37 replies to this topic

[scuba]

http://www.washingto...ry.html?hpid=z1

[pamsouth]

Scuba, 

I see the Washington Post front page is on National Security.  Is there a tab to click onto the link to Ponatinib, or did I miss something?

PamSouth

[scuba]

Ooops.....

http://www.onclive.c...in-CML-Subtypes

Sorry about that. I was sending the Washington Post article on cyber security to my son in the Air Force who is a cyber security expert.

[Tedsey]

Thanks Scub!  I am sorry I have not answered your question yet on a different thread.  Anyway when Dr Cortes says, "Two-thirds of patients had failed three tyrosine kinase inhibitors, so this was a very, very heavily treated population."  He means those in the Pontanib trial, right?  I cannot imagine 2/3 of CML patients overall have failed 3 TKIs.  That would be scary.  Thanks for posting this!

Teds

[scuba]

Hi Teds,

Yes, he means the Ponatinib trial. Patients were in the trial only because they had failed the other TKI's (most notably because of the T315i mutation). He told me in separate communication that he is beginning to use Ponatinib as first line therapy (i.e. newly diagnosed patients). I find that interesting.

[Tedsey]

This is very good news for many people with T315i.  Nevertheless, the overall numbers do not not appear to be any better than the other 3 TKIs.   It only brings a good percentage of CP patients to MCyR.  Complete or MMR would be much more promising. The numbers in the article just don't seem to be all that.  A cure would be much better or a drug that would bring a patient from AP or BP to CP or CCyR.  Guess I am dreaming... 

It is interesting that success is sung if you mathematically support extending the life of some people within a short amount of time (ex. 10 or 6 months).  Please forgive me for being sarcastic, but "big whoop".  I would like to live long enough to see my kids grow up, collect social security, and join the AARP.  That will take decades.  All I can say is that I appreciate all the efforts and time put into this.  And, it is not good enough. 

Call me an ingrate, but still, with all these, so called, CML advances I read, it all still boils down to a SCT.  The longer you can put it off the better?  Maybe so.  If buying time, no matter how long is what this game is all about, again, I appreciate the efforts and time put into that, and again, it is not good enough.  I cannot get excited over this article for anyone but those with the T315i mutation or for those who have issues tolerating the other TKIs.

I'd also like to know how some of the subjects died due to the trial.  But, we are cheerfully told that it is not more than in any other trial, so I guess that is all fine and dandy.  Kinda sad how the author glosses over this.  Kinda insensitive.  These were real people who wanted to live.  Death is failure in this respect.  But let's just push that off to the side.  Too bad it didn't work for them or knocked them off. 

Sorry if this post seems a little schizophrenic.  I wrote to soon and needed to let the stats sink in a little.

Teds 

[Happycat]

Teds,

I agree, most patients with cancer are not looking for a few more months. They want years and decades!  Unfortunately, cancer is such a tough nut to crack that oncologists consider a handful of months extra survival to be a "success". For the patients, it's a massive failure.

Cancer is such a awful disease. Look at how it skews perceptions of success. Your treatment is a success because you gained a few months of time. But no one considers all the years that were stolen from you, the weddings, graduations, baptisms, school plays, and little moments of sunshine you missed.

Bitter pill, isn't it? 

We are fortunate to have TKIs for our cancer. So many others do not have that option.  Here's hoping they get some years back, too.

Traci

[chriskuo]

The results are short term because they wanted to gather data to go for FDA approval early next year (for patients which have failed or cannot tolerate other TKI).

I'm sure they will continue to follow these subjects to see what the results are for deeper levels of response.

Al so, they will be starting a new trial for patients who ha be not been treated.

[TeddyB]

Hey Tedsy, hope your feeling well today.

Remember the majority of those numbers from the Ponatinib trials were from people who had already failed at Sprycel or Tasigina, and the majority even all three current tki`s, and people were also in AP and BP, so therefore the Ponatinib numbers were actually pretty good.

It means if you are still in chronic phase there is a 54% (70% if you have t315i) chance that Ponatinib will work for you even if Gleevec, Tasigna and Sprycel fails you, and luckily that doesnt apply to more than a few % for those with CML. Look at it this way: If 90% of CML`rs do well on Gleevec, Sprycel or Tasigna, and another 5% will do well with Ponatinib, and hopefully a few % more with Bosutinib, then that is a pretty good number all in all, >95%. We need to learn more about who will respond better to Ponatinib or Bosutinib after the three other tki`s have failed, so that more lives can be saved, and right now that is in a very early learning process, after the trials they will hopefully know more about which patients to put on which drug for an optimal response.

The follow up has not been that long either, only 10 months, that doesnt mean they just lived 10 months, hopefully in 10 years we will still see the majority of people who started out on Ponatinib after other tki failure still responding well to Ponatinib.

At least thats how i read those numbers in the article, i hope it makes feel somewhat more optimistic about the future

As for the death numbers in the trial, those suck no matter how you look at it I know if i was in BP CML or had ALL, i would think a SCT was the way to go, and not a drug trial, unless there were earlier numbers to support a very good level of response. But for those in their 70`s, 80`s and even 90`s that might not had been an option, and for those patients, the extra added months may have been worth it.

I too am hoping for a cure, and i am optimistic, im hopefull that in 5-10 years something will have "come up", hopefully sooner!!!!!

Other than that, the SCT numbers seem to get better with each year, and new drugs are developed/found for GVHD, so each day we can stay on a tki without the disease progressing that is a small ‰ of a SCT going in our favor if it ever comes to that.

On a completely different note, i read some alarming numbers from Sandy C over at the cmlsupport uk forum, that only 25% of CML patients were adhering 100% to therapy, those are very alarming numbers.

The exact phrase was: "Patient adherence to treatment is poor with fewer than 25% of patients perfectly adhering to their therapy"

Anyways enough rambling from me, have a great weekend!!!

Teddy

[Trey]

The standard method of showing that a drug is worth pursuing is that it does better than existing drugs, at least for some population.  Ponatinib is significant for the T315i treatment alone.  If that were its only use, it would be a significant advance in CML treatment.  But one could extrapolate from the data so far that Ponatinib as a front-line drug could  be better than Gleevec, Tasigna, and Sprycel, and that the effectiveness could be at least equal to the best of them, and maybe better than all of them. 

However, a big issue is side effects profile.  If Ponatinib does not have the pleural effusion of a Sprycel, and is equal or better in effectiveness, then it will be better than Sprycel, and there is some evidence that this will be the case.  But Ponatinib also inhibits some kinases that none of the existing CML TKI drugs inhibit, particularly the FGFR family of kinases*.  That will bring into play some new side effects which a larger population of patients will bring to the forefront, so maybe we will trade side effects, which can sometimes be a good thing.  But overall it is disappointing for CML patients that Ponatinib will inhibit FGFR kinases, since that does not help CML patients, and will undoubtedly have side effects.

http://www.dddmag.co...ts-fgfr-kinases

If Ponatinib is approved in 2013, it will be for those who have failed all existing TKI drugs, and for those with T315i as front-line drug.  Then after a year or so ARIAD would seek approval for Ponatinib as a front line drug. 

* FGFR Kinase:

http://en.wikipedia....t_growth_factor

[Judy2]

Hi Trey,

Would you translate for me what side effects you would have if the FGFR family of kinases were inhibited?

Thanks,

Judy

[Trey]

It is not easy to predict drug side effects.  But when treating CML, inhibiting "off-target" kinases (i.e., inhibiting kinases other than BCR-ABL) inevitably brings side effects.  So far in limited patient populations and with limited time on the drug, the side effects for Ponatinib are similar to existing TKI drugs, but as we have seen, the advertised side effects upon FDA approval are expanded as the patient population grows, and as time on the drug becomes longer. 

The main advertised side effects for Ponatinib are pancreatitis, low platelets, dry skin and/or rash, abdominal pain, headaches.  Lesser ones are fatigue and joint pain. 

Again, Ponatinib will be a welcome addition to the CML treatment arsenal.  I was just surprised to find it inhibiting an entirely new class of kinases not seen in the current TKI drugs.  When will we ever see a pure ABL or BCR-ABL inhibitor? 

[Judy2]

Thanks Trey. I was wondering if the inhibition of the FGFR family of  kinases meant there were entirely new side effects not seen on the other drugs. I was trying to decipher the article you linked and thought it was talking about something vascular. I, too, wish these targeted drugs didn't inhibit anything other than what they needed to inhibit to treat our CML.

Judy

[wallystl]

Happy Monday.  "Big Whoop"????  I'm living on Ponatinib after failing on 3 TKI's and developing t315i mutation.  You Tedsey should perhaps think before you post with such sarcasm.  Big Whoop, Really?

[pammartin]

Ponatinib does work for some, just as the other three work for individuals.  For a long time Sprycel was the latest and greatest, but I found it interesting while at Cleveland Clinic they were not really as excited about Ponatinib as I thought they would be.  I am happy for you Wally it is working, but I also have to jump in to defend Tedsey because as was stated, the only cure remains a transplant and there is not one person I have met, or read posts on this board who would choose that option over trying to make it as long as we can on the meds without failing.

Although treatment is productive, it is frightening, we do not know if it will continue to work or how well it will work, it is the luck of the draw.  If there is annoyance and sarcasm it is not at your excellent response to the Ponatinib, instead it is at this damned disease.

Pam

[Trey]

It would be helpful if some of those on the Ponatinib trial discussed side effects they have experienced. 

