In Cancer 'Cheaper' Is Not Better, Just Less Available

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  • 06/04/2012

Too often media coverage of scientific studies are rife with what behavioral economist Daniel Kahenman calls "the availability heuristic."   The availability heuristic is a mental shortcut that uses the ease with which examples come to mind to make judgements about the probability of events. 

In reporting terms that translates into taking top line results and fitting into a pre-conception or narrative.

Such is the case with reporting on a study comparing the effectiveness of paclitaxel and bevacizumab with a nano-sized form of paclitaxel called Abraxane & Avastin as well as Xyempra and Avastin.

Here's the MedPage account of the study

"Patients with metastatic breast cancer did just as well -- and maybe better -- with paclitaxel-based chemotherapy compared with two newer, more expensive agents, results of a randomized trial showed.

First-line treatment with weekly paclitaxel and bevacizumab (Avastin) resulted in a median progression-free survival (PFS) of 10.6 months compared with 9.2 months with nanoparticle albumin-bound paclitaxel (nab-paclitaxel or Abraxane) and 7.6 months with ixabepilone (Ixempra), each paired with bevacizumab.

The ixabepilone arm had significantly worse PFS at an interim analysis and was dropped from the trial.

Patients who received paclitaxel also had less peripheral neuropathy than with either of the other drugs, and less hematologic toxicity than those who received nab-paclitaxel, Hope Rugo, MD, reported here at the American Society of Clinical Oncology meeting.

"Neither weekly nab-paclitaxel nor ixabepilone is superior to weekly paclitaxel," Rugo, of the University of California San Francisco, said during an ASCO press briefing. "Weekly paclitaxel appears to offer better progression-free survival than ixabepilone."

"These data suggest that similar patients could be appropriately treated with weekly paclitaxel," she added.

During the discussion that followed her presentation, Rugo described cost issues surrounding cancer therapies as "enormously complicated," but said that generic drugs such as paclitaxel will always be less expensive than newer drugs that are not available as generics.

Funded by the National Cancer Institute (NCI), the trial came about as a result of recent developments in the treatment of metastatic breast cancer."

Of course, the funding had nothing to do with comparative effectiveness research efforts to claim that cheaper is better.   But I digress

The study and the Medpage article is yet more evidence --  pouring in at the ASCO meeting as I write -- that targeted therapies or targeted use of therapies based on biomarkers and mechanisms of action implicated in both toxicity and tumor response -- is replacing the one size fits all approaches and comparisions that NCI supports. 

The fact that you have to get into the weeds about the study and have to put it into context of other studies looking at Abraxane and Xyempra underscores this point.

For instance:  Abraxane was designed to be longer lasting and administered at lower doses and less often.  

The study used 150 mg/m2 weekly and has a 30% higher weekly dose intensity than the approved dose of 260 mg/m2 every 3 weeks.  

Still Abraxane has been used in weekly fashion, to great effect: "in phase 2, median progression-free survival (PFS) was 18.9 months for 150 mg/m2 weekly nab-paclitaxel vs 8.5-13.8 months for all other regimens. In phase 3, median PFS for q3w nab-paclitaxel and solvent-based paclitaxel were 5.6 months and 3.5 months, respectively. Weekly nab-paclitaxel resulted in less serious adverse events compared with all other regimens.  
Breast. 2011 Oct;20(5):468-74.

The outlier in all Abraxane studies is the current one.  Why?  Abraxane is formulated as a monotherapy for metastatic breast cancer, not in combination with Avastin.  It's not just a stronger or smaller form of paclixtel.. it also targets a previously unrecognized tumor upregulated path through the blood vessel wall.

Nearly half of the people enrolled in the study dropped out due to toxicity issues.  So in effect, the investigators forced cancer patients to stay on a regimen that was toxic.. 

Yet, even using Abraxane in an off-label manner, patients who took the combo lived an average (again, a suspect number in cancer trials these days) of 9.6 more months compared to 10.4 months for paclixtel and Avastin.

Did the higher toxicity result from the combination of a higher than prescribed dose and using it with Avastin?  They researchers and the media account don't even ask that question.  Instead they hew to the availability heuristic:

 Rugo described cost issues surrounding cancer therapies as "enormously complicated," but said that generic drugs such as paclitaxel will always be less expensive than newer drugs that are not available as generics.

Well, yes they are.  For instance:

1.   One smaller dose of Abraxane costs slightly more than the same as four weeks of paclitaxel.  
2.   Several studies have shown that Abraxane use in women with MBC cuts down on the amount of time and services required to treat toxicity, to administer the drug and enhances quality of life.   For isntance: " Nab-paclitaxel had the lowest incidence of grade III/IV toxicity. This translated to lower overall costs for managing the grade III/IV events relative to both docetaxel and paclitaxel ($597 vs. $2626 vs. $1227). Using the median number of cycles administered and the cost impact of grade III/ IV toxicity, the overall cost for nab-paclitaxel would be $15,105 compared to $15,268 for docetaxel and $3557 for paclitaxel. When treatment preferences were assessed, 20 of 24 (83.3%) respondents selected nab-paclitaxel as their preferred choice compared to only 4 who selected docetaxel."    J Oncol Pharm Pract. 2009 Jun;15(2):67-78.
3.  Then there's the fact that there are severe shortages of  paclitaxel:

Chemo Drug Taxol Shortage Puts Cancer Patients at Risk

So is it worth switching breast cancer patients to a drug that incurs more costs and reduces quality of life, a drug that people die waiting for?  

No one asked or answered that question.  



Center for Medicine in the Public Interest is a nonprofit, non-partisan organization promoting innovative solutions that advance medical progress, reduce health disparities, extend life and make health care more affordable, preventive and patient-centered. CMPI also provides the public, policymakers and the media a reliable source of independent scientific analysis on issues ranging from personalized medicine, food and drug safety, health care reform and comparative effectiveness.

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