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Exelixis, Inc. Message Board

wilderguide 338 posts  |  Last Activity: 10 hours ago Member since: Jan 13, 2011
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  • Reply to

    Anti-tumor activity of Cabozantinib in HCC

    by wilderguide Apr 6, 2014 12:01 AM
    wilderguide wilderguide Apr 6, 2014 12:43 PM Flag

    $$$$
    "...will there be a presentation of this study at the AACR...??"
    If so, I haven't found it. If it has already presented in a different venue, I haven't found that either. Occasionally I get dead-ended in foreign postings that either won't translate...or translate too incoherently for use. Typically, the Chinese sites are the worst for this...
    If you recall, there had been lengthy board discussion on illicit Cabo use in China, as their take on international patent rights is at odds with the West. I keep looking, but I can't find much wrt this topic. It would lend great insight into future Cabo prospect if we could reliably count those numbers.

  • Reply to

    AACR 2014 4/5 - 4/9 San Diego

    by wilderguide Apr 5, 2014 5:51 PM
    wilderguide wilderguide Apr 6, 2014 12:31 PM Flag

    $$$$
    Fom "Targeting cMET and VEGFR2 in the Stromal Compartment..."
    " In agreement with our in vitro data, cabozantinib suppressed tumor growth in bone (determined by in vivo bioluminescence) and tumor-induced osteolysis (determined by X-ray). Tumor cells were isolated and in vitro cultured to demonstrate that cabozantinib resistance was maintained during 3-week in vivo growth. Osteoblasts and osteoclasts numbers were reduced in the bones of cabozantinib-treated mice, and these histological changes were accompanied by significantly lower levels of RANKL and M-CSF levels in bone. Collectively, inhibition of c-Met and VEGFR2 in osteoblasts reduces RANKL and M-CSF expression, associated with decreased osteoclastogenesis and tumor-induced osteolysis. Therefore, we conclude that c-Met and VEGFR2 are promising therapeutic targets in the stromal compartment of prostate cancer bone metastasis, suggesting hat the effects of cabozantinib on skeletal-related events of prostate cancer are, at least in part, mediated by suppression of osteoblast function."
    I'm not sure I've heard this take on Cabo MOA prior to this study. Denosumab is an approved RANK ligand inhibitor, and has been seeing prescription use in CRPC with bone metastasis...but it also has applications in osteoporosis. If these results hold up to the clinical microscope being held by the NIH funded studies currently in clinical trial, this might be construed as very good news. Hitting an unintended target in cancer therapy is not necessarily a unique experience, but it would seem this might be one further step in defining the Cabo bone phenom in terms of biologic benefit. SRE management, pain relief, narcotic reduction, and impact on visceral disease could make Cabo the drug of choice for targeting bone response, if this data translates to the clinic as we have seen in the past.
    GLTA

  • Reply to

    AACR 2014 4/5 - 4/9 San Diego

    by wilderguide Apr 5, 2014 5:51 PM
    wilderguide wilderguide Apr 6, 2014 10:26 AM Flag

    $$$$
    "I'm here and I'll take a look"
    Then you are a stronger man than I...
    I'd not get past a bucketful of fresh crab & a cooler full of beer on a warm stretch of sand.
    Have some fun!

  • Reply to

    Anti-tumor activity of Cabozantinib in HCC

    by wilderguide Apr 6, 2014 12:01 AM
    wilderguide wilderguide Apr 6, 2014 12:12 AM Flag

    $$$$
    Sorry,my bad. This Chinese study was published in the AACR journal Clinical Cancer Research.
    Forgot where I was...

  • $$$$
    Chinese study sponsored by the NNSF, Q Ziang, et al published in Nature 4/3/14
    "Conclusions: HCC patients with high level of p-MET are associated with resistance to adjuvant sorafenib treatment. The dual blockade of VEGFR2 and MET by cabozantinib has significant anti-tumor activities in HCC, and the activation of MET in HCC may be a promising efficacy-predicting biomarker."
    GLTA

  • Reply to

    AACR 2014 4/5 - 4/9 San Diego

    by wilderguide Apr 5, 2014 5:51 PM
    wilderguide wilderguide Apr 5, 2014 9:55 PM Flag

    $$$$
    Also found this Cobi presentation on Tues 4/8:
    Presentation Title: " Clinical results of a phase Ib dose-escalation study of the Mek inhibitor cobimetinib (GDC-0973) and the Akt inhibitor ipatasertib (GDC-0068) in patients (pts) with solid tumors"
    GLTA

  • $$$$
    $$$$
    Lots going on here, beginning tomorrow...
    I count 11 abstracts pertinent to Cabo...
    Amongst the ones I like best:
    4/7 Targeting cMET & VEGFR2 in the Stromal Compartment of Prostate Cancer Bone Mets
    4/6 - Evaluation of Cabozantinib in Combo with Abiraterone, Enzalutamide, or Docetaxel in a CRPC xenograft in Vivo
    4/6 - Effects of cabozantinib in Breast cancer metastasis, overall survival, and bone mass in a mouse model
    Lots of clinical and preclinical reporting this week...
    This oughta give ol' Jonesy Dingle-Berry lots to be thankful for...
    GLTA

  • $$$$
    Encouraging biomarker prognostics are being reported in the April 2014 BJC based upon statistics gathered in Japan and the UK. This survey is based upon monitoring of bilirubin, albumin, AFP-L3, AFP, and DCP with good international corroboration of application to date. This is a likely standard to which Cabo will be held in the global Celestial trial in HCC, particularly in approvals forthcoming outside the jurisdiction of the FDA.
    GLTA

  • Reply to

    Management of Thyroid Cancer

    by wilderguide Apr 4, 2014 5:40 PM
    wilderguide wilderguide Apr 4, 2014 5:53 PM Flag

    $$$$
    Behind medullary...that's 95% RET-driven familial...50% sporadic...
    Remember...European conditional approval contains the caution that Cabo clinical performance in MTC may be compromised based upon RET status. These are very compelling numbers, and this is very compelling news...JMO GLTA

  • $$$$
    New CME available FREE from Inpracticedotcom authored by Dr Corey Langer. Simple registration...
    Good chart on current breakdowns of driver mutation status by category of disease.
    Papillary- 20% RET....10% RAS....
    Follicular - 45% RAS...no RET reported...
    Medulary - Medullary 95. % familial....50% sporadic...(no mistake, 95%!!!!!)
    Good overall reporting with access to current NCCN guidelines. Worthwhile...
    Have a good weekend....
    GLTA

  • Reply to

    Comet -1 results

    by anitdua Apr 4, 2014 3:43 PM
    wilderguide wilderguide Apr 4, 2014 3:57 PM Flag

    $$$$
    Current guidance from IR is sometime in 2014 for both Comet trials.
    That info is per Susan Hubbard, and is current as of yesterday's e-mail per my query.
    Personally, I think we'll see a peer-reviewed presentation on each in Sept's ESMO...with initial reporting sometime in July...perhaps August, if OS results prove to be superior. Initial reporting will constitute only essential pass/fail endpoint info. Updated details will be at ESMO...Patience is a requirement here.
    GLTA

  • Reply to

    OT: another casualty of biotech.

    by metropath Apr 4, 2014 8:36 AM
    wilderguide wilderguide Apr 4, 2014 3:04 PM Flag

    $$$$
    I have traded HALO for a few years now, and really have been impressed with their development. I halved my position in the $14's...and glad I did. I'm looking to add down here, and recommend you consider an entry point based on potentials of SQ rituximab (MABthera) and HyQvia alone. I feel the halt to the Hylenex pancreatic study is a bit overblown, and the stock will easily recover into double digits by 3Q earnings reporting, if not sooner. This sort of news becomes disproportionate with a sector tumble, and I've added to EXEL below $3.50. I feel both EXEL and HALO will rebound much like ARIA.
    GL

  • Reply to

    Question for "Oncodoc"

    by stillwater9999 Apr 4, 2014 1:40 PM
    wilderguide wilderguide Apr 4, 2014 1:49 PM Flag

    $$$$
    Knowledgable as he may appear, do you actually expect that a practicing oncologist would have the time away from that practice for endless banter on a YMB? Regardless of pncodoc's reply to your query, I strongly reco that you do not solicit your DD in any such forum as this one, nor that you take anyone that posts chatter on a YMB too seriously - regardless of any appearance of credibility. Do your own DD, place your own bet. JMHO

  • wilderguide wilderguide Apr 3, 2014 7:12 PM Flag

    $$$$
    Hey Matt,
    There's a good posting at OncLive you'll want to be sure to find "Pre-Chemo Strategies in CRPC", posted today in fact. There is a lot of "wiggle room" in the treatment algorithm right now, and I think it most important to consider Cabo's entry into CRPC as a salvage therapeutic as the low-hanging fruit of currently availabilty spots in the sequence. Once approved, the many ancillary P2 trials will quickly find Cabo's placing in the therapeutic sequence, and perhaps even in combination in earlier lines of therapy. I don't really see that there is competition between Cabo and the hormone axis twisters, but rather the potential for complementary application - both in combo and in sequence. Different MOA's, different clinical profiles, differed responses in metastatic settings.

