specific Cure of Cancer" A. Glazier, et al. 2005
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