[CallMeLucky]

Teds,

I hear your frustration, but I wanted to respond to the point about it all boiling down to an SCT.  I don't think that is the reality of the situation.  Most people who were in the Gleevec trial are still alive on Gleevec, that is the reality.  Some have it harder than others, some sadly it has not worked for, but overall the treatment works and there are many people alive well beyond the years they would have been.  We have one of the best survival rates of all cancers based on our TKI treatment and while it may not be the easiest life, for most it is a functional life that is not filled with misery. 

[pamsouth]

Wallysti,

I am glad it is working for you.  But until a drug is out for several years and there have been a vast number of patients on the drug, then it really is to early to tell, the full impact of the drug, short, med, long.  It takes years and many patients to tell the whole story.

PamSouth

[Tedsey]

Wally,

This is what I wrote.  "This is very good news for many people with T315," and for people who cannot tolerate the other TKIs, (or in your case, for those who the approved TKIs don't work).   I think you misunderstood what I said.  In no way am I knocking Ponatinib.  And I am thrilled that you are doing so well on it and I am glad it is on its way to getting approved.  I hope you continue to live a long and healthy life on Ponatinib or a new and better drug that may come along in the future.  I just get skeptical that researchers are actively looking for a cure for CML.  Since the disease seems to respond so well to drug therapy, and there can be much money made by developing more, it just makes me wonder if maybe a cure is not the top priority of the most funded and productive in the industry.  But I don't know.

Am I thankful for the drugs?  You betchya!  I am not exactly sure how long the Ponatinib trial has been going on.  I think it takes years for FDA approval though.  The report for 6 and 10 months seems promising if patients can get a much better response in the future.  I sure hope so with all my heart.  I guess I wanted to see miracle stats, especially for those with more advanced CML.  Well, who knows?  Maybe they are and will become miracle stats.

I guess I get frustrated and sad that no matter how good the drugs can be, they don't work for every one of us.  It would be so nice if that were the case (in all stages of CML so no one has to go through a SCT until doctors can make them extremely survivable and with  no or few issues after recovery for adults--but I don't think this will happen).  And I get sad and frustrated that a cure seems to be light years away.

The "big whoop" I mentioned is when doctors/researchers feel they deserve big kudos for keeping someone alive for a short time longer with some cancers (if you really can quantify that accurately).  Six, ten months, I guess a year, or even 20 would seem like I got shortchanged (of course, not because of the doctors, but because of the disease that cannot always be controlled).  I have two little kids and I so want to see them grow up.  So far, I am holding CCyR, but not MMR (according to my onc) on Sprycel.  Wish I could get a better result, but stable means no progression.  If I can stay this way and get old enough to join AARP and retire with my husband (God willing we all survive), I will be happy, especially if the TKIs don't appear to have any adverse, long-lasting side-effects, like destroying our livers or something like that.  I guess I would like to see more humility.  Of course if I were given the choice to die now or live six more months, that is a no-brainer.  I love my life and my family.  But I want to live as long as most of these doctors and researchers.

I guess I just want to have a care-free life like the other mothers of young children I talk to at toddler classes, (i.e. ballet, t-ball, preschool).  Although in most ways I can fake it, I get sad and jealous (but I never wish what I am going through on anyone).  And every time I go anywhere with my kids, to the grocery store, museums, dentist, theme parks, shoe shopping, classes, whatever,  I NEVER forget that I am lucky I have the strength to do this and the disease has been is seemingly in check for almost 3 years.  There is not a day that goes by that I am not grateful, or when a major life event happens, that I send a "thank you" out into the universe (and mostly to Dr Druker who got this all started).  That I do this is not an exaggeration or a joke.  I know no one can be guaranteed a long life.  However, the average female makes it to somewhere around 78 years in the USA.  Ironically, it is 80 or 82 for both sexes on Manhattan.  I think you have a teenage son (forgive me if I mixed you up with someone else).  I hope that you will see him grow up, marry or fall in love, and see your grandchildren if your kids want kids (if they don't I just wish you a happy old age and retirement).  I want the same for all of us.

And as Traci says, I also wish our other sisters and brothers in this nasty cancer experience a, more or less, easy to swallow pill that works with great success.  There is no denying that these drugs work for most people with CML.  Moreover, the drugs will probably help patients exceed the pretty solid 95% (or is it almost 98% now) five-year survival rate that is so often quoted.

All the best and long life to you, Wally.  I know you too have been through a lot.

Tedsey

[Sneezy12]

You are being unfare to Physicians when you accuse them of giving themselves "kudos" for their successful research resulting in keeping patients alive for a short time. While it may not represent a cure, it does represent a small but significant step TOWARDS a cure.

You are also incorrect in implying that Researchers are not really aggressively looking for a cure, since more money can be made for companies by selling the TKI's. No legitimate scientist operates this way, including those that are employed by Pharmaceutical Companies. Frank