38 replies to this topic

[td1961]

Dear Fellow CMLers,

I have just read and signed the online petition:

   "Petition to the FDA calling for clarification on the standing of the  drug Omacetaxine Mepesuccinate, and the issue of non-standardized  in-vitro diagnostics."

hosted on the web by PetitionOnline.com, the free online petition
service, at:

   http://www.PetitionO...e.com/FDAOMACE/

I personally agree with what this petition says, and I think you might
agree, too.  If you can spare a moment, please take a look, and consider
signing yourself. I personally don't have any mutations that I know of but who knows when

this new drug might also be my saving grace? It will definitely help those who have the T315I mutation right now!

Best wishes and be healthy,

Tracy

[BethG]

Tracy,

I read the petition and wondered if there was background anywhere to find out more about the issue/politics behind this. Who is is actually behind the petition? Was it a patient or is the company developing the drug sponsoring this petition behind the scenes?

From what I understand (and please realize it has been a year since I have looked at this), this drug isn't a super duper "home run", but it does show some activity. (Please correct me if I'm wrong here. Perhaps Trey knows?) I have the T315i mutation and the doctors I have dealt with have not been super excited about this compound as a treatment option, like they are about others in the pipeline.

Just curious and thank you for posting this!

Beth

[td1961]

Beth,

Politics aside, I learned of this from Jerry's site over at Newcmldrug.com. It's something that Cheryl Anne and Greg are doing. Here's the URL: http://www.newcmldru...016&Reply=15016 I thought it would be helpful no matter who's doing it since we never know what drug is going to work for us and when we might be next to need it.

Tracy

[Trey]

This came from a CML patient who feels that the FDA is not giving adequate consideration to a drug called Omacetaxine Mepesuccinate, which is actually a very old drug derived from the cyprus tree, and re-named.  It was formerly known as Homoharringtonine and used by the Chinese for thousands of years. The basis of the patient's complaint is that the patient feels that the FDA is changing the rules of the game.  I have no firm opinion on that.  But the clinical trial CCR rate for the drug is only 10% among those with advanced disease.  That should tell the story.

http://docs.google.com/viewer?a=v&q=cache:D2yd_INKkOcJ:www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/OncologicDrugsAdvisoryCommittee/UCM204341.pdf+Omacetaxine+Mepesuccinate+fda+review&hl=en&gl=us&pid=bl&srcid=ADGEESi1A1uyY-jCG38LY4vwtcQza3DDwjweadhuv0vjIBuFXryOjev4PYKxd-98q5eZZSwdaAbP16ILUldaltcOV4GDIt-6lLEbs0dQ1XBQRjb4OQS9Wcqb-7A4yC75TOp8CmlpsbiN&sig=AHIEtbTpZuVc0tGeBoTqgrmH0iK58FvOsQ

http://www.cancer.gov/search/ViewClinicalTrials.aspx?cdrid=514196&version=HealthProfessional&protocolsearchid=7745879

http://cancerres.aacrjournals.org/cgi/reprint/46/2/967.pdf

Personally, although I understand and appreciate Tracey's intent, I would rather see the drug go through the stages of the clinical trial process and prove itself useful or not.  The FDA gave the drug a priority review, so they are not being "refusniks" about this drug, as I see it.  But that is just a personal opinion.

[cherylannes]

Hi Trey,

Actually to be fair, I was at the FDA ODAC meeting and everyone who voted on the issue said that if the question were about clinical efficacy of the drug, there was no question, they all felt that it should be approved.  The clinical efficacy of the drug is higher than you are stating, it is actually around 20%, but that was only for the 66 patients included in the data that were accrued up to the time ChemGenex submitted it for the FDA review process.  There is data now on over 200 patients that have been treated with this drug.  This data was accrued after the FDA filing and so it is not part of the filing.  This is data from patients for whom nothing else existed and they faced a very grave future.

