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Exelixis, Inc. Message Board

wilderguide 396 posts  |  Last Activity: 3 hours ago Member since: Jan 13, 2011
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  • Reply to

    Cabozantinib in LADC/ NSCLC

    by wilderguide 10 hours ago
    wilderguide wilderguide 3 hours ago Flag

    $$$$
    Truth is we can't tell, not knowing her particular variety of mutational driver, but erlotinib does not fit the description of "new"... Far from it. In addition, the lawsuits are already beginning to fly over generic manufacture of Tarceva. It is far from "new".

  • Reply to

    Cabozantinib in LADC/ NSCLC

    by wilderguide 10 hours ago
    wilderguide wilderguide 8 hours ago Flag

    $$$$
    "Yeah, she'll croak and no one will care."
    This is the most socially irresponsible and ignorant statement I have ever heard.
    You are an idiot...

  • $$$$
    Just a hunch, but based in part on the lack of substantive media coverage. International lawmaker and Sen Miriam Santiago has just announced that she has been diagnosed with stage 4 lung cancer, and the media is saying very little about her treatment other than it is a new "chemotherapeutic" pill. I figure the suspense will subside over the next few weeks, and I won't have to guess any longer...

  • $$$$
    Journal of Nuclear Med 2014 Supp 1; 402...Katherine Zukotynsky, et al
    "Prognostic value of baseline evaluation of FDG and NaF PET/CT in castrate-resistant prostate cancer (CRPC): Early results from a prospective phase 1 trial"
    I don't think this study got tossed out for discussion, but I think it's important to consider future direction as it becomes available. Here, these early study results seem to indicate that - in the future - CRPC treatment groups may be stratified into three subset groups, apparently based upon metastatic staging and FDG sensitivity. Determining which of these patients are most receptive to the combination of Cabo and Abi will undoubtedly help determine the best targeting of a future P3 trial.
    GLTA

  • wilderguide wilderguide 13 hours ago Flag

    $$$$
    In the face of ongoing expert commentary - both in publication and practice -I am increasingly confident that Cabo will find it's way into the treatment algorithm in CRPC. However, actually defining that entry point is still troublesome, though androgen resistant, heavily treated pops currently appear to hold the lowest bar for a gainful foothold. I also continue to believe that the rationale for combined AR/Cabo therapy is sound, and I anxiously await future low-dose Cabo study results with both Abi and Enzalutamide.
    Cabo really needs a predictive biomarker to enable therapeutic guidance. The literature is replete with the importance of cMET inhibition in treatment-resistant cancer therapy, but the predictive mechanisms to ensure patient response have proven elusive. Should Comet-1 fail to achieve it's endpoint of statsig OS, I remain convinced that a subsequently designed biomarker-guided trial will display Cabo efficacy with a survival benefit to boot.
    Just a matter of time and patience...

  • $$$$
    Dr Kurt Miller, Chief Urologist Ben Franklin Medical Center, Berlin Germany
    Available at ecancerdotorg. Published 5/12/14. I think this lecture actually took place at the Asia-Pacific Prostate Cancer Conference last March. Good presentation. Dr Miller has published and co-authored extensively on Cabozantinib. My suspicion is that he expects approval. JMO

  • Reply to

    Drip Drip Drip

    by dex11ter Jul 10, 2014 8:25 AM
    wilderguide wilderguide Jul 10, 2014 8:46 AM Flag

    $$$$
    Hi. My name is Darrell.
    I'd like you to meet my brother, Daryl.
    ...and this is my other brother, Darrill.

  • Reply to

    anyone follow snta

    by mj525252 Jul 9, 2014 10:47 AM
    wilderguide wilderguide Jul 9, 2014 12:18 PM Flag

    $$$$
    I have a position in SNTA. They have some interesting IP in their HSP90 drug conjugate program, and though it is very early in development, the workups to date look promising. They have patented hundreds of HDC compound combinations, and I view an HDC partnering process as inevitable. In addition, their lead oncodrug candidate, ganetespib, has shown some interesting results...including a couple of CRs in TNBC. Bruce Kovner and Caxton investments hold a very high percentage position in SNTA, and I have tried to buy when they do. The HDC program - if successful - would strongly differentiate SNTA from all existing biotechs. HSP90 inhibition will likely find some treatment space in oncology, and ganetespib has a comparatively reasonable AE profile. JMO

  • $$$$
    Good slideshow w/ current info on melanoma treatment: checkpoint inhibitors, immunotherapeutics, targeted therapies...all in one presentation. Well produced from Clinicalcareoptionsdotcom. Free. You simply need to sign up. Brim7 gets good coverage, and all the competition stats are close at hand. Jeffrey Weber, MD of Moffitt Cancer Center presents...
    GLTA

  • wilderguide wilderguide Jul 8, 2014 8:58 AM Flag

    $$$$
    Sounds to me as if the only cure for you is a 10-lb cabozantinib suppository.
    Guaranteed to quit all those voices in your head...

  • wilderguide wilderguide Jul 8, 2014 8:51 AM Flag

    $$$$
    Thanks for keeping me honest, Hbomb.
    So many cellular interactions, so little time.

