provenge

I sugest everybody knows good news about Provenge in Europe. European Commission (EC) has granted marketing authorization for PROVENGE. The marketing authorization provides approval for the commercialization of PROVENGE in all 28 countries of the EU as well as Norway, Iceland and Liechtenstein


"With sipuleucel-T, we have the potential to create a new treatment paradigm in advanced prostate cancer, with the integration of this novel therapy to harness a patient's own immune system to fight their cancer," said Prof. Karim Fizazi, M.D., Ph.D., Head of the Department of Cancer Medicine, The Institut Gustave Roussy, Villejuif, and Full Professor in Oncology, the University of Paris, France

All countires within EU has to ''give the Option of Provenge'' to OFFER it to patience as per EACH INDIVIDUAL National Health System. Their doctors don't depend from money and perks of big pharma as in USA. I hope Provenge will become really first in line and fundation of treatment for mCRPC :

more progressive view of immunotherapy/disease treatment inside European medical circles, few if any reimbursement type issues, and population density making the process more accessible to patients.

I firmly believe other cultures will respect the low side-effects and concept of immunotherapy as superior...and accept it first.

Meanwhile Ipilimumab (Yervoy) fails to show overall survival benefit in mCRPC after chemotherapy. Median overall survival (OS) times were 11.2 months for patients treated with ipilimumab and 10 months for patients treated with a placebo.The difference OS for patients in the two arms of the trial was not statistically significant (hazard ratio [HR] = 0.85. It it is clear that the potential value of this drug for most men with mCRPC who have failed chemotherapy is low in the extreme. Very sad. Still there is trial with Ipilimumab in prechemo setting. Result expected in the end 2015.

Dr. Shore , the Medical Director of the Carolina Urological Research Center, as well being on staff at the Grand Strand Regional Medical Center said :"We have several other very interesting immunotherapies that are out there... but it works differently from Provenge, as does ipilimumab, prostvac. These are different mechanisms of action. What I love about that is these different immunotherapeutics, they’re not going to me-too drugs. It’s not Bayer versus Anacin aspirin. These are immunotherapeutics that are designed to re-stimulate, better involve our native immune system by going at it at different pathways. So isn’t that exciting if you have advanced disease that you could have not just one but two or possibly three other ways of stimulating one’s immune system to fight the cancer?.. It’s about staying alive with good quality of life and being able to do the things that one worked hard to do in one’s life. It’s a great time."

What I think untargeted to an antigen immunotherapy isn't going to work in PCa. It is one of main reason why I skeptical about success for Prostvac and Ipilimumab in PC. Time will show.

Meanwhile Ipimulimab is almost twice expensive then Provenge and it isn't personal medicine, you don't need alter it to every patient. For example according to University of Utah hospitals and clinics price per 4 doses regimen for Ipimulimab is $ 172,800. If Dendreon put such price for Provenge they could solve all their financial problems.

pharmacyservices.utah.edu/bulletins/NDB_231.pdf

I found this to be an interesting discussion on Provenge, apologize if posted elsewhere...

www.onclive.com/peer-exchange/crpc-cases/Treatment-With-Sipuleucel-T-in-Advanced-Prostate-Cancer

RobertC said: "Will European health authorities pay much for Provenge treatment?"]

I don't think Provenge will have problem. Ipilimumab (Yervoy ), immunotherapy for Melanoma have been recommended for use on Britain's state-run health service.The price of a four-dose course of Yervoy, which is recommended only for people who have received prior chemotherapy, is 75,000 pounds = 120,000 $.


RobertC said :" Dendreon is in debt and losing money in the USA"

I guess we all got a rude awakening considering the history in the dirty dealings against Provenge that its not about what is wrong or right but greed and corruption whether we are talking Pazdur M.D.,Von Eschenbach M.D. FDA, BP, Milken.....you just name them......the almighty buck before good medicine and patient welfare first and foremost. Too bad for humanity. Sad to say but a very screwed up world we live in.

Tragedy of Provenge always will associate for me with this photo of 3 good friends who plaid and I believe continue to play crucial role to limit access to this revolutionary treatment to PC patients:

www.mikemilken.com/photos.taf?photo=116


Those of us who know the SCIENCE behind Provenge know that patients must receive and it should be if the patient's BEST INTERESTS are followed. That's right. If you want to hit him with the BEST treatment to keep him alive as long as possible so hopefully he dies from something else!

In recent Conference of European Society for Medical Oncology ( ECCO 2013) the most sound message was: right of every patient w/ cancer to have the most appropriate treatment & care for their disease.

I hope Europe will do it right and many PC patients will benefit from Provenge.


RobertC said:" Will another company have to come forward to partner on the commercialization of Provenge in Europe?"

At first Company has manufacture partner that will make Provenge: PharmaCell, The Netherlands.

I more convince now it will be no partner for selling drug, it will be ''dirty" buy out or company will be driven to bankruptcy. It will be miracle if Dendrion will stay independent.

