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Inergy, L.P. Message Board

wilderguide 326 posts  |  Last Activity: 41 minutes ago Member since: Jan 13, 2011
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  • Reply to

    Method of Treating Cancer & Bone Cancer Pain

    by wilderguide 2 hours 2 minutes ago
    wilderguide wilderguide 41 minutes ago Flag

    $$$$
    "It would seem that they do want to eventually market Cabo as a go to agent for treating bone metastases..."
    I have felt this to be precisely the campaign strategy for over two years now, and have been optimally gratified by the returns to date of the peripheral bone microenvironment biopsy, biomarker, and imaging studies. I'm convinced that - in the larger picture - Cabo will find far greater utility than salvage therapy...and the bone effect may prove more valuable than the anti-tumor effect. JMO

  • Reply to

    about some exhibits recently of exelixis

    by laoxao855 1 hour 14 minutes ago
    wilderguide wilderguide 1 hour 10 minutes ago Flag

    $$$$
    laoxao855
    1 post | Last Activity: 2 minutes 40 seconds ago
    Member since: Aug 22, 2014

  • Reply to

    Method of Treating Cancer & Bone Cancer Pain

    by wilderguide 2 hours 2 minutes ago
    wilderguide wilderguide 1 hour 43 minutes ago Flag

    $$$$
    For starters, try these two paragraphs on for size:
    "In another aspect, the invention provides a method for preventing bone metastases in patients with lung cancer, breast cancer, melanoma, renal cell carcinoma, or thyroid cancer, who have not yet advanced to metastatic disease, comprising administering a therapeutically effective amount of a pharmaceutical formulation to a patient in need of such treatment comprising Compound of Formula I or the malate salt of Compound of Formula I or another pharmaceutically acceptable salt of Compound of Formula I, to a patient in need of such treatment.

    "In another aspect, the invention provides a method for extending the overall survival in patients with lung cancer, breast cancer, melanoma, renal cell carcinoma, or thyroid cancer, comprising administering a therapeutically effective amount of a pharmaceutical formulation to a patient in need of such treatment comprising Compound of Formula I or the malate salt of Compound of Formula I or another pharmaceutically acceptable salt of Compound of Formula I, to a patient in need of such treatment."
    GLTA

  • $$$$
    US20140179736 filed 5/2/2012... Published 6/26/2014
    Gisela Scwhab, Dana Aftab, and Exelixis...
    My apologies if this a repeat, but there is soooo much information here I had to post it.
    Cancers, targets, preventive, prophylactic, and maintenance therapy. Lots of proposed uses, some of which I had prior only seen postulated on this message board. I've gotta admit, I was wowed to find this...
    GLTA

  • Reply to

    EXEL presence at ESMO

    by wilderguide Aug 8, 2014 5:16 PM
    wilderguide wilderguide Aug 20, 2014 8:57 PM Flag

    $$$$
    Not to make sport of the process, but it's the same with every P3 registration trial I've witnessed - and I'm sure it's the same for all the great many I haven't witnessed... The only folks interested in seeing a bunch a patients die so we can have trial results are the shareholders. JMO

  • Reply to

    Prednisone

    by csanderson1805 Aug 20, 2014 12:57 PM
    wilderguide wilderguide Aug 20, 2014 3:34 PM Flag

    $$$$
    Earlier this month, dimples orourke had some commentary wrt the use of prednisone in mCRPC (dimples suggested prednisone delivered OS benefit) and I went looking for current info on corticosteroid use in advanced CaP...toxicities, benefit, survival, etc. Guru Sonpavde, et al Feb 2014 That's' right, same guy that interviewed for the mRCC video. This post is a repeat.
    "We conducted a meta-analysis of randomized trials comparing regimens that included daily oral prednisone (P) in only one arm to investigate its impact on toxicities and outcomes in metastatic castration-resistant prostate cancer (mCRPC). Five trials were identified totaling 2939 patients, of whom 1471 were randomized to an arm not containing P and 1468 received therapy containing P. There was no difference between the non-P and P groups for severe toxicities (incidence rate ratio [IRR] = 0.82, p = 0.712, I2 = 97.9%). When examining toxicities as a reason for discontinuing therapy, the non-P groups were not different from the P groups (relative risk [RR] = 1.24, p = 0.413, I2 = 86.8%). The non-P groups demonstrated no difference in OS compared to the P groups (HR = 1.09, p = 0.531, I2 = 79.7%). The meta-analysis is limited by the trial level design and small number of trials."
    GLTA Less

  • Reply to

    WRNMMC Prostate Support Group newsletter

    by wilderguide Aug 20, 2014 5:56 AM
    wilderguide wilderguide Aug 20, 2014 6:41 AM Flag

    $$$$
    "We may expect more toxicity to occur in the Cabo treatment group as compared to the prednisolone group. If this toxicity is not balanced by a trend towards improved survival in the Cabo group the DSMB might not have consented to continuation of the trial."
    There is a delicate balancing act at play. Optimizing dosing for efficacy vs the imperative for liberal and timely dose reduction to manage AEs. It'll all boil down to that one simple question: Is the benefit worth the risk? Stay tuned...

  • $$$$
    Onclive 5/30/14. From the section describing the lifetime research achievements of Dr Philip Kantoff:
    "His work has led to the FDA approval of drugs for prostate cancer including the chemotherapies mitoxantrone and cabazitaxel and the vaccine sipuleucel-T.
    Kantoff played a vital role in the development of abiraterone and cabozantinib.
    He is chief clinical research officer and chief of the Division of Solid Tumor Oncology at Dana-Farber Cancer Institute." GLTA

  • $$$$
    From Walter Reed National Military Medical Center, dated February 2014, from the section on Prostate Research Progress found on page 17. This little blurb on Cabo tops the list, ahead of approval info for both RA-223 and Abiraterone.
    "Cabozantinib shows impressive activity in prostate cancer. This includes the disappearance of bone metastases on scans described as unprecedented. However, there were also adverse events seen at higher doses, and more research is needed, ASCO comments; larger phase 3 trials that will collect survival data are in progress. Cabozantinib (Cometriq), a multire- ceptor tyrosine kinase inhibitor, is approved for use in medullary
    thyroid cancer."
    GLTA

  • Reply to

    Comet1 question for Wilder

    by oncodoc02138 Jun 23, 2014 9:32 AM
    wilderguide wilderguide Aug 19, 2014 10:45 PM Flag

    $$$$
    "....if Comet-1 doesn't achieve statsig results it won't matter much, no matter how much we try to relate to the QOL issue..."
    The point of the discussion is not undermine the importance of overall survival, but rather to embrace that in a treatment algorithm that delivers life extension, there will be more opportunity for drugs that deliver hrQOL benefits. To put it simply, men living longer with CRPC will also need to live better. Pain relief may not be the only consideration.
    "I personally would never donate another penny to the PCF if they facilitated such a head fake."
    This is a point well-taken, and I would presume their strength of lobby will represent the cause in the event that an ADCOM is required to interpret a marginal - yet positive - result. The Comet-1 trial has the potential to test an integrated healthcare system like few others, and the strength of the hospice lobby may make a historic difference. JMO

  • Reply to

    Comet1 question for Wilder

    by oncodoc02138 Jun 23, 2014 9:32 AM
    wilderguide wilderguide Aug 19, 2014 3:41 PM Flag

    $$$$
    "All of the larger hospice care groups have sent letters to the FDA asking for approval."
    This would provide the assurances of a great post. Can you provide any research leads? I rather like where this is going, and see nothing but good in the prospect - if, at first approval in CRPC - Cabo gains major support based to large degree on hospice effectiveness. Cabo occupies an interesting therapeutic spot to consider, and if OS proves not statsig in the Comet1-defined patient setting, I still fully expect to see data delivery that indicates undeniable patient benefit underscored by a wealth of biomarker-substantiated patient benefit, including pain relief. An undeniable survival signal would come as no surprise, though statsig may prove impossible in this late-stage patient setting. Comet-1 is playing against a stacked deck of regulatory regimentation, and the hospice-effect consideration of Cabo benefit has been under-considered. JMO

  • Reply to

    Comet1 question for Wilder

    by oncodoc02138 Jun 23, 2014 9:32 AM
    wilderguide wilderguide Aug 19, 2014 1:31 PM Flag

    $$$$
    Hi Snowflake,
    Putting hospice care into regulatory perspective is a wonderfully compassionate overview of a treatment regime that has historically placed the heftiest premium on survival benefit. I think your commentary is spot on...the future will necessarily bring changes that must address that aggregated treatment survival benefit has extended life - and, having extended that life - how should we best manage that life extension? In a new-age hospice-driven treatment environment that has for past decades acknowledged OS as the "gold standard" - and in many ways achieved that standard - what new metrics of acceptability will provide a continued measure of therapeutic benefit for an aging group of survivors? In a prior post, you had suggested that the hospice community would have an increasing share of input wrt treatment approvals. How soon do you see this happening?

  • Reply to

    Cabo and Enzalutamide trial

    by wilderguide Aug 18, 2014 10:39 PM
    wilderguide wilderguide Aug 18, 2014 11:32 PM Flag

    $$$$
    Went looking a bit and found this...figured to post it as a heads-up. CCR June 2014, C Liu, et al...
    "Niclosamide inhibits androgen receptor variants expression and overcomes enzalutamide resistance in castration-resistant prostate cancer"
    Nicoosamide is a generic anti-parasitic - typically used to treat tapeworm. It has also shown pre-clinically to inhibit AR splice variants, such as AR-V7. Cabo may be a much more expensive choice to overcome resistance to enzalutamide. I'd still like to see if there is additional synergy. I wonder if this could be the reason for delay?