Putting these issues aside,  the best question to ask yourself is what would you do if, heaven forbid, you were suddenly found to have the T315I mutation?  What is your current option?  There are now three options: 1.) compassionate use of Omacetaxine, 2.) clinical trial with the Ariad drug, or 3.) bone marrow transplant.  Let's be clear on several issues, we are not a one size fits all disease or patient population for that matter.   While there are some patients who are responding to the Ariad drug for example, I know that there are other patients who are not responding to it.  Then of course what happens if you do not have a bone marrow match?  What happens if you are 60 years old or older and not a good candidate for a bone marrow transplant? 

Please go to the CML Society of Canada's website (www.cmlsociety.org)  or the National CML Society's website (www.nationalcmlsociety.org) and read the personal story of Susanne Carrow who also spoke at the FDA ODAC meeting.  How many of us can relate to going through what she has gone through?

The simple fact is that we need answers and the last I checked we still do not have a cure for this disease.  From my perspective, while there are still patients struggling with this disease we owe it to them to raise our voices in support of the struggle.

We are not working with ChemGenex in any way on this issue - this is not about brand or company loyalty.

This is a group of concerned patients showing compassion for our fellow CML journeyers who may be less fortunate than ourselves.  We thank the support and guidance of Dr. Michael Mauro, Dr. H. Kantarjian and others who helped us with the wording of this petition.

We urge everyone who is either affected directly by CML, their family members, friends and their physicians to sign the petition.

http://www.petitiono...E/petition.html

May we all be well and healthy!

Cheryl-Anne

[PhilB]

I'm not a huge fan of this particular drug either as although it's certainly better than nothing if transplant is not an option for you, there are much more promising drugs in the pipeline.  I do think it is very important though that we do support this petition as if we don't get this mutation testing issue sorted out then none of those upcoming drugs will get approval either and that really will be criminal.

Phil

[Trey]

Cheryl Anne,

Good to hear from you on this issue.  One question I have is that you said: "The clinical efficacy of the drug is higher than you are stating, it is  actually around 20%..."

My statistics on drug efficacy as 10% for Complete Cytogenetic Response (CCR/CCyR) still seem to be correct, as far as I can tell, and came from the FDA report dated Feb 2010, which says (quoting):

• The response rate observed in the efficacy study was low. For the chronic
phase cohort of 40 patients, the MCyR rate was 15% (10% CCyR + 5%
PCyR) with a median duration of response of 7.7 months. For the
accelerated phase cohort of 16 patients, the MCyR rate was 6.3% and
CHR rate was 31.3% with a median of duration of response of 22 weeks.
There were no responders in the BP cohort.

(From page 6 of the FDA report:)

http://docs.google.com/viewer?a=v&q=cache:D2yd_INKkOcJ:www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/Drugs/OncologicDrugsAdvisoryCommittee/UCM204341.pdf+Omacetaxine+Mepesuccinate+fda+review&hl=en&gl=us&pid=bl&srcid=ADGEESi1A1uyY-jCG38LY4vwtcQza3DDwjweadhuv0vjIBuFXryOjev4PYKxd-98q5eZZSwdaAbP16ILUldaltcOV4GDIt-6lLEbs0dQ1XBQRjb4OQS9Wcqb-7A4yC75TOp8CmlpsbiN&sig=AHIEtbTpZuVc0tGeBoTqgrmH0iK58FvOsQ

So the FDA says that there was a 10% Complete Cytogenetic Response rate, and various types of other lesser responses.  And these responses were only for Chronic Phase patients, and no CCRs for any Accelerated Phase patients, and Blast Phase patients had no response at all.  The report also states that 35% of patients did NOT have a confirmed T315i mutation.  If I am mis-reading the FDA report I would be grateful if you could provide clarification.

Again, I have no firm opinion about whether the FDA treated this company fairly.  I am only looking at response rates.  There are other developmental drugs that appear to have far better efficacy against the T315i.  If patients use this drug when they could have used a better drug, that would not be in their best interests.

[cherylannes]

Hi Trey,

Sorry for the delay in replying to your post, I have been traveling all day.

Let me see if I understand you correctly; are you saying (1)that since seemingly only 10% of the patients in CP in the study achieved a CCR, and (2)since 35% of the patients did not have a confirmation of the T315I mutation, then this drug, in your opinion should not be approved for market by the FDA.  You further state that (3)there are other drugs in development which you say " appear to have far better efficacy against the T315i" so patients should not be treated with Omacetaxine as it would harm them.

If you do not mind, I will answer this in bullet point form.

(1) Quoted from the FDA transcript of the meeting (Adam Craig): " After median follow-up of 16.3 months, chronic phase patients achieved a 25 percent major cytogenetic response rate.  In keeping with the Nilotinib approval in 2007, unconfirmed and confirmed major cytogenetic responses were included in the analysis, as both are accepted surrogate markers of survival in CML.  The FDA reports a 15 percent response rate, as they only included confirmed responses in their analysis. - note this next part was added by me on May 27 it is a direct quote from the transcript  "In summary of the efficacy data, the Pilot Study 202 data shows that omacetaxine therapy provides clinically meaningful benefit to patients who have no

effective treatment options.  Chronic phase patients achieved durable hematologic and cytogenetic responses with rapid onset.  Major cytogenetic response was achieved in 25 percent of the patients, and CHR in 85 percent of patients.
   Accelerated phase patients achieved an overall hematologic response rate of 37 percent, and blast phase patients an overall hematologic response of 30 percent.
   Our survival data exceeds that reported in the literature, as stated by Dr. Nicolini."

Note also that one patient in AP actually went back to chronic phase, that is pretty significant.

(2):  Quote from Adam Craig of ChemGenex - Transcript of the meeting: "Let me now clarify the T315I status of patients enrolled in Study 202, which is the second issue before you today.  Before enrollment, the presence of the mutation was confirmed by hospital or commercial laboratory analysis for all 66 patients enrolled in Study 202.

Such testing for detection of the mutation is widely available in the medical community and used in the day-to-day management of patients, as outlined in the NCCN CML treatment guidelines. The protocol inclusion criteria required that the patient have the T315I Bcr-Abl gene mutation.  At the request of the agency, the laboratory reports

documenting the presence of the mutation were recently submitted. The role of the central laboratories was to quantify the level of the mutation at pretreatment and during the study.  Central laboratory data was not attained in all patients pretreatment due to logistical and sample handling issues."  Trey you might recall that there were 11 countries included in this trial making it a logistical nightmare for any central laboratory.

(3): This is very critical, the point is that unless we get further clarification from the FDA, potentially every other drug in the pipeline now, will have to overcome this very same hurdle.  Quite simply, there is NO standardize test for Karyotyping.  NO standardize test for FISH.  NO standardized test for PCR.  And, there is NO standardize test for mutation testing.  Yet our doctors rely on them every day, indeed every drug available on the market currently was approved on the basis of how patients responded to treatment milestones from assays done with these non standardize, non FDA approved test.

More to the point, you should have been with me at the FDA and with the two patients who are being treated on this drug who were with me.  Both patients were on this drug for quite some time.  They have achieved a CCR - they are in the group of the 25% of the patients who have achieved this response.  But this isn't 25% to them - no, indeed it is 100% to them.  They have bought precious time, for one of the patients it was the time to see her grandchild be born.  There was nothing available for this patient at the time, there is nothing available at this time either.  You had to see these patients, sit down with them, eat a meal with them and yes Trey, I even prayed with them.  They are my heroes.  They have been to the scariest place we can ever imagine.  They have stood at the edge of the abyss and through the grace of science, we, in all our humanity have pulled them back, have rescued as many as we could, and we are devastated each time we lose even just one patient

Trey, we are all at risk.  I was humbled by their bravery.

I have no problem with stating that if it were me, I would gladly take this 25% and make it my 100%.

As for the other drugs in the pipeline, have you seen the data?  I have.  Not surprisingly, not all patients are being helped with the other drugs.  This is just a fact, we are not a one size fits all.

As per Jane Apperley's comments - 40% of patients will become resistant to Gleevec in five years.  Some of those patients will go on to respond to either Dasatinib or Nilotinib, but others will not, these patients will go to trial or request compassionate use, for the time being, of Omacetaxine.

Did you know that there are over 500 deaths in the US a year directly related to CML?  Did you know that many of these patients are in their 40's and 50's?  Average life expectancy in the US is 78.2 years - these folks are dying prematurely.

From my perspective, I want my doctor to have access to every tool and weapon in their armamentarium.

This is not about whether the FDA did a wrong to a company.  This is about a pivotal question for all of us, and the absolute need to get clarification on it.

If we had hit it out of the park every time we came out with a drug, we wouldn't be here.  The National CML Society in the US as well as the CML Society of Canada would be the historical societies of CML. Personally, I think that has a great ring to it - may it indeed be that in our lifetime.

Cheers!

Cheryl-Anne

Message was edited by: cherylanne

[PhilB]

Hi Cheryl-Anne

Could you clarify that extremely scary comment about "60% of patients will become resistant to Gleevec in five years".   Is she talking about only a subset of patients or all CML patients?  If the latter then that seems very much at odds with the usually quoted figures from IRIS etc.

Regards

Phil

[cherylannes]

Hi Phil,

Typing late at night, I flipped the number around, my brain was thinking 60% do not fail Imatinib (which is a good positive thought), versus the 40% who do fail Imatinib (according to the IRIS study), however, I mixed the numbers when I typed.  Jane Apperley was talking about the fact that 40% of the patients on the IRIS trial were no longer on Imatinib 5 years out.  She went on to say that at Hammersmith, with 200 patients they found it was around 37%, but in the community setting, from Northwest England, they found that 49% failed to achieve a complete cytogenetic response in two years.  Sorry for the confusion, I have to say it scared me when I got your email this morning - Phew!  Glad we cleared this up.  It was an honest typo and I am very glad you found it and we could fix it.  Thank you.

Best Regards,
Cheryl-Anne

Here is the quote of what Dr. Apperley is saying directly from the FDA Transcript. " Unfortunately, a significant minority of patients fail imatinib and recent data have provided useful information as to the extent of this problem.  For instance, in the pivotal study of interferon versus imatinib, known as the IRIS study, 40 percent of the patients randomized to receive imatinib were no longer receiving the drug 5 years later.
   In my own institution, a similar group of newly diagnosed patients totaling more than 200, a 2 proportion of them, 37 percent, had also failed imatinib five years later.  And actually, this figure may be higher in the community, as shown here by this population-based study in northwest England, where 49 percent of the patients failed to achieve a complete cytogenetic response at 2 years in contrast to the 20 percent in this situation in the IRIS study."

[Trey]

OK, so I see my stats are accurate.  Just wanted to make sure I was not stating them incorrectly.

I did not say the drug should not be approved.  But if it is approved, a patient and Onc would need to assess the risk of using what the FDA has called in their report a "low efficacy" drug vs the other available options, including BMT.  The clinical trials are designed to prove the effectiveness, and the FDA appears to have some reasonable questions based on those trials.  But that does not mean the company cannot answer those remaining questions and obtain approval for the drug after those questions have been answered.  A petition will not answer those questions.

[cherylannes]

Hi Trey,

With all due respect, you are entirely missing the point. The point is about the sudden change in policy by the FDA to question assay testing for this disease category.  Do you understand that until this quesiton is resolved, potentially no other drugs will come to market -- this is what the petition is about.  Please read the petition carefully.