  • Reply to

    Pump.....and then Dump!

    by offsitehelp Jul 3, 2014 11:15 AM
    wilderguide wilderguide Jul 8, 2014 8:34 AM Flag

    $$$$
    Why is it that you and your aliases are the only dipshizzles on the planet that refer to cabozantinib as worthless IP...?? There are over 50 clinical trials of this compound in progress, over two thirds of which are sponsored by OPM. Doesn't that even begin to suggest to you all - all of you - that the clinical interest in Cabo is running on high?
    How many aliases will you post as today?
    I absolutely enjoy it when you respond to yourself...
    ...once you've realized that no one else will...
    A most fascinating character y'all must be...
    Y'all hear voices too?

  • $$$$
    Cancer Discovery, July 2014 Yi Feng, et al
    Some interesting discussion implicating a novel cMET signaling pathway with tumor escape and treatment resistance in breast cancer. This is the first reference I have seen tying SPSB1 to cMET activation. This work-up makes me consider the therapeutic rationale of the MGH-sponsored Higgins/ Tolaney trials of Cabo in mBC. - both as a monotherapy, and in combination with the anti estrogen, fulvestrant.
    An excerpt from the introduction:
    "The principal cause of death from breast cancer is recurrence. This study identifies SPSB1 as a critical mediator of breast cancer recurrence, suggests activation of the SPSB1–c-MET pathway as an important mechanism of therapeutic resistance in breast cancers, and emphasizes that pharmacologic targets for recurrence may be unique to this stage of tumor progression."
    GLTA

  • Reply to

    Pump.....and then Dump!

    by offsitehelp Jul 3, 2014 11:15 AM
    wilderguide wilderguide Jul 8, 2014 2:04 AM Flag

    $$$$
    No one invested in developmental biotech has any real hope for short term earnings,
    Go back to pudd-pulling with your multiple aliases...it's all you really know.
    You wouldn't make a decent zit on a real TA tech's tooshie, dooshwaddle...

  • wilderguide wilderguide Jul 8, 2014 12:54 AM Flag

    $$$$
    These are the beginnings of some great discussion, but a lot of the literature is still very new to me. My current understanding is that MAPK upregulation is present in some 50% of BRAF-mutant melanomas, and seems to be durably mitigated by concurrent BRAFi/MEKi. This synergistically beneficial combination has only recently been recognized in the clinic, though the rationale has been bantered about for a few years. By way of contrast, METi is (relatively speaking), the new kid on the block. I don't think the impact of cabozantinib treatment has been defined as yet in terms of MAPK activation, at least I don't recall seeing it the lit...
    But, there are studies are in place to closely examine exactly what biological play is responsible for treatment-induced resistance to Cabo. Doc Logothetis is spending SPORE money at MDACC to validate the concept of "osteocrines" - bone-secreted enzymes that may be responsible for systemic resistance to cabozantinib. These recent findings tying MEKi to sustaining MET inhibition open new doors of perception wrt the overall importance of concurrently modulating MAPK, and may even lead to considerations of a generalized MAPK prophylaxis as marker-driven METi therapeutic strategies are developed.
    A successful outcome in Comet-1 threatens to shoot some big holes in existing conventional wisdom. Confirming BSR as a predictive marker for OS is the most obvious, but consider that the whole enchilada is at play here. Positive bone turnover markers, CTC redux, improved LDH elevations, improved serum hemoglobin content, pain response, durable narcotic reduction, and the entire precept of Cabo-induced hrQOL (improved motility, restfulness) considerations are up for validation as associative of improved survival. Cabo stands to be a real game changer - and especially so - if durability of response can be improved upon. MEKi might be one step in that direction. GL

  • Reply to

    ASCO 2014 - Takeaways for PCa Cancer Patients

    by wilderguide Jul 1, 2014 9:27 PM
    wilderguide wilderguide Jul 7, 2014 6:57 PM Flag

    $$$$
    The Emma Shtivelman article is lengthy...too lengthy to put up in its entirety. The excerpt I posted is really all she mentions of the Cabo/Abi combo. Take a look at Clinicaltrialsdotgov gov for info on the two combo trials - NCT01995058 & NCT101574937. Glad to have you aboard, doc...

  • $$$$
    Whatever became of those insidious, sure-fire precursors of technical doom?
    Only offsite's proctologist knows for sure. The procedure was short, sweet, and successful.
    Looks like this message board has had an analectomy.
    Ain't that right, drizzlebritches?

  • Reply to

    Question

    by who_gnu_1235 Jul 6, 2014 11:26 AM
    wilderguide wilderguide Jul 6, 2014 11:52 AM Flag

    $$$$
    "Stock tanked when interim P3 analysis recommended that P3 proceed to completion. Why is this bad?"
    The easy answer is that the Street's disappointment was relative to the early trial successes of Abiraterone, Enzalutamide, and Alpharadin. Folks that have followed the clinical evolution of cabozantinib know that the drug will not compete with the AR modulators...nor with any radio pharmaceutical. It has it's own distinct clinical signature, and may very well complement other CRPC treatment strategies, particularly in advanced metastatic disease where bone lesion pain and morbidity are of concern.

  • $$$$
    "In this inPractice® module, Brian I. Rini, MD, reviews the latest research on the causes, diagnosis, and new treatment approaches for RCC to help you make optimal decisions for your patients"
    Well-organized rundown on current SOC and CW. Cabo, Nivolumab, and dovitinib get covered at the very end of the training syllabus as the potential new-comers. Good CME, and it's a freebie from iInpractice Oncology.

  • $$$$
    "Were those black candles or sticks of dynamite?"
    Sounds like a good title for Chapter 11 of your autobiography...
    More top marks for your TA, drizzlebritches...

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