FDA Advisory Committee votes against bevacizumab use in metastatic breast cancer

I was not a great fan of bevacizumab for breast cancer  treatment … now FDA agrees that it’s useless!



New report from OCDE (FDA’s Oncology Drug Advisory Meeting) considered the use of bevacizumab in first line therapy combined with chemotherapy “not clinically relevant”.
 
That’s all! Unfortunately for our patients, we all expect good and valuable new treatments; but new drugs must be extensively researched for the benefit of our patients, not drug companies.  


What provokes me is that these studies (E2100, AVADO and RIBBON1) were extensively explored by the drug manufacturer worldwide, as well as it's colon cancer twin study (E3200). For me, these practices sounds creepy … a good study stands by itself.


So on…


In july 22^nd the FDA advisory committee voted 12 / 1 against bevacizumab use in first line metastatic breast cancer, a knockdown against poor science and poor medicine. See how at the OCDE Report pages 25 and 26 (and 8 below):

“IV. SUMMARY      
The addition of bevacizumab to docetaxel (AVADO study) and to taxane/anthracyclinebased chemotherapy or to capecitabine (RIBBON1 study) met the pre-specific primary endpoint, with a statistically significant improvement in PFS, however the magnitude of the PFS improvement is not clinically meaningful. The combination of bevacizumab to chemotherapy resulted in an overall increased in serious adverse events, grade 3-5 adverse events, and adverse events related to bevacizumab in both studies. Overall survival data showed hazard ratios favoring the placebo arms for AVADO study and RIBBON1 (taxane/anthracycline cohort), indicating an inferior outcome with the addition of bevacizumab to these chemotherapies.
AVADO and RIBBON 1 are well-conducted, double-blinded trials, with less missing data compared to E2100. The improvement in PFS observed in these two studies, as measured by the hazard ratio and as more commonly expressed by clinicians as the difference in median PFS between the treatment arms, failed to confirm the magnitude of PFS improvement observed in the E2100 trial, the basis for the accelerated approval. The magnitude of treatment effect is clinically important because it is really a measure of delaying symptoms from tumor progression, which has to be weighed against drug toxicity that is present for the duration of treatment
The risk-benefit ratio of bevacizumab when added to the standard the chemotherapeutic regimens serving as standard of care in the AVADO and RIBBON1 studies may not be considered favorable. FDA seeks the Committee’s advice on whether clinical benefit has been demonstrated in these applications.”

Going even deeper on report, we will find some really bad science reported, pasted from page 8:


“The review team did not have confidence in the PFS results because baseline or PFS-determining radiographic scans were missing in 10% of the patients and 34% of the patients were not followed until an IRRC-determined PFS event or the end of the study. In addition, there was a high rate of discordance (50%) between investigator and independent review determined PFS events”.

Ops,

34% of the patients were not followed until an
IRRC-determined PFS event or the end of the study?

50% discordance between investigator and
independent review determined PFS events?

If it is not bad science, I don’t know what it is…

…

Slides presented in PDF format: http://ht.ly/2fntf

Report in PDF format: http://ht.ly/2fQ7X

Are you psychologically inert?

Psychological inertia is what inhibits your creativity and innovative thinking ability.
Recent article at Quality Progress Magazine reminded me about it. Great article written by Aditya Bhalla raised great points about innovation, but psychological inertia types attracted me and were listed as below:
TYPES OF PSYCHOLOGICAL INERTIA

1. Inertia associated with the usual functioning of an object (a computer mouse can be used only for moving the cursor on the screen).
2. Terminological inertia or the use of technical jargon (reduction of the “synthetic inventory” in corporate banks).
3. Inertia caused by usual forms or appearance (scientists must wear coats).
4. Inertia caused by usual properties, conditions or parameters (teams must always have a manager).
5. Inertia caused by usual principles of action or area of knowledge (the application of new lean concepts to manage a team or software professionals).
6. Inertia caused by usual composition or components (a data-entry operation must have a person keying in values into the system).
7. Inertia caused by usual constancy of an object or character (calls to a technical support desk must always progress from lower-skilled staff to higher-skilled staff).
8. Inertia caused by usual dimension (in a call center, there can’t be more than one customer-service representative talking to one customer).
9. Inertia caused by a nonexistent prohibition (you shouldn’t make a sales pitch to an irate customer).
10. Inertia caused by habitual action (underwriting work for any particular customer case cannot be split among several underwriters).
11. Inertia caused by a single solution (the tendency to stop exploring other solution ideas).
12. Inertia caused by mono-object (silo-based thinking to process improvement).
13. Inertia caused by usual value, or importance, of the object (software must be tested by an independent team of testers before release).
14. Inertia caused by traditional conditions of an application.
15. Inertia caused by the known pseudo-similar solution, or the tendency to superficially apply the similar solution that worked in the past (reward structure).
16. Inertia caused by superfluous information (the tendency to provide or seek information not related to the core problem).

As listed by: Aditya Bhalla, in Quality Progress Magazine, June 2010.

Other sources: http://www.triz-journal.com/archives/1998/08/c/index.htm

Are you psychologically inert?

Psychological inertia is what inhibits your creativity and innovative thinking ability.
Recent article at Quality Progress Magazine reminded me about it. Great article written by Aditya Bhalla raised great points about innovation, but psychological inertia types attracted me and were listed as below:

TYPES OF PSYCHOLOGICAL INERTIA

1. Inertia associated with the usual functioning of an object (a computer moouse can be used only for moving the cursor on the screen).
2. Terminological inertia or the use of technical jargon (reduction of the “synthetic inventory” in corporate banks).
3. Inertia caused by usual forms or appearance (scientists must wear coats).
4. Inertia caused by usual properties, conditions or parameters (teams must always have a manager).
5. Inertia caused by usual principles of action or area of knowledge (the application of new lean concepts to manage a team or software professionals).
6. Inertia caused by usual composition or components (a data-entry operation must have a person keying in values into the system).
7. Inertia caused by usual constancy of an object or character (calls to a technical support desk must always progress from lower-skilled staff to higher-skilled staff).
8. Inertia caused by usual dimension (in a call center, there can’t be more than one customer-service representative talking to one customer).
9. Inertia caused by a nonexistent prohibition (you shouldn’t make a sales pitch to an irate customer).
10. Inertia caused by habitual action (underwriting work for any particular customer case cannot be split among several underwriters).
11. Inertia caused by a single solution (the tendency to stop exploring other solution ideas).
12. Inertia caused by mono-object (silo-based thinking to process improvement).
13. Inertia caused by usual value, or importance, of the object (software must be tested by an independent team of testers before release).
14. Inertia caused by traditional conditions of an application.
15. Inertia caused by the known pseudo-similar solution, or the tendency to superficially apply the similar solution that worked in the past (reward structure).
16. Inertia caused by superfluous information (the tendency to provide or seek information not related to the core problem).

As listed by: Aditya Bhalla, in Quality Progress Magazine, June 2010.

Other sources: http://www.triz-journal.com/archives/1998/08/c/index.htm

http://www.facebook.com/group.php?gid=43461176682

Treating heartburns with NSAIDs prevents gastric cancer?

Recent report at JCO shows that, in patients with H pylori positive peptic ulcers, the use of NSAIDs (Nonsteroidal anti-inflammatory drugs) reduces gastric cancer risk. Yes, a protective role against gastric cancer was found in patients using NSAID with H pylori positive gastritis – conflicting?
Maybe. ]
We know that NSAIDs plays protective role in gastric (and colon) cancer carcinogenesis, but using it as a preventive measure in gastric ulcer – that’s new… we usually defer using these drugs in patients with peptic diseases. Well, data available is telling that it is protective!!!
Evidence is still growing that inflammation plays major role in cancer development (affecting carcinogenesis processes).
More than 52 thousand patients were studied in cohorts for regular and never NSAIDs users. Never users had higher risk for gastric cancer, if they were H pylori positive: “On multivariate analysis, regular NSAID use was an independent protective factor for gastric cancer development, especially in H pylori-associated patients.”
So what to do? Take NSAID when heartburning?
Not so…. Ask your doctor about it! Ask about H pylori treatment and gastric cancer risks.

The link for the article is: http://ht.ly/2crZd

Article detais:
Chun-Ying Wu, Ming-Shiang Wu, Ken N. Kuo, Chang-Bi Wang, Yi-Ju Chen, Jaw-Town Lin
Effective Reduction of Gastric Cancer Risk With Regular Use of Nonsteroidal Anti-Inflammatory Drugs in Helicobacter Pylori–Infected Patients
Journal of Clinical Oncology, Vol 28, No 18 (June 20), 2010: pp. 2952-2957

Everolimus or sirolimus in breast cancer, why not?