Regarding your questions about efficacy - which is not what the petition is about, but I am endeavoring to answer your questions.  First and foremost, read the transcript from the FDA proceedings.  They are available publicly on the FDA website.  The majority of the voting members on the panel stated at various times during the proceedings, that indeed we are talking about a patient population that has a very poor prognosis, and this drug did show clinical efficacy for this patient population. Furthermore, they stated that if they had been allowed to vote on the clinical efficacy of the drug (which they were not), they would have voted to bring the drug to market. Why? Because it is well understood that this drug does have a clinical benefit for this patient population.   Clearly stated, the FDA did not vote on clinical efficacy. They voted on the test not being standardized

Let's talk more about this particular patient population.  Note that this patient population has had disease for varying lengths of time, the disease has not responded well to ANY therapy.  This includes pre TKI therapy such as Interferon, Ara-C and standard chemo. Further note, until Omacetaxine patients harboring this mutation were very often put back on to these treatments because treatment with a TKI actually selects for the mutation, we saw this clearly in the early phase I & II studies of Dasatinib for example. Clearly these other options were not helping these patients. The situation is that this is a patient population with a very form of stubborn, sometimes aggressive disease.  That there is response in this patient group is a real benefit.  Some may say, yeah, but you could put the patient back on to hydroxyurea.  Well yes you can, but no patient on that drug had any cytogenetic response, that I am aware of.

You say, that the drug should come to market,  "But if it is approved, a patient and Onc would need to assess the risk of using a relatively low performance drug vs the other available options, including BMT."  I agree that it is always up to the doctor and the patient. Given a patients information, it just might be that Omacetaxine is the drug for them to try.  At least there are options for the doctor to discuss. Providing options is what this petition is about.   Given the well known facts that this patient population have a particular form of CML that has serious unmet needs with regards to treatment options, can you indicate to me what you deem to be acceptable as per the level of performance in this particular patient population?  Furthermore, note that there is a very high number of patients in this patient population who are no longer candidates for BMT.  We who are younger with CML are not in the majority of the patient population with this disease - this is supposed to be a disease of the middle aged. 

As a side bar,  I was pretty excited to see that Omacetaxine does kill Quiescent CML stem cells.  Who knows what the future potential of this drug could be.  I do know that once it gets to market, clinicians and researchers are more free to try it in a variety of settings and explore it's full potential.

The petition is about the fact that there are currently NO STANDARDIZED tests in use at the moment to either diagnose, or monitor treatment milestones including detecting mutations such as T315I and the slew of other mutations we have encountered.  That is what the petition is about.  And yes, we believe very firmly that a petition is exactly what is needed in this instance.

As I write this there are 365 signatures on the petition.  They have been accrued in less than 48 hours.  We are pretty pleased with this, but every signature counts at this point and we definitely want more.

To everyone reading this - this issue is critical - we need everyone who has CML or knows someone with CML to sign this petition.  This is a critical question for all of us and we all need clarification.

http://www.petitiononline.com/mod_perl/signed.cgi?FDAOMACE

[srcarrow]

Thank you Tracy...I saw a few of your posts and could not help but reply....I was dxd with the mutation 3 1/2yrs. ago and have had CML for 11+ years, never thinking I would develop this dreaded deadly mutation but I did and here I am after trying everything and thank god for Chem-Genex....I spoke at the FDA-ODAC was with Cheryl-Anne and another CMLer...it was the most disheartening thing to experience....I don't know how a few of those people could go home and sleep that night let alone other nights....we are just US but we are so damn important at least my 3 grandson's think so and that's all I need that is all anyone should NEED....So thank you again...and I hope you never need to experience what we who have had!

Be Well,

Susan

[td1961]

Removed by poster due to privacy concerns.

td1961

[Trey]

Phil,

The overall disease progression rates among IRIS (Gleevec) participants at 5 years was 18% over the 5 year period for chronic phase participants.  This included not just resistance, but all forms of disease progression.  As someone who is a math whiz, you understand that averaging the blast phase patients with the chronic phase patients does not present an accurate picture. I would not want anyone to think the probability of Gleevec resistance is 40%.

