"I miss seman..."
I think I can say with confidence that - if you shop around over the holiday with the persistence you have displayed on this MB, you will have no problem at all in finding a seman donor. In fact, near as I can tell...
He's warm for your form as well...you guys have some fun keeping the joint warm, OK?
"M&A: Buckle your seat belts for another big round of deals"
December 24, 2015 | By John Carroll
Good luck to all & Happy New Year!
...OncoDoc Ghassan Abou-Alfa. Lots of good info here on status of HCC research. He touches briefly on the advantages of a multi-kinase approach to HCC treatment, has a few words on Cabo, lenvatinib, tivantinib, and durvalumab HCC trials in progress.
"The Use of Genetic Alterations in the Development of Liver Cancer Drugs"
Gastroenterology & Hepatology
December 2015, Volume 11, Issue 12
I found this while looking for some insight into CELESTIAL recruitment. The lenvatinib vs sorafenib frontline comparison trial initiated in March 2013 & just reached full enrollment in Sept 2015. Considering the number of trials in progress and also that CELESTIAL is placebo-challenged, recruitment may indeed be quite slow. JMO
Oncology treatment approvals are most often made upon the clinical premise of survival benefit. You'll find that most frontline therapeutics are so assigned because they have displayed enhanced survival. Cancer biology is an evolving science, and large cautions are advised in entering new treatments into the algorithm - particularly those with known toxic profile. Many treatments actually alter the biology of the disease, and post-treatment regimens may prove ineffective in the wake of a failed treatment approach. Surrogate approval trial endpoints have evolved over the past decade to enable shorter, less costly trials - as waiting for survival benefit to present can take time to elucidate effectively. Hope this helps...
Take a look at the Market Exclusive article by Jennifer Aldershot - "The Science Behind Exelixis' Billion Dollar NDA". While somewhat naive in its presentation (Cabo is much, much more than a "dual inhibitor), the article carries the weight of acknowledgement that the science is in a mode of increasing adoption. EXEL's drug discovery platform is slowly but surely finding its way into the oncology clinic, and there are undeniable milestones of progress. Cabozantinib has been the target of huge research interest for going on 4 years, and the pool of data reaching maturity will soon reflect the value of that research. This is not a good place to be short for 2016...
"Preclinical Evidence That Trametinib Enhances the Response to Antiangiogenic Tyrosine Kinase Inhibitors in Renal Cell Carcinoma" published in MCT 12/28/15...Victoria, et al...
This workup explores the combinations of both sunitinib and pazopanib with the MEKi Trametinib. Cobimetinib gets mentioned as a likely candidate for combination citing its success in melanoma with Vemurafenib. This is a fortuitous finding that may provide new direction for Cabo should the NCI/ Apolo trials with nivolumab go Tango Uniform and end up in the round file.
This rationale makes an even stronger case for a Roche buyout.
Ernie posted the excerpt below some time back regarding the capsule vs tablet... It prompted me to seek some FDA guidance on the topic, which I'll try to post below:
"This is actually a bit of a complex situation and let me fill in the background for the readers. First the tablet vs capsule thing. Cabo for MTC was approved as a capsule. Cabo for RCC is a tablet. It meant that EXEL could not take the regulatory shortcut and submit a supplemental NDA for RCC. They decided to start from scratch and do a full submission. The advantage is that it separates the indications and EXEL can charge whatever the market will tolerate for each separately. Practically, I sincerely doubt there is any appreciable difference between the two from a patient's perspective, but from a regulatory point of view, they are different medicines."
Cometriq dosing methods - whether dispensed in capsules or tablets- are not necessarily considered bio equivalents...at least not from a regulatory standpoint. I'm not sure how much this alone can slow the approval process, but the fact is that approving the tablet will take longer than if EXEL had opted for a label expansion (sNDA). Information on bioavailability, absorption rates, and half-life concentrations will necessarily be hashed thru and digested in the process.
Farts Are Tasty...
It's a Wall Street protocol practiced by Young Republicans, Erstwhile Democrats, and all EXEL shorts...
...and to all a very, very Happy...
"But the answer is in the FAT."
Final Acceptance Test?
Foul After Taste?
Faithful Amd True?
Forest And Trees?
2 credits gosh darn it!!!!
That oughta be worth more than a paltry 4 thumbs down!!!!
C'mon Shorty, show me yer stuff...
As a CME valued at 2 AMA PRA Category 1 Credits, I'm betting this is a very popular event.i think these PERS programs are videotaped to optimize clinician exposure, and I'd also bet we'll see this one online in the near future - Practice Update, OncLive, etc. Four well-published KOLs addressing the utility, sequencing, and proper dose management of your RCC treatment is pretty cheap advertising, as well. I'd enjoy attending this one myself...
Interesting educational symposium peripheral to ASCO GU...
"Renal Cell Carcinoma: Recent Advances and New Questions"
Date and Time: Thursday, January 7, 2016, 6:45 PM
Oncodocs Rini, Hammers, Choueiri, and Figlin discuss the evolving algