Category Archives: Cancer medicine (Oncology)

Avastin (bevacizumab): Fails Older Lung Cancer Patients

Another study of bevacizumab (Avastin), this time in lung cancer, showing minimal to no improvement in outcomes with treatment.  Remember this drug costs in the range of $80-100,000/year.

In a study being published this week in the Journal of the American Medical Association, those treated with bevacizumab and chemotherapy did not live significantly longer than those simply treated with chemo.

Patients aged 65 and older who received Avastin in addition to a standard chemotherapy regimen had a median overall survival of 9.7 months, according to the study to be published tomorrow in the Journal of the American Medical Association. While that was longer than the 8.9 months and 8 months for two groups of patients receiving chemotherapy only, the finding wasn’t statistically significant, said the researchers from the Dana- Farber Cancer Institute in Boston.

Avastin, a $5.8 billion-a-year product also known as bevacizumab, won U.S. Food and Drug Administration approval for non-small cell lung cancer in 2006, after a study found the therapy improved survival by a median of two months. That research showed no benefit among patients aged 65 and older, who are covered by Medicare, the government health-insurance program for the elderly and disabled. At least two-thirds of patients with lung cancer qualify for Medicare, which has covered Avastin for that use since FDA approval, the authors said.

And:

Patients in the Avastin group had a 39.6 percent probability of surviving one year, compared with 40.1 percent getting chemotherapy from 2006-2007 and 35.6 percent for those treated earlier than 2006, the study found. More recent data might yield different results, the researchers said

Medicynical Note:  Roche may dispute the findings but what is clear is that bevacizumab (Avastin) has a minimal if any beneficial effect in elderly lung cancer patients.

This drug brings in 5.8 billion dollars in revenue to Roche, about the same amount as the cost of malpractice litigation in the U.S. (See previous Medicynic for details)  We’re talking big bucks for a drug with limited benefit. 

We have a non-system of care that costs too much.   Drugs such as bevacizumab (Avastin) are part of the problem.

More here

Bevacizumab should not be considered part of the “backbone” of treatment or the standard of care for older patients with advanced disease, said lead author Deborah Schrag, MD, MPH, from the Dana-Farber Cancer Institute in Boston, Massachusetts. She spoke at a press conference, held in Washington, DC, on the journal’s new issue, which centers on comparative effectiveness research.

Cancer Survival Study: Exaggerated and Misleading

A recent study being published in Health Affairs written by a fellow of the conservative American Enterprise  Institute and Manhattan Institute and funded by Bristol Meyers Squibb is being criticized as misleading and poorly done.

The study notes:

Cancer patients in the United States who were diagnosed from 1995 to 1999 lived an average 11.1 years after that, compared with 9.3 years for those in 10 countries in Europe, researchers led by health economist Tomas Philipson of the University of Chicago reported in an analysis published Monday in the journal Health Affairs.

Those extra years came at a price. By 1999 (the last year the researchers analyzed), the United States was spending an average of $70,000 per cancer case (up 49 percent since 1983), compared with $44,000 in Europe (up 16 percent). Using standard figures for an extra year of life, the researchers concluded that the value of the U.S. survival gains outweighed the cost by an average $61,000 per case. The greater spending on cancer care in the United States, they conclude, is therefore “worth it.”

But critics believe:

“This study is pure folly,” said biostatistician Dr. Don Berry of MD Anderson Cancer Center in Houston. “It’s completely misguided and it’s dangerous. Not only are the authors’ analyses flawed but their conclusions are also wrong.”

The heart of the problem is that the authors naively forgot about lead time bias and effect of earlier diagnosis of often times benign behaving tumors that would never cause a patient problems.  Since the U.S. has a more aggressive disease screening program and diagnoses more of these benign growths their patients appear to survive longer but the improved survival has nothing to do with treatment benefit.

As the critics note:

If a tumor is diagnosed very early in its existence – if it has a long “lead time” – the patient may survive, say, two years if the tumor is very aggressive. If an identical tumor is found in that patient’s identical twin later, the twin will survive, say, six months. But the twins die at the same age. The first survived longer with cancer due to lead-time bias, but did not have a longer lifetime.