  • Reply to

    New Agents for Prostate Cancer (revised)

    by wilderguide Apr 3, 2014 12:15 AM
    wilderguide wilderguide Apr 3, 2014 12:32 PM Flag

    $$$$
    The Annals of Oncology is a pretty darned reputable journal, while the Clinicaltrialsdotgov site can only be considered to be as current as it's latest update. I'm going to say it's a pretty safe bet that Comet 2 was fully recruited somewhere between 3/5/14 ( last Clinicaltrialsdotgov update)...and 3/20/14, when the final revision of the Agarwal "New Agents" article was posted.

  • Reply to

    New Agents for Prostate Cancer (revised)

    by wilderguide Apr 3, 2014 12:15 AM
    wilderguide wilderguide Apr 3, 2014 11:30 AM Flag

    $$$$
    Yahoo no longer permits link postings. If it helps, the Annals of Oncology site is a function of the Oxford Journal. How in the world did you ever find the YMB?

  • Reply to

    New Agents for Prostate Cancer (revised)

    by wilderguide Apr 3, 2014 12:15 AM
    wilderguide wilderguide Apr 3, 2014 11:22 AM Flag

    $$$$
    In looking at additional revisions to the original publication, I see that TAK-700 is appropriately updated as to OS failing it's endpoint. This update was not in the original printing, and didn't report until late Feb (I think) For purposes of investment, I'm going to consider it wise (failing additional info) to assign a data lock date of June 19 at the latest - and most likely earlier - for Comet 2 final results. With this in mind, I think it important to consider that Comets 1 & 2 could report in the same timeframe. Perhaps the same week...
    Unlikely as it sounds, imagine getting positive data return from both Comets in the same PR - wouldn't that be a hoot?
    GLTA

  • $$$$
    I know...I know...this has been posted before...N Agarwal, et al..Annals of Oncology 3/20/14
    But here's the scoop I'm seeing, and figured I'd toss it out there for commentary and possible corroboration. The peer-reviewed and finally accepted copy of this document is dated 3/20/14... less than 2 weeks ago. Look at page 4 of 9 in the "trials in progress listing" . Comet 1 & Comet 2 are listed separately and distinguished by NCT trial numbers and different endpoints. Both are listed here as "accrual complete" and "results pending"...
    Typo or good news unintentionally delivered? I suppose it could be a typo...But - would someone else please take a look, make sure I am seeing this correctly. It would be just like these EXEL mgmt jokers to blindside us with news out of the blue...But, if Comet 2 has already accrued, there is a clock ticking that might mean payoff.
    GLTA

  • wilderguide by wilderguide Apr 2, 2014 9:10 PM Flag

    $$$$
    New IST sponsored by the University of Alabama...P2, low enrollment.
    Interesting disease with a lot of clinical manifestations. The interesting take on this trial is that there are a few return clinicians from the Cabo pediatric trial in solid tumors. I like to see return onco-docs..it's the best assurance you have that they have returned to access a clinical tool in which they have found value.
    GLTA

  • wilderguide wilderguide Apr 2, 2014 4:22 PM Flag

    $$$$
    "However, as with other therapeutic agents, resistance to cabozantinib rapidly occurs in both our model system as well as humans...(would that mean) that Cabo would be left out in the cold?"
    Good point, Clem... And I have to admit, I had reservations in posting that MDACC trial info...and for the very point you mention. Interpreting durability results in the absence of actual trial reporting is difficult. EXEL has really only given outlier info wrt durability of response, and the difficulties of making inferences has made this a risky bet. That said, treatment-induced resistance is not specific to Cabo, and is a problematic orientation in many cancer therapeutics. As popular as VEGF treatment has become, it's durability is limited...and Cabo seems to work in VEGF-resistant populations. I'm trying to keep unreported DOR in context, yet keep an eye on it. Undeniably, durability of response and overall survival are proportionately linked...Wish I could offer you more reassurance, but there it is.

EXEL
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