What will happened: or Provenge will become foundation of care for HRPC ( after the biggest robbery buy out in history ) or it will be put on the shelf like Bexxar therapeutic for lymphoma, by GlaxoSmithKline ( stop revolutionary treatment).

journals.lww.com/oncology-times/Fulltext/2013/09250/Lymphoma_Specialists_Lament_the_Discontinuation_of.3.aspx


Adjust,

Thank you for interesting video.

My take from that discussion:

three randomized, placebo-controlled, multi-centrer Phase III studies for Provenge demonstrated we have OS;

first in class very-well tolereted treatment take only 1 month;

Need new surrogate biomarkers, hope will have them next 5 years, meanwhile I posted about new biomarkers for Zytiga several days ago:

www.healingwell.com/community/default.aspx?f=35&m=2869653

no response on PSA but some people can see redaction (25-30 % of patients from last phase 3 Impact trial );

Different approach for using Provenge:

Evan Y. Yu, MD.believes after Provenge, scanning should be delayed for 6 months or until symptoms occur, as the disease may appear worse initially. After 6 months, switching to a new therapy may only be warranted for patients with rapidly progressive disease.


Mark C. Scholz, MD, administers Provenge as soon as metastases are detected followed quickly by Zytiga or Xtandi. Scholz utilizes eplerenone (Inspra) in lieu of prednisone in combination with Zytiga, to address concerns over adverse reactions with sipuleucel-T(Provenge).
This approach seems safe and effective and addresses the issue of not being able to detect progression via PSA .
If give Zytiga first - can lose valuable time window for Provenge. So Provenge first -after immediatly withing 1 month Zytiga.


What caught my attention:

Dr. Evan Y. Yu said he even show Kaplan Meie surviver curves of patients treated with Provenge from last final trial. You can see split beetween Placebo and Provenge start in 6 months. You can see it here ( p.13):

www.dendreon.com/prescribing-information.pdf

You can also look at Figure 3 ASCO 2011: Poster Prolonged Survival in Control Arm Provenge presented by Dr. L.G. Gomella:

Post-Progression Treatment with APC8015F may have Prolonged Survival of Subjects in the Control Arm of Sipuleucel-T Phase 3 Studies. Look at Figure 3 :

Blue line Sip-T (Provenge) median survival time-25.4 months;

Green dotted lime APC8015F (Frozen Provenge) median survival time- 23.5 months;

Red dotted line Placebo median survival time-12.7 months;

Difference between Provenge groop and real Placebo without crossover- 12.7.

Conclution: APC8015F (Frozen Provenge) may have prolonged survival of the control arm in the three phase 3 stadies of SP-t ( Provenge), potentially diminishing the observed survival benefit.

www.scribd.com/doc/73051542/ASCO-Poster-Prolonged-Survival-in-Control-Arm-Sip-T-Gomella-2011


Now let see Kaplan Meier survival curves of patients treated with ZYTIGA before Chemo ( Zytiga is prescribed in the same space that Provenge: before chemo);

www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002321/WC500112858.pdf

on the page 12 figure 3 Kaplan Meier survival curves look very strange : patients presumably have to take it for 14 months and then, wait 4 more months to determine if there was a life extension benefit (OS). Curves did not separate until the 18th month...4 months after patients in the treatment arm came off the drug. It mean you need take Zytiga for 14 months + wait 4 months before you will have better chances to be alive longer then person who didn't take Zytiga. Of concern, as well, was the fact that 69% of patients in the treatment arm (Zytiga + prednisone) discontinued treatment at the time the trail was stopped (versus 84% of patients in the placebo + prednisone arm).

So Zytiga didn't meet prespesified value for statistical significance OS ( HR- 0792; p-0.0151). The famous biostatistics expert Dr. Susan Halabi was selected by ASCO 2012 to present on the data and in her presentation said:Zytiga pre-chemo was a"failed trial"( because fail OS) She presented a chart showing the statistics and on one side was the category "effective" and on the other "ineffective" and although it was close, Zytiga was labeled "ineffective":

www.xconomy.com/national/2012/06/03/jj-prostate-cancer-trial-shouldnt-have-been-stopped-early/

Meanwhile Provenge is currently the best-performing drug (in terms of overall survival hazard ratio).


49packard,

I hope your cancer stay in bay and progressing very slow.

My best to all of you,

Hope

Post Edited (HOPENEVERDIE) : 10/7/2013 1:14:57 PM (GMT-6)

On 10/28/2013 Urotoday posted :"The Immunotherapy for Prostate Adenocarcinoma Treatment (IMPACT) trial: Lower baseline prostate-specific antigen Is associated with a greater overall survival benefit from sipuleucel-T, "Beyond the Abstract," by Philip W. Kantoff, MD.