Some interesting studies are being presented at 2010’s ASCO, in Chicago about the effectiveness of everolimus in HER-2 positive breast cancer (a mutation that affects about 25% of all breast cancers patients).
The point is about one single issue: everolimus and sirolimus are virtually the same drug, major difference is about blood clearance and half life.
Why not test sirolimus in breast cancer? It is cheaper (longer half life, less drug needed, older drug, large experience, use learning curve completed), it is safe … but surely not interesting for business …
See at:
Sirolimus vs everolimus: http://ht.ly/1Uths
One ASCO paper regarding everolimus: http://ht.ly/1UtjP

Statin Use and Cancer Risk Reduction News

I’m not a statins’ fan, I have a personal negative impression about these drugs, not specially related to anything but their name - “something-statin …” sounds bad (but sounds that it can “stat” certain cancers development). Beside my personal opinion, more and more evidence is available about the “generic” benefit of its use, at least in cancer risk reduction.
Long-term treatment with statins helps reduce cholesterol levels, heart attack and stroke incidence. There is good evidence about these benefits and these drugs are approved for this use (see links below).

The discussion now is about incidental benefits… two recent reports, from BMJ and JCO discusses the unintended effect of statins in England and Wales and the better outcome of men with prostate cancer using this class of drugs at Chicago University.

The facts:

The England and Wales study was a huge cohort study, with 2 million patients included, read it:
“Individual statins were not significantly associated with risk of Parkinson’s disease, rheumatoid arthritis, venous thromboembolism, dementia, osteoporotic fracture, gastric cancer, colon cancer, lung cancer, melanoma, renal cancer, breast cancer, or prostate cancer. Statin use was associated with decreased risks of oesophageal cancer but increased risks of moderate or serious liver dysfunction, acute renal failure, moderate or serious myopathy, and cataract. Adverse effects were similar across statin types for each outcome except liver dysfunction where risks were highest for fluvastatin. A dose-response effect was apparent for acute renal failure and liver dysfunction. All increased risks persisted during treatment and were highest in the first year.”

The study can be considered negative except for the esophageal cancer reduction, with considerable risk of toxic effects (liver, muscles, kidney, eyes). The study has a broad and generic view, and authors consider that future studies with individualized risk analysis are needed.

The University of Chicago Study identified better outcome for patients using statins and treated for prostate cancer. It is a retrospective study with 691 men, 189 used statins and all were treated between 1988 and 2006. Patients under statins stood longer without biochemical recurrence, longer for salvage treatment and longer relapse-free survival. In their analysis, lower levels of cholesterol (mainly LDL) were associated with better outcome from low to high risk patients.

We had preclinical evidence of potential anticancer activity of statins with antiproliferative, proapoptotic, and radiosensitizing properties.
Now we have some reasonable clinical evidence.

So what?

Should I get some statin pills to prevent prostate or esophageal cancer?
Or should I exercise to reduce my LDL level (where probably the benefit stands)?

Keep moving….

Link to evidence of benefit about statins use: http://ht.ly/1R7cM
England and Wales study: http://ht.ly/1R7iT
Chicago Study: http://ht.ly/1R7eS

Fixing Medicare’s Physician Payment System, going to the non-lean solution: cutting wages….

Most of us in Brazil know where this kind of solution is going to end: poorer services, higher costs, neglected quality…. Cut workers income is the best solution to worsen performance… any lean beginner is aware about the impact of cutting costs by cutting wages and personnel, it is formally recommended not to do such things…healthcare reform starts on that.
Back in Brazil quite similar reform took place few decades ago… the impact on healthcare quality is measurable: Brazil doesn’t have 500 (yes, it’s less than five hundred) nationally certified healthcare units/centers (hospitals, labs, clinics, etc.). Brazil has 200 million inhabitants and more than 200,000 healthcare units/centers. Sao Paulo State concentrates 2/3 of these quality certificates, and has more than 50,000 healthcare units/centers. Nobody worried about quality assurance…
Cut costs by cutting service reimbursement are another form of what people now call “brazilification” (I heard it for the first time back in 2000, now it’s getting popular…).
See NEJM publication: http://ht.ly/1IoJa