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October 6, 2024
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Zaltrap and the High Cost of Chemotherapy Drugs

I don’t think I have to explain in these pages how difficult it is to find a drug that can be effective as a chemotherapeutic agent. For any given cancer site, the list of effective drugs, despite the widespread and aggressive testing and efforts to screen and test hundreds of agents, is disappointingly small.

Thus, when one has the rare success of an FDA approval of a drug for use for a cancer site, that should be an occasion for rejoicing and immediate utilization of the new drug to the extent possible. Colorectal cancer for many years had only one effective drug, 5-fluorouracil, but after 1998, several other drugs were also found to be effective in its treatment. Nonetheless, it never hurts to have one more.

Zaltrap (aflibercept) is a vascular endothelial growth factor (VEGF) inhibitor developed by a major pharmaceutical company, Regeneron, for use in treating macular degeneration, a serious ophthalmologic condition. Growing tumors need increased blood flow of nutrients and oxygen and thus they require the proliferation and development of new blood vessels; VEGF inhibitors interfere with this and thereby block tumor growth and so Zaltrap was tested for use in cancer starting in 2001. Ultimately a randomized trial published in 2011 demonstrated that its addition to a second-line treatment regimen could prolong survival for patients with metastatic colorectal cancer by an average of about two months, a respectable benefit. Along with other results from other trials, and a good toxicity profile, it received approval from the FDA in 2012 to be marketed for the treatment of advanced colorectal cancer.

At the time it was approved, there was already a VEGF inhibitor on the market that was in widespread use, Avastin (bevacizumab), produced by Genentech. Zaltrap had no particular benefit in efficacy over bevacizumab, and its toxicity profile was similar. The FDA, when evaluating drugs for approval, does not consider their comparative efficacy to existing drugs, nor does it take into account cost.

At the time of approval, treatment with Zaltrap was planned to run about $11,000/month ($130,000 per year) while bevacizumab was costing about $5,000/month. So why would an oncologist choose to utilize Zaltrap in preference to the use of bevacizumab? It could be simply novelty—it is always interesting or tempting to try out a new drug or procedure. There could be other reasons as well, including intensive marketing by the pharmaceutical company.

Such billing choices are commonplace in medicine, oncology or otherwise, and a profit motive is not a sin (I don’t exempt myself). However, for some reason (I confess that I do not know why to this day), the Zaltrap-bevacizumab cost discrepancy triggered a more profound reaction than had occurred previously. In other words, this was not the first time a new, expensive drug or intervention had entered the medical marketplace and, in most cases, everyone just went with the flow and accepted the new price schema. This time was different.

On October 14, 2012, three physicians from Memorial Sloan-Kettering—Drs. Peter Bach, Leonard Saltz and Robert Wittes published an op-ed piece in The New York Times declaring that their cancer center would refuse to add Zaltrap to the hospital’s pharmacopeia, and they would not make it available to their patients for advanced cancer. This was a very unusual and relatively bold move, perhaps unprecedented, to refuse a drug based on cost. This decision apparently followed significant internal debates at Memorial. (The reader will hopefully forgive a Columbia faculty member’s cynicism if I opine that there was probably no senior administrative or academic officer at Memorial who was on the board of directors at Sanofi or Regeneron, the companies producing Zaltrap at this point in time, or this bold move would likely have been stopped dead in its tracks.)

As it was, the effect of this declaration was stunning. A week later, Sanofi/Regeneron cut the price of the drug in half. But the damage was already done. Most oncologists never started to use the drug, including the group at my own hospital. The drug never made it big in the U.S. and it has mostly faded into the woodwork.

So having had this incredible success at price containment, what drug did these physicians go after next? I can reliably assert that the potential list of new drugs with incredible prices is long. Well, I suppose there was at least some effort in the ensuing months/years by the industry to appear at least a bit more controlled in their pricing. But the truth is that this action was not repeated again to my knowledge. I assume that Memorial faculty members are on the boards of most companies. And oncology drug prices continue to amaze and affront and to bear little or no relationship to efficacy.


Alfred I. Neugut, MD, PhD, is a medical oncologist and cancer epidemiologist at Columbia University Irving Medical Center/New York Presbyterian and Mailman School of Public Health in New York.

This article is for educational purposes only and is not intended to be a substitute for professional medical advice, diagnosis, or treatment, and does not constitute medical or other professional advice. Always seek the advice of your qualified health provider with any questions you may have regarding a medical condition or treatment.

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