provenge update

Todd,

Is there anyway you can at the very least get a new Urologist within the Kaiser network? We have Kaiser and I can't say enough about my hubby's team. I understand our situation is different from yours, but can say his team of doctors were nothing short of amazing. They are young docs,eager to help, extremely knowledable, compassionate, passionate and ALWAYS responsive. Most days his docs were returning our emails within a few hours, and we sent many. We felt so very taken care of by this team. Hubby's GP, well she's a different story. She isn't on top of the lastest technologies and information about PC and its treatment. We will have decided to find a new GP for hubby and will start by asking his urology team for referrals.

Anyway, I know this may not help get you Provenge, but I think it makes a world of difference to know your team of Urologist are top notch and really in your corner.

Jerry,

Exactly. Better than what he currently has.

Todd, I come to this thread each day to see if any progress is made.  So, you fired your doctor who is on vacation?  Did you get a new doctor?  I hope you get an answer sooner than later.  You are very determined and I wish you success!

Welcome Hudson 1959!  I hope you will come back to visit.  Also, may your husband's PSA be near zero.  Wishing him the best!

Aimzee

Regarding the matter of Kaiser and the reference to people younger than 65 and their response to Provenge, Kaiser is referencing a junk science paper that has repeatedly been debunked. The paper was written by Marie Huber, et al., and it is specious. I have asked two people knowledge of the paper and the science to comment. Here are the details:   Interdisciplinary Critique of Sipuleucel-T as Immunotherapy in Castration-Resistant Prostate Cancer Marie L. Huber, Laura Haynes, Chris Parker, Peter Iversen http://jnci.oxfordjournals.org/content/104/4/273.full.pdf   Here's Ocyan's response: The entire thesis of Provenge not working or even harmful was inspired by a single odd-looking data points in the FDA Clinical Review on the effect of Provenge when measured on the subgroups of patients <65 and >=65 years old. This is much ado about nothing. Here are a few observations: 1. When as many subgroup analysis are performed as in the case of the FDA Review, there bounds to be some analysis that would go in the opposite direction of others. This is because there are an exponential number of subgroups (for a population of N patients, there are 2 to the Nth distinct subgroups) and it is impossible to guarantee that every one would be balanced with respect to the relevant prognostic factors. 2. The <65 subgroup had 106 patients on the Provenge arm vs 66 on the control arm. The trials were enrolled with a 2-to-1 randomization plan and 106 is not anywhere near twice 66. Trial arm sizes are most basic; yet, randomization failed to balance them! This means that various important prognostic factors (relative age, bone mets, ECOG, etc.) were likely out of balanced too. At this point, any analysis of this subgroup must be taken with a very large grain of salt. 3. Of course, the >=65 subgroup is just the complement of the <65 group so all observations above applied to it in the same way. 4. For some evidence of why the analysis of the subgroup <65 in the IMPACT trial may be suspected, consider the FDA analysis of the patients <65 in the D9901 trial. In that case, the result was a median of 35.2 months for Provenge vs 28.2 for control. At the surface, this analysis indicated that the <65 D9901 patients were healthy and Provenge worked great on them yielding a 7 months median advantage. This finding directly contradicts the finding for the same subgroup in the IMPACT trial. 5. The FDA performed an age-related analysis based on the two subgroups above median age and below median age. To be clear, this analysis divided the total population into two equal size subgroups, one above median age and one below. Then the two subgroups were analyzed separately to see if there were any drug effect across the treatment and control arms. The results said yes, Provenge worked! 6. Lastly, the FDA, in fact, did a large number of sensitivity analysis of the Provenge data submitted in the BLA and clearly concluded: "Reviewer's comments: The exploratory pooled analyses in Table 14 (in the Clinical Review) were conducted across multiple studies to analyze the effect of age on the primary endpoint, overall survival. The above analyses of the data from all three studies (D9901, D9902A, and D9902B) support the hypothesis that the subgroup of subjects who were less than 65 years of age also benefit from treatment with sipuleucel-T. The hazard ratio in the subgroup of Study D9902B subjects who were less than 65 years of age most likely resulted from chance, related to the multiplicity of comparisons in 49 different subgroups." In conclusion, statistical considerations as well as far more extensive analysis done by the FDA showed that the anomaly seen in the analysis of subgroups <65 and >=65 quoted by the JNCI paper was likely a fluke event due to statistical fluctuations instead of some inherent problems with how patients were treated on the control arm. The rest of the paper consisted of more tenuous hypothesis made up to explain that misconception. Nonetheless, it should be pointed out that the hypothesis that the immune system of older patients was somehow damaged by the placebo protocol was sounded rejected by Dr. James Gulley, Director of Clinical Trials at the NCI, at the conference to review Provenge organized by the Center of Medicare Services in 2010.   And here's the MD's: Your penchant for requiring a scientific phenomenon to have an explainable biological answer is woefully struggling when it comes to the ridiculosity of theorizing that taking WBC s out and not giving them back could explain the placebo groups bad outcome. Neutrophils only live for about one day, so they need to be continually made. Lymphocytes are released from lymph nodes at a rate that is estimated to be enough to replenish the blood supply 11x daily. If this ridiculous theory were true, trauma patients would not only receive red blood cells upon major blood loss, they would also have to have white blood cells infused. Your little story makes for good drama indeed, but please make sure you clearly label it as the fiction you intended it to be.   Ms. Huber and her co-authors have done the medical community and PCa patients a major disservice. To what end? That is the question. What is their agenda?

Sundance 2020 you seem most enlightened for a new member are you in the medical field? I am playing what's my line (lol), I suspect your incite gives way to wondering whom you are. Like your referencing and trying to help Todd and others in this mine field.