  • wilderguide by wilderguide Aug 18, 2014 10:39 PM Flag

    $$$$
    The following is an excerpt from the December 2,2013 PR that announced the initiation of the P2 combo trial with Abiraterone:
    “With its differentiated mechanism targeting MET, RET, and VEGFR2, we believe cabozantinib has the potential to be therapeutically complementary with prostate cancer therapies such as abiraterone and enzalutamide,” said Michael M. Morrissey, Ph.D., president and chief executive officer of Exelixis. “We believe that the results of this trial will provide important insight into the role that cabozantinib might play in earlier lines of therapy, including patients who have not yet received chemotherapy. This trial, and our planned phase 1 trial of cabozantinib in combination with enzalutamide, which is expected to start in the first half of 2014, should support our efforts to realize the full clinical and commercial potential of cabozantinib in CRPC.”
    I'd been looking forward to the initiation of the enzalutamide study, and am wondering what's up... ASCO 2014 had some good reporting on enzalutamide-induced resistance in CRPC, and assigned some heavy significance to AR-V7 as possible primary cause. The research also proposed similar mechanics of resistance for Abi... Last P1 trial reporting had at least one patient on dual Abi/Cabo therapy for over 20 months, and this would seem to infer that resistance to Abi was being mitigated by Cabo. The enzalutamide combo trial might prove to be a confirmation of AR-V7 involvement. I don't recall any mention at the ER. Any thoughts?

  • wilderguide by wilderguide Aug 18, 2014 6:23 PM Flag

    $$$$
    Ordinarily might not bother me, but he's given it to everyone today...
    Pridefully and forcefully...he has wielded that thumb like the mighty sword of Damocles...
    I hope this post stays under his radar, lest he toss that thumb at me.
    I don't want it. I know where it's been...

  • $$$$
    CA Philip, et al... Pubmed Central. From the abstract:
    "Targeted therapies such as pazopanib are now available for soft tissue sarcomas and so could be proposed for uterine sarcoma patients after first- or second-line chemotherapy in the metastatic phase. Further investigations are needed to determine their indications and targets. A European Organisation for Research and Treatment of Cancer (EORTC) randomized trial testing maintenance therapy with cabozantinib after first-line chemotherapy in HGUS is ongoing."
    PMID: 25123078

  • Reply to

    comet2

    by ieteriinto Aug 17, 2014 1:38 PM
    wilderguide wilderguide Aug 17, 2014 4:02 PM Flag

    $$$$
    If cabozantinib fails to display statsig OS in mCRPC, it can't justify it's hefty price tag.
    Pain relief is an FDA approvable endpoint, but the therapeutic value of that pain relief is - as yet - poorly understood. The mechanisms of Cabo's bone pain response are the target of many investigative trials that may eventually report a previously unwitnessed biological effect on the bone micro-environment. This could conceivably make Cabo a stand-alone bone-targeted therapeutic...perhaps justifying an enhanced valuation - but OS is key to commercial success in the prostate space.

  • Reply to

    Wow

    by csanderson1805 Aug 15, 2014 6:03 PM
    wilderguide wilderguide Aug 17, 2014 3:35 PM Flag

    $$$$
    "...they have the odds in their favor despite the fact that EXEL's science may very well be the real deal."
    It's got to be the real deal...
    Cuz it says so all over the internet.
    How could everyone but Milkman aka Nomad aka Jonesy be wrong? ; /

  • Reply to

    Wow

    by csanderson1805 Aug 15, 2014 6:03 PM
    wilderguide wilderguide Aug 17, 2014 12:47 PM Flag

    $$$$
    "I think big dollar contributors like to think their contributions are spent to good effect. PCF looks for winners and backs them. I think they are just echoing what they are being told by the alpha members of their Scientific Advisory Board, many of whom are participating in multiple cabo trials."
    This would explain the optimism, and justify the endorsement, but doesn't do much to help explain the ongoing (and growing) short play in EXEL. The growth of research into Cabo has mirrored the growth of research into the significance of the MET/VEGF axis in cancer therapy. Bif's suggestion that this might constitute a differentiating "buy" signal might soon be proven spot on, as I can see no such growth-oriented mega-interest amongst the competitors' METi products, nor is there another such controversial therapeutic in the near-term mix. Cabo has made a distinct impact on the research community, and translating that impact to one of significant commercial value doesn't seem that great a stretch of the imagination...so why the continued growth in short interest? Can all these motivated researchers really be wrong? Can all these dollars spent on Cabo research be wrong? Can all the time and energy be for naught? What is the rationale of the short thesis these days?

  • Reply to

    New patent application for treating Osteoporosis.

    by neers87 Aug 14, 2014 7:41 PM
    wilderguide wilderguide Aug 16, 2014 5:37 PM Flag

    $$$$
    If I recall correctly, the case for Cabo in osteoporosis was first brought to this MB by wildbiftek. The primary argument against was based on excessive toxicity (I think Ernie proposed this...). A patent application in this treatment area at least secures the IP, but it also makes me wonder what future trials we might see if a mere 5mg daily dosing has any beneficial impact on bone porosity...with perhaps no discernible toxic profile. Just a thought...

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