Category Archives: Cancer medicine (Oncology)

There has been much written about the rather minor improvement in breast cancer outcomes with Avastin (bevacizumab).  My last post pointed out one theoretical problem with use of this drug in cancer.

In this week’s NEJM there  are two studies, reporting a small beneficial effect with bevacizumab in patients with early HER2-negative breast cancer.  The authors of one study  note:  (other study here)

The addition of bevacizumab to neoadjuvant chemotherapy significantly increased the rate of pathological complete response among patients with HER2-negative early-stage breast cancer. Efficacy was restricted primarily to patients with triple-negative tumors, in whom the pathological complete response is considered to be a reliable predictor of long-term outcome.

In the study 1948 newly diagnosed breast cancer patients were randomized to receive chemotherapy alone or with concomitant bevacizumab before surgery (neoadjuvant treatment).  The results showed that pathological complete response  was 18.4% in patients receiving bevacizumab and 14.9% without it.  A difference of 3.5%, hardly significant.  In patients with triple negative tumors (ER, PR and HER2 negative) the results were more impressive with 27.9% pathologic complete remission without bevacizumab and 39.3%   with it.  There was no difference in the 1262 ER PR positive patients.  (7.8 and 7.7%)

We don’t know at this time whether the improved CR rate in these patients will translate into improved survival and hopefully cures.

Medicynical Note:  What we can determine however is the cost of the intervention.  Consider the 663 patients that were triple negative.  I assume that about half (I don’t have full access to the article), let’s say 330 patients received bevacizumab.  Then lets take the 39.3% complete response rate,11.6% more than those not receiving the drug, and do a rough estimate of cost. 

39.3% of 330 is 129.69 patients achieved complete remission.  11.6% or 38.38 patients was the incremental benefit.  Assuming a cost in the range of $50,000 for a 3-5 month course of treatment, the total cost of treating these 330 patients with the best outcome in the study would be (paying market prices for the drug) in the range of 16 and a half million dollars.  Dividing that by the incremental benefit of 38.38 the cost of the benefit/patient  was $429,911.

Cost is a real problem for a health care non-system that spends 17% of GDP on health care,  almost twice that of other countries.  Can we afford an intervention that costs over $400,000/patient who benefits?  

I have no particular bias against Avastin (bevacizumab) except for the fact that it (and other similar drugs) appears to have very limited efficacy and is so expensive.  If it were a drug costing $5000-10,000 for a course of treatment I’d say give it a try.  At the present cost and level of efficacy it’s hard to find a strong argument for it’s use, except that it must make the manufacturers and their stockholder a great deal of profit.

There is wide documentation of the relative ineffectiveness of Avastin (bevacizumab) in breast cancer.  The drug simply doesn’t extend the lives of those treated significantly. 

Why?  It ‘s been an open question with the drug company maintaining that the drug costing between $75,000 and $120,000/year for treatments has some effect and that is enough to warrant it’s continued use.  The FDA differed and removed the breast cancer indication, though some insurers for some some reason continue to pay.

There is now an explanation why the drug failed.

Antiangiogenic therapy has been thought to hold significant potential for the treatment of cancer. However, the efficacy of such treatments, especially in breast cancer patients, has been called into question, as recent clinical trials reveal only limited effectiveness of antiangiogenic agents in prolonging patient survival. New research using preclinical models further suggests that antiangiogenic agents actually increase invasive and metastatic properties of breast cancer cells. We demonstrate that by generating intratumoral hypoxia in human breast cancer xenograpfts, the antiangiogenic agents sunitinib and bevacizumab increase the population of cancer stem cells. 

If the finding is confirmed it provides an explanation of the mediocre results in breast and other cancers for this drug.  It raises question about it’s continued use and certainly would argue against using it alone either as a primary treatment or maintenance therapy option.

Medicynical Note:  One hopes this is new information and that the drug company was not previously aware of the increase population of stems cell generated by presumed antiangiogenic caused hypoxia. 

More broadly, how can it be that our pharmaceutical industry sells drugs (sometimes even effective drugs) at twice the median and average income of citizens.  This is not a sustainable model either for business or for health care.

There’s obviously something wrong with our drug development system; drug patents: our non-system of health care; and our payment schemes.  If we ultimately want to reform health care these issues need to be addressed.

It’s remarkable how drug companies spin the limited proven benefits of their new drugs.   This in the LA Times:

Avastin can stabilize tumors in ovarian cancer, studies find

Two independent groups working with advanced-stage cases say the drug extended the period before the disease worsened by more than 3.5 months.

At this point there is little data indicating that people with ovarian cancer treated with Avastin (bevacizumab) live longer. 

Medicynical Note:  In the past the end points for a cancer treatment advance was actual proof of shrinkage of tumor masses and a significant survival benefit.  In recent years companies have tried to sell “delay in progression” as proof of benefit.  Often as not however, this “delay”, when found, is not repeatable on follow-up trials and/or there was no observed survival benefit.    That was the case when the FDA deauthorized this same drug’s use in breast cancer because the short delay in progression was not replicated and did not increase breast cancer patients’ length of life.

The problems with Avastin are it’s outrageous price, in the range of $100,000/year and the apparent fact that it is only marginally effective.  This type drug is marketed to desperate patients with life threatening illness and priced way out of proportion to it’s benefit, or even development costs.  It is a fact that most of the early development costs came not from drug companies but rather from taxpayers in the form of research grants.

At a cost to consumers and insurers of nearly $100,000/year, more than practically any other consumer purchase, and just a few months delay in progression–Would you buy a $100,000 car that lasted 3.5 months?–it’s hard to be enthusiastic .