Crediting medical care with “improving survival” is therefore misleading, cancer experts have long argued. Lead-time bias makes it seem patients live longer, but the only thing that is longer is the number of years they know they have cancer, not their lifespan.

Read the rest of the article to learn more of the flaws of this dangerous biased study.

Medicynical note:  It is not an accident that this study is drug company sponsored and that the results overstate the benefit of treatment.  While there has been some progress in decreasing cancer mortality  it comes mostly from prevention (smoking cessation) and earlier diagnosis. 

What’s most interesting is the amount of money the authors propose as reasonable to spend to extend a person’s live one year—$150,000 to $360,000.  As Ewe Reinhardt notes:

“Are American taxpayers willing to pay $150,000 in added taxes (Medicyncial addition: and insurance premiums) to purchase an added life year for some poor person?” asked health economist Uwe Reinhardt of Princeton University. “Does the urge to cut government spending on Medicare and Medicaid suggest Congress is willing to purchase added life years for anyone who cannot purchase it with his or her own money at a price of $150,000 per year?”

Rather than try and justify our exceptionally expensive and inefficient health care non-system we should be working to find what works best and is the most cost efficient. 

Our problem with health care in the U.S. is that we can’t afford the non-system that we have created.  It’s a monster that’s eating us alive.

Neglected Cancers–A Common Problem in the U.S.

I go to tumor board at our local hospital.  Approximately once a month we encounter patients who delayed diagnosis and treatment because of lack of funds and insurance.  It’s the American way of care.

Consider this:  

The patient in the emergency department smelled of advanced cancer. It is the smell of rotting flesh, but even more pungent. You only ever have to smell it once.

She had been bleeding irregularly, but chalked it up to “the change.” Peri-menopausal hormonal mayhem is the most common cause of irregular vaginal bleeding, but unfortunately not the only cause.

She hadn’t gone to the doctor because she had no health insurance. The only kind of work she could get in a struggling rural community was without benefits. Her coat and shoes beside the gurney were worn and her purse from another decade. She could never afford to buy it on her own. She didn’t qualify for Medicaid, the local doctor only took insurance, and there was no Planned Parenthood or County Clinic nearby.

Medicynical Note:  The opponents of health care often point out that people sooner or later can get care in our non-system.  The problem is the later part. 

This woman at one time had curable disease. 

Entering La La Land— Cancer Drug Costs Abirateron (Zytiga) vs Sipuleucel-T (Dendreon)

The recent approval of abirateron by the FDA for use in metastatic prostate cancer highlights the otherworldly practice of cancer drug pricing. 

Sipuleucel-T purported to be an immune stimulator in early trials was reported last year to improve survival of patients with metastatic prostate cancer about 4 months  (median) when compared with placebo.  Similarly the recently approved abirateron shows a 2 months delay in progression, 3.9 months improvement of median survival.

Sipuleucel-T (Dendreon) you will recall is priced at $97,000 for a course of therapy.  The new drug abirateron is a relative “bargain” at $5,000/month.

The industry’s view is that this is a “fair” price.  Meaning it is competitive and will earn the company money:

The pharmacy strategy blog notes:

  This gives a treatment price of ~ $40K, which I think is very fair, although some patients will obviously take it for longer than that.

In U.K. however NICE (National Institute for Health and Clinical Excellence) notes:

In draft guidance the watchdog said that Zytiga could increase survival by more than three months compared to placebo, but its annual cost of £35,160 was too much for the NHS in England.

Janssen has offered a patient access scheme for the drug that would discount its list price, but NICE said even with this in place, the drug was still not cost effective.

NICE suggests that conventional chemotherapy offers a more cost effective approach.

Medicynical Note:  Welcome to the alternative universe of drug pricing in the U.S.  This is the only situation where a consumer purchases a product costing many many thousands of dollars that has utility (effectiveness) of 4 months or less.  It’s like buying a Mercedes or Porsche that will last 4 months—rational people in rational situations wouldn’t buy such a product. 