This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.":

BERKELEY, CA (UroToday.com) - The phase III IMPACT trial (Immunotherapy for Prostate Adenocarcinoma Treatment; D9902B; NCT00065442) showed that sipuleucel-T treatment in men with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC) significantly increased survival and reduced the risk of death by almost 23%. The results of this pivotal trial supported the approval of sipuleucel-T for the treatment of patients with mCRPC by the US Food and Drug Administration.

We recently reported retrospective subanalyses of the IMPACT trial, which explored the potential predictive value of baseline variables in patients treated with sipuleucel-T vs control. An overall survival (OS) benefit was observed with sipuleucel-T across all subgroups based on the baseline variables used in the Halabi score (prostate-specific antigen (PSA), lactate dehydrogenase (LDH), hemoglobin, Eastern Cooperative Oncology Group performance status (ECOG PS), alkaline phosphatase, and Gleason score); however, a trend towards a greater magnitude of OS benefit was observed among patients with better baseline prognostic characteristics (in particular, PSA and LDH values at or below the median and ECOG PS 0). When patients were further subdivided into quartiles by baseline PSA, we found that those with lower (≤ 22.1 ng/mL) versus higher (> 134 ng/mL) baseline PSA values not only generally lived longer, but also achieved a greater benefit with sipuleucel-T. The estimated improvement in median survival with sipuleucel-T vs control was 13.0 months in the lowest baseline PSA quartile and 2.8 months in the highest quartile. Furthermore, the risk of death for patients in the lowest baseline PSA quartile was reduced by 49%, compared with 16% for patients in the highest PSA quartile.

Although retrospective, the subanalyses reported in Urology together with the primary IMPACT analysis suggest that patients with less advanced disease – particularly those with more favorable baseline factors such as low PSA – may benefit the most from sipuleucel-T treatment, and provide a rationale for immunotherapy as an early treatment strategy in sequencing algorithms for mCRPC. Indeed, patients with a lower disease burden may have a more robust immune system due to less tumor-mediated immunosuppression and fewer prior immunosuppressive treatments, as well as having more time to allow the immune system to mount an effective response. Other active agents in mCRPC treatment (docetaxel, abiraterone acetate in the pre- and post-chemotherapy settings, and enazlutamide in the post-chemotherapy setting) seem to work reasonably effectively independent of tumor burden as measured by PSA. Again, these retrospective findings suggest that earlier implementation of sipuleucel-T should be considered. Patients with more advanced disease may not derive much benefit. New immune biomarkers that are tied to the mechanism of action of sipuleucel-T hold promise to identify those patients with the greatest potential to benefit from an immune-based therapy. Until such markers become available, disease burden as represented by baseline PSA appears to serve as a useful marker to integrate into a clinician’s assessment of therapeutic options for patients with mCRPC.

www.urotoday.com/Prostate-Cancer-Immunotherapy/the-immunotherapy-for-prostate-adenocarcinoma-treatment-impact-trial-lower-baseline-prostate-specific-antigen-is-associated-with-a-greater-overall-survival-benefit-from-s.html

MY best Hope

Post Edited (HOPENEVERDIE) : 10/30/2013 12:36:11 PM (GMT-6)

Mr. 49 PACKARD

I congratulate you for your decision in changing medications. I think that you would have done well as much with something else other than Provenge during these 14 months of PCa treatment.

I also want to thank you for taking the time along to share with the many your experiences with Provenge. At the end it didn’t cure you but it didn’t harm you too, and as we comment in Portugal when not sure of what to do, we customarily say “what doesn’t kill makes it fattening”. A win-win strategy with no harm. 

Contrary to what many may think, countries within EU are not obliged to accept Provenge as part of the treatments provided in or by their National Health Systems; In particular, if such a therapy is more expensive or can be substituted by others with proven results on the run or cheaper. In general, treatments are done at the National Health Facilities with no charge to patients. However, when the treatment is done at private clinics, the patient will have to pay the total bill from his pocket upfront, receiving later a partial refund based on limits pre established, which are typically the cheapest ways to treat the disease. Usually the amount covered is lower than the cost of a similar treatment at the National Health System.

In 2013 there has been much fuse in Europe about Immunologic therapies. Most of the euphoria was a cause from a decision by the shareholders behind Provenge to spend 25 million in advertising programs. Almost all TVs in all the countries have broadcasted something about the treatment, some of them quite nasty. The Portuguese TVi presented a documentary which was greatly opposed by the medical community. The contents were very untruthful and the doctors used as panellist of the program were simple figures in the oncology community. Much more efforts must be done if Provenge wants to do better in Europe.

I hope Zytiga is “friendly” to you and that you find the peace of mind you so deserve.

Best wishes.

Baptista 

49,

Thanks for keeping us updated on your Provenge journey. Zytiga has shown amazing results as well...

Were you on any hormone therapy drugs throughout your Provenge use....Lupron? Casodex? Avodart?

Thanks again...
Jerry

How about Casodex?