"per the benchmark IRIS trial of chronic phase patients  with primary imatinib therapy,  the rate of all progression events, including cytogenetic  and hematologic relapse within chronic phase and  transformation to advanced phase, is 18% after a median of 5  years. However, such events appear to be most evident in the  first 3 years of treatment in the IRIS trial"

"for patients with  advanced disease treated with imatinib as salvage therapy,  rates of resistance and relapsing disease is dramatically  higher, occurring in 75% or more of AP patients and 95% of  myeloid BC patients."  Many of these patients were already quite ill after various other therapies failed (i.e., "salvage therapy").

http://asheducationbook.hematologylibrary.org/cgi/content/full/2006/1/219

[cherylannes]

This is information from an interesting slide that was presented at ASH.  You will also see it shortly on the video that will be posted on the CML Society of Canada's website from Dr. N. Shah's visit with us a few weeks ago.

What Happened with the IRIS patients ?

O'Brien SG. et al., Blood (ASH Annual Meeting Abstracts) 2008;112: Abstract 186

553 patients randomized to receive Imatinib.

1.)  322 patients still receiving study Imatinib = 60%
Of those 60%, 317 patients or (57%) achieved CCR and 15 or ( 3%) have not achieved CCR

2.) 221 went off study (40%) - but note some of the patients may have continued on Imatinib, they just did so off the study.
A) Of those 43 (8%) stopped for safety reasons, 17 of these patients (40%) are alive, 26 of these patients (40%) are dead (includes primary reason for stopping the study being death, n=13)
82 or 15% stopped the study for efficacy reasons, and of these patients, 52 or (62%) are still alive, 30 or (37%) are dead.
C) 96 or 17% stopped the study for other reasons, of these patients 81 or 84% are still alive, and 15 (or 16%) are dead.

It would also help us to define resistance.  Some respected CML experts define primary Imatinib resistance as failure to achieve a CCR by 12 months.  However, as we have seen with the IRIS information, patients who have not achieved a CCR are still enjoying progression free survival.   As Dr. J. Radich pointed out in "How I monitor Residual Disease in chronic myeloid leukemia, Blood 2009; 114(16):3376-3381 "MMR was the measure associated with the lowest incidence of progression beyond the chronic phase"

Do not get me wrong, in the cancer world this is clearly a home run on all fronts. We are all grateful for this, the improvement over IFN was phenomenal.  But, this data shows that we are not out of the woods.

I will be at ASCO next week and I will see and hear the presentations for all the front line data for both Dasatinib and Nilotinib.  As we know already, these second generation TKI's are clearly reducing minimal disease more substantially. 

[PhilB]

Oh what fun you can have decoding the results of clinical trials.  It never ceases to amaze me the layers of obfuscation that get built into some of them and the difficulty of getting to the answers you want.  I'd love to get hold of the raw data from the IRIS trial and others and have a really good root around.

The '40% no longer on Imatinib' = 'it only works for 60%' is a great case in point.  To try to get a 'what are my odds' answer out of that you need to exclude the people who left study for 'other reasons' as this will include people who died of something unrelated, moved away or just got fed up with being in a trial with all the added restrictions (eg no complimentary medicine allowed).  Of those who moved for efficacy reasons there are probably also some who had a 'good' response on G, but moved to another drug in hope of a better one (IRIS shows that sustained CCR is as good as MMR, but many people now will be moving drugs if they don't get MMR) and many other poor respoonses will be self-inflicted through poor compliance.  Take out all those factors and the numbers are much more encouraging.

.

On the other hand the headline IRIS numbers of percentage progressing to AP or BP is misleading as there is a time lag - often of many years - between poor response and progression. Other studies do things like reporting 'best response' (ie ignoring relapse!) or counting as 'non-CML deaths' people who don't survive the transplant process.  The bottom line is that you basically can't trust any puiblished statistic unless you know exactly how it has been arrived at.

The most useful statistic of all for me coming out of this discussion is the number of CML deaths per year in the US.  I believe I've previously seen quoted 5,000 new cases of CML per year in the US so if 5,000 are getting it and 500 are dieing of it then that's a fairly simple (and encouraging) sum.  Even then you can't just say 'I have a 90% chance of outliving this disease' as patients in AP or BP at diagnosis will be disproportionately represented.  For a newly dx CP patient with access to the drugs it may well be more like 95%.