Cancer patients however are desperate.  Drug companies price these drugs to take advantage.  Patient care?  Cost efficiency? Morality?  Not their department. 

I do look forward to further studies of these new agents and hope that the results are confirmed.  However, I would warn readers that the track record of drug sponsored first studies is that they often exaggerate benefits and minimize toxicity. 

Death from Vascular Endothelial Growth TKI Inhibitors — pazopanib, sunitinib, and sorafenib

A recently published study on pazopanib, sunitinib, and sorafenib reported an increase in “fatal adverse events”, death.

In all, 4,679 patients from 10 randomized controlled trials (RCTs) were included, with 2,856 from sorafenib, 1,388 from sunitinib, and 435 from pazopanib trials. The incidence of FAEs related to VEGFR TKIs (Tyrosine Kinase Inhibitors) was 1.5% (95% CI, 0.8% to 2.4%) with an RR of 2.23 (95% CI, 1.12 to 4.44; P ? .023)
compared with control patients. On subgroup analysis, no difference in the rate of FAEs was found between different VEGFR TKIs or tumor types. No evidence of publication bias was observed.

The risk of dying while on these drugs was over twice that of those treated with a placebo. 

Medicynic:  These are marginally active drugs, improving outcomes by a few months.  Whatever benefit they have is partially compromised by these excess deaths.

Avastin (bevacizumab) works on vascular endothelial growth factor in a different way.  But it too has toxicity and may also have a small excess mortality.

Sobering study. No treatment, even expensive targeted treatments with “fewer side-effects,”  are without problems.

Semulaparin: Effective Maybe, Cost Effective?

It’s difficult to assess the cost effectiveness of a new intervention when price data is unavailable.  That’s the case with semulaparin, a new anticoagulant that is not FDA approved.

The NEJM this week reports that using semulaparin decreases the incidence of blood clots in cancer patients.

Venous thromboembolism occurred in 20 of 1608 patients (1.2%) receiving semuloparin, as compared with 55 of 1604 (3.4%) receiving placebo (hazard ratio, 0.36; 95% confidence interval [CI], 0.21 to 0.60; P<0.001), with consistent efficacy among subgroups defined according to the origin and stage of cancer and the baseline risk of venous thromboembolism.

There was a slight increase in bleeding complications in the semulaparin group 2.8% vs 2% in the placebo group.

The authors conclude that the drug reduces the incidence of thromboembolism in patient on chemotherapy.

Sanofi’s press release touted the results as well:

Sanofi (EURONEXT: SAN and NYSE: SNY) announced today results of the pivotal SAVE-ONCO study which demonstrated that, in cancer patients initiating a chemotherapy regimen, investigational semuloparin significantly  reduced the risk of the composite of symptomatic-deep vein thromboembolism (DVT), non-fatal pulmonary embolism (PE) or venous thromboembolism (VTE)-related death by 64%[]i], meeting the study primary endpoint (respectively 1.2% and 3.4% for semuloparin and placebo HR 0.36 95% CI (0.21-0.60)), p< 0.0001).

Medicynical Note:  The daily costs of the currently available low molecular weight heparins are between $35 and $80 dollars/day.  Assuming self-injection and negligible cost for other materials. 

The mean duration of the treatment regimens in the NEJM study was 3.5 months (approximately 100 days).  $35/day for 100 days and 80/day for 100 days gives a treatment cost for patient of between $3500 and $8000/patient.

1608 patients were treated in the study.  Using this number and the estimated cost/day, providing a low weight molecular heparin to these patients would be between $5,628,000 million dollars if the drug costs $35/day and $12,864,000 at $80/day.

The benefit noted in the article was a difference of 35 occurrences of venous thrombo-embolism between the placebo and treated group.  This gives a cost range of between $160,000 and $367,542 per thrombo-embolus prevented.

Cost effective?  Probably not.

More on Avastin (bevacizumab) in Breast Cancer– $400,000/patient

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.