One last post, and then, I have to get my parrot ready for the night. (;>)

Marie Huber, writing for the Journal of the National Cancer Institute, claims that Provenge does not work for patients under 65 years old. (NOTE: The Journal of the National Cancer Institute is NOT at all affiliated with the National Cancer Institute and is instead a publication of Oxford Press.)

There are many who claim Ms. Huber has no qualifications to write such an article. Her last few jobs prior to embarking on her anti-Provenge crusade has been doing financial analysis for hedge funds (her resume: http://theprovengetrials.org/files/resume_marie_huber.pdf ).  Now you have Kaiser denying Provenge coverage to patients under 65, and urologists citing her article as a reason not to prescribe Provenge. CMS has already debunked her thesis.

Ms. Huber is listed as the first author, but many believe she is NOT qualified to write such a paper. So, who wrote it? And why?

Here she cites her motives for leaving her hedgefund financial job and undertaking her crusade against Provenge: http://theprovengetrials.org/files/why.pdf

The material above was taken from an Investor Village Message Board devoted to Dendreon:

http://www.investorvillage.com/smbd.asp?mb=971&mn=433465&pt=msg&mid=11520656

Be warned: the writer of the IV MB piece was more strident in his remarks. (Translation: he used four-letter words)

I hesitated providing this information because some would say it is biased. But if an appeal is being prepared or a complaint is to be filed with the authorities, then it's best to go in with everything you have on the first submission and let the authorities sort it out.

You be the judge. Does Huber's paper quack like a duck?

Sundance

Todd you probably got some huge incite to it all now bro, I didn't read all that as of yet but very impressed with Sundance's depth of incite. Sundance if you post any headlining topics on this forum, I will be eager to see what you have to say probably on anything. I love thought provocing, exposures of realities or agendas, the cashing in on patients that is obviously part of the program we face and any real truths that otherwise we would not obviously see. Patients in effect getting the shaft from various angles and may not even recognize it. Sundance how long have you been watching this forum, curious dude here????

(I am impressed)

Just read the link www.caretolive.com     (suggest others read the story about the delays on Provenge and politics envolved?). This is interesting to know what went on and that Provenge could have been out for patients earlier and whom was behind some of the delays...you will recognize the named envolved, I think.

The other link is a clickon event now here: http://www.minyanville.com/businessmarkets/articles/Dendreon-Provenge-safety-data-provenge-safety/5/17/2011/id/34592  

Thanks for all the info Sundance....you are the resident expert on Provenge for us on H.W
Totally agree with your advocacy thoughts.

Thanks, Jerry.

First, I have been following Medivation and MDV3100 for quite some time. it appears to be a very good medication, with a median life-extension benefit of 4.8 months. It is not yet approved by the FDA, but I would expect it to be, first, of course, for post-chemo patients. Eventually, it has the potential to be used for all PCa patients.

Zytiga, of course, already is available for use in the post-chemo environment. It is being prescribed off-label in about 20% of PCa cases in Provenge's space, but there, it has the second lowest rating from the bottom based on a limited Phase 2 trial. (Provenge, of course, has the highest rating in its space.) Zytiga must be used with prednisone, and so, because of de-tox problems, there are concerns regarding sequencing of Provenge and Zytiga. Dendreon currently is running a trial with JNJ to determine how Provenge and Zytiga should be co-administered. For now, the Journal of Clinical Oncology has this to say:

http://jco.ascopubs.org/content/29/27/3595.full?sid=a9e276db-0ac1-4ca1-8fd4-a16a19e7151f%23sec-14

"The practical dilemma of the appropriate sequence of use of the two new noncytotoxic agents (sipuleucel-T and abiraterone) is being addressed by trials that are under development. For now, given the broader window of applicability of abiraterone and the longer time required to develop an immune response with sipuleucel-T, if both agents are to be used, it seems reasonable to administer sipuleucel-T first with Abiraterone after additional disease progression. Biomarkers to help define the optimal use of immunotherapy are needed."

Frankly, as is the case with most cancer treatments, this is not an either/or situation. Most treatments will be 'layered on,' and in the case of PCa, it will be no different. Doctors will use everything available, at the appropriate time.

Finally, yes...annual PSA and DRE...my doctor is just thrilled LOL

Sundance

Sundance,
Your posts have confirmed a great deal that I had already suspected.I am a mechanic by trade and I have never been a hero. I believe that every man has a calling at some point in their lives that is much larger than the man himself. To quote spock. The needs of the of the few. I have decided to for go any other treatment in my quest for Provenge. It is my hope that success on my part will open the door for others. You have given me much information and I thank you. If I can help you in any way my email is at this site. I would allow myself to be the poster child for this cause. 48 years old. Stage 4 hard worker nice family. Just a thought. Probably a stupid one. I just dont want to see others go through what I am going through. Every successful campaign has a face. If it will help. Let it be mine.

Sundance,

Do you have an email address we could use?  I have an off the record question for you...

Thanks,

Jerry L.

At the risk of being a party pooper, I have one concern:

Sundance, you seem to have a financial interest in promoting provenge.

While I am totally supportive of Todd, I am still concerned that your posts might have a bit of a conflict of interest.

Is this appropriate here?

If I am totally off-base, others will let me know

I guess I am asking the MODERATORS for their opinions.

Mel

Sundance:

This is nothing personal and I'm just asking the question.

If nobody else has any questions/doubts about this line of posting, then it's fine with me.

Your posts have indeed been very informative and hopefully they will help Todd with his situation.

It just makes me a little uncomfortable regarding possible biases here.

Anyway, I've said my piece. I hope you will stay unless/until others see a problem

The moderators are strangely silent.

Mel