Category Archives: Cancer medicine (Oncology)

Prostate Cancer Radiation: Proton beam costs twice as much, twice as good? NO

A recent retrospective study looked at outcomes in prostate cancer treated with Proton radiotherapy (PRT)  vs intensity-modulated radiotherapy (IMRT).

And the results:

We identified 27,647 men; 553 (2%) received PRT and 27,094 (98%) received IMRT. Patients receiving PRT were younger, healthier, and from more affluent areas than patients receiving IMRT. Median Medicare reimbursement was $32,428 for PRT and $18,575 for IMRT. Although PRT was associated with a statistically significant reduction in genitourinary toxicity at 6 months compared with IMRT (5.9% vs 9.5%; odds ratio [OR] = 0.60, 95% confidence interval [CI] = 0.38 to 0.96, P = .03), at 12 months post-treatment there was no difference in genitourinary toxicity (18.8% vs 17.5%; OR = 1.08, 95% CI = 0.76 to 1.54, P = .66). There was no statistically significant difference in gastrointestinal or other toxicity at 6 months or 12 months post-treatment.

Medicynical Note:  There is a build it and they will come mentality in medicine that applies to new approaches that are costly and have little benefit.  In this case Proton Beam radiotherapy has a word of mouth that it is less “toxic”,  fostered in part by institutions that invested in this prohibitively expensive equipment. 

It appears, however, that the benefits of this modality are overstated, as often is the case with medical “advances,” and that the nearly 100% additional expense of proton beam treatment  is not justified in prostate cancer.

And When a Medicine (Revlimid) “Works” It’s Unaffordable: $132,000/year, $534/pill

Poignant piece in the NY Times magazine that highlights some of the flaws in our unsustainable health care non-system.  This paragraph outlines the problem

After making more than 70 phone calls to 16 organizations over the past few weeks, I’m still not totally sure what I will owe for my Revlimid, a derivative of thalidomide that is keeping my multiple myeloma in check. The drug is extremely expensive — about $11,000 retail for a four-week supply, $132,000 a year, $524 a pill. Time Warner, my former employer, has covered me for years under its Supplementary Medicare Program, a plan for retirees that included a special Writers Guild benefit capping my out-of-pocket prescription costs at $1,000 a year. That out-of-pocket limit is scheduled to expire on Jan. 1. So what will my Revlimid cost me next year?

Medicynical note:  Anyone believing our non-system is the best in the world should need such drugs.  While  drug companies  spend a great deal to develop medications,  their costs are inflated and overstated.  Efficiency is simply not on their agenda.  Nor is patient well being, access or for that matter outcomes. 

It’s the money stupid!  Charging more than twice the median U.S. income for a single drug that patients in life-threatening situation, any single drug,  is simple blackmail.  It reflects an industry and economy gone mad.

Cabozantinib: A Miracle Cancer Drug without Survival Benefit

The FDA recently approved cabozantinib for use in medullary carcinoma.  What’s noteworthy about this drug is that it will likely be very expensive and that it does not, repeat does not improve the patients survival. 

Read the following for an extremely biased assessment of the drug’s efficacy: (likely from the drug companies PR info)

Below are some data showing Cometriq’s superiority over placebo:

  • Those on Cometriq survived 11.2 months (average) with no tumor growth
  • Patients in the placebo group survived 4 months (average) with no tumor growth
  • 27% of those in the placebo group experienced tumor reductions which lasted an average of almost 15 months
  • None of the participants in the placebo group experienced tumor reduction

What’s obscured in the above is that this drug results in 0 months increased longevity, that is, it had no effect on the longevity of the patients.

The ORR (overall remission rate:  Medicynical clarification) was significantly higher in the cabozantinib arm (27% versus 0%; p<0.0001) and all were partial responses.  The median response duration was 14.7 months (95% CI: 11.1, 19.3). No statistically significant difference in overall survival was observed between the treatment arms at the planned interim analysis and in an updated survival analysis requested by FDA.

Medicynical Note:  This is a new one for me.  Other new miracle agents often have limited efficacy with say two months median survival improvement.  But this is the first such drug being actively promoted, that I can recall, that has no survival benefit. 

Maybe this is yet another reason we spend more on health care than any other country in the world….by a wide margin. 

Cost Matters: Colon Cancer, Zaltrap (ziv-afibercept)

Sounds crazy, a drug (Zaltrap) costing $11,000/month, with little efficacy is being actively promoted to desperate patients.  A classic case of any promise of efficacy, no matter how small, or how expensive, being irresistible to those with dread diseases. 

What’s even more amazing this article makes the righteous argument that another drug costing only (sic) $5000/month (Avastin)  offering similar (in-)efficacy should be used in it’s stead. 

The “benefit” of these super expensive drugs is roughly the same,  a miniscule 1.4 months median survival.

Medicynical Note:  It’s good that Sloan Kettering finally seems to recognize the folly of a minimally effective agent costing so much.  The benefits, by the way,  are truly minimal.  When a drug offers a median benefit of 1.4 months it means that half the people got less than that benefit (at $11,000/month).  True, half did better but the same could be said of the conventional regimen or placebo with which it’s compared. 

Does 1.4 months median benefit justify the expenditure of over $60,000/year (more than the median or average income of families in our country) on a single drug?  And this expense doesn’t include doctor’s fees, lab costs or imaging expenses. 

Hopeful but Speculative Breast Cancer Gene Analysis

Nature this week published the report of on molecular portraits of breast cancer.  The study has received wide publicity as a major breakthrough, even in our local newspaper which features it as the lead story on page one.  (More a reflection of a low news weekend in a small town than the reality of the study)

As noted on the Genome Web site:  

  “This study has now provided a near complete framework for the genetic causes of breast cancer,” corresponding author Charles Perou, a genetics researcher with the University of North Carolina at Chapel Hill and the Lineberger Comprehensive Cancer Center, said in a statement, “which will significantly impact clinical medicine in the coming years as these genetic markers are evaluated as possible markers of therapeutic responsiveness.”

And:

“The biological finding of the four main breast cancer subtypes caused by different subsets of genetic and epigenetic abnormalities raises the hypothesis that much of the clinically observable plasticity and heterogeneity occurs within, and not across, these major biological subtypes of breast cancer,” Perou and his co-authors noted.

Medicynical Note:  This could be a major breakthrough in understanding the behavior of this group of  cancers.  Grouping these tumors by genetic defect also provides some hints at potentially effective treatments.  

It should be pointed out that all the potential “benefits” are  unproven.  

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.