None of this takes anything away from the need to get new drugs and treatments developed to deal with the remaining patients, and particularly to find something better than the transplant lottery for BP patients.

I'll be offline on holiday for the next week or so.  Best wishes to all

Phil

[cherylannes]

Interesting points to ponder Phil - thank you very much for your insight.

I would love to see the IRIS raw data myself - did you notice that the information provided in my post above from the IRIS 7 year update is missing 10 patients?  If you count the dead (71) and alive (472) we get 543, but we started out with 553 - we lost 10 patients somewhere.  So, survivability from this data is either 87% or 85% - still great.  Remember these were "de novo" patients, newly dxed, not on other treatment.

The question remains - "what do you want for yourself as a patient?" (1) CCR or even MMR = highly unlikely to be able to stop the drug   (2) CMR (or PCRU) maintained for a few years = likely to at least entertain the thought about stopping the drug (for now) (various studies support this, just peruse the ASH abstracts).  Dr. Talpaz feels that combo's such as Gleevec & INF (Interferon) or Sprycel & INF might possibly lead to 85% of patients stopping the drug.  He has announced expanding his clinical trial and has received significant funding from Novartis recently to support it.  See the thread of comments about this on www.newcmldrug.com

Who wants to stop the drug?  (1) if you are a younger patient - push the envelope, do not settle - get more aggressive with your disease (Dr. N. Shah favors this approach, and I have to say, so do I). (2) Long-term side effects (SE's) become debilitating after a while, even grade 1 & 2.  In our (The CML Society of Canada) pivotal survey in 2008 we found out that of the patients that responded 67% reported the SE impacted their social life, 77% said that the SE impacted their work life and 72% impacted family life.  74% of the patients reported that the cost of treatment represented a serious financial burden.  All of these factors seriously affect adherence, which then has a serious affect on how well the drugs perform, that is why it is not surprising to see  that in a community setting there were 49% of patients who showed signs of resistance (as per Dr.Jane Apperley).

Who are less inclined to want to stop drug therapy? (1) patients not being bothered by SE's (2) Patients not being troubled financially (3) Patients who are mid sixties or older as the average life span is near 80 years.  Very highly likely that current treatments will equal normal life span for these patients. 

There is of course a caveat; it depends on your disease stage, CP patients fairing the best.

Overall survivability is greatly improved.  However, there are clear unmet needs on all of these other areas addressed here. 

Enjoy the holiday!

[Trey]

Cheryl-Anne,

Would you kindly provide a reference to your Gleevec statistic:

"it is  not surprising to see  that in a community setting there were 49% of  patients who showed signs of resistance (as per Dr.Jane Apperley)."

I have not been able to find it, although I have read her articles.  And it is far different than the statistics reported elsewhere.  Thanks.

[cherylannes]

Trey,

From the FDA ODAC meeting transcript which you can access off of the FDA website - and you should go peruse it....

Page 31 & 32:

"So how have these drugs changed the outlook for this disease?  In contrast to this inevitable triphasic pattern with interferon, hydroxyurea and busulfan that I showed you earlier, the great majority of patients taking imatinib achieve a complete cytogenetic response and enjoy a chronic phase which is predicted to be at least 12 years and may actually be for the duration of the life of the individual.
   Unfortunately, a significant minority of patients fail imatinib and recent data have provided useful information as to the extent of this problem.  For instance, in the pivotal study of interferon versus imatinib, known as the IRIS study, 40 percent of the patients randomized to receive imatinib were no longer receiving the drug 5 years later. In my own institution, a similar group of newly diagnosed patients totaling more than 200, a  proportion of them, 37 percent, had also failed imatinib five years later.  And actually, this figure may be higher in the community, as shown here by this population-based study in northwest England, where 49 percent of the patients failed to achieve a complete cytogenetic response at 2 years in contrast to the 20 percent in this situation in the IRIS study." 

Some similar data was discussed at ASCO in 2008 the UNIC study: http://www.asco.org/...bstractID=33049

Now off to the weekend....