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Old 09-09-2020, 08:22 AM   #1
Nguyen
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Rapid Breast Cancer Disease Progression Following Cyclin Dependent Kinase 4 and 6 Inh

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5559961/

Although an extremely small sample size (4), it is scary to read for us at the moment. I haven't been able to find (yet) more study one way or the other about this.

Nguyen
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Old 09-09-2020, 04:06 PM   #2
donocco
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Re: Rapid Breast Cancer Disease Progression Following Cyclin Dependent Kinase 4 and 6

Nguyen

Thank you for these 2 articles. I printed them both of them. The CDK4/CDK6 inhibitors
can have hematological side effects that require discontinuation. I wonder how common rapid progression is? Any percent is scary. The advertising for them on TV is non stop.

Paul
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Old 09-14-2020, 12:09 PM   #3
donocco
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Re: Rapid Breast Cancer Disease Progression Following Cyclin Dependent Kinase 4 and 6

I read the two articles that Nguyen posted. I saw something very interesting in the second one. When they compared the time to progression when using the anti-estrogen drug alone, it was 10 months. With the combo of Palbociclib plus the estrogen inhibitor it 20 months time to progression.This seems pretty dramatic evidence pointing to the fact that CyclinD 4/6 inhibitors are extremely effective drugs.

Things are not that dramatic when you look at the important thing OVERALL SURVIVAL. With the Estrogen inhibitor it was 33 months. With the ibrance/ER inhibitor combo it was 37 months. If the increase in Time to progression correlated well with overall survival yuld expect 60 months overall survival. The fact is, time to progression increase correlates little with overall survival. When multiple drugs are used together, you often get increases in TTP with the combo but actual decreases in the overall survival, probably due to the increased toxicity of the combination therapy. It seems the FDA is using increases in the time to progression to approve new anticancer drugs. Maybe I misread something. Ill reread the pharmacy journal article and do some more research.

Of the 3 commonly used CDK-4,6 inhibitors, Abemicliclib or versenio seems to have less severe neutropenia.

Paul
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Old 09-15-2020, 12:50 PM   #4
Nguyen
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Re: Rapid Breast Cancer Disease Progression Following Cyclin Dependent Kinase 4 and 6

Abemaciclib with continuous dosing v.s 3 weeks on 1 off for the others CDK4/6, abemaciclib does have less severe neutropenia. Unfortunately, we still have to temporary hold treatment due to low count. But my wife is atypical in that ever since stem-cell treatment some 20 odd years ago, her immune system recovers to only half of normal. We don't even know yet if it work for her.

Anyway, I need to re-emphasize that 4 is the total sample size that this article was based on. It's cited by only 7 other articles and its impact factor is only 3.5.

Nguyen
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Old 09-17-2020, 12:47 PM   #5
donocco
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Re: Rapid Breast Cancer Disease Progression Following Cyclin Dependent Kinase 4 and 6

Nguygen

I am sorry your wife is having this problem. In the medical science world it is publish or perish. Its like the news. The more spectacular the headline the more attention the article gets. To use an analogy, here in California we get earthquakes. Sometimes they are serious. It is almost amusing to watch the local news scrambling to find someone that died during the earthquake so the headline can read " KILLER earthquake hits Southern California. Sometimes they get desperate and find someone who died in an area far from the epicenter. You wonder if the fatality is a 96 year old man who died in in his sleep but during the earthquake.

My main concern is the FDA. They want to keep their jobs. naturally, particularly with all of the power they have. In order to keep your job, you have to please your boss. This is unarguable. Congress made the laws that gave the FDA dictatorial powers. Congress is the boss of the FDA. The congressmen want lobby money for reelection. The drug companies are major lobbiests in the Health Care System. The more money they make the more Lobby money Congress gets. Its to the FDA's advantage from a job security point of view to approve as many drugs as possible.

In the days before insurance, people paid for their own meds. The price had to be affordable. Oral Zofran at 4 dollars a pill was the most expensive drug in 1987. Now the sky is the limit. The insurance companies probably encourage these high drug prices. It keeps people totally dependent on insurance coverage. In other words paying expensive premiums.

To use Time to progression increases as a reason to an oncologydrug is inexcusable. Time to
progression increases have little to do with increases in overall survival. Before the insurance takeover of medicine the drug companies had to produce useful drugs to make money. if we were back in 1987, the docs (who had private practices) would prescribe the breast cancer drug that kept the patients alive the longest. The drug company that produced the drug with the longest overall survival made the most money. It is a different story now. They can put any thing on the market and charge thousands per capsule. The IV PD-1 inhibitors cost 30,000 dollars a dose an d about 200 dollars to produce. This has to change if we are going to see real advances in cancer therapy. But how? A big question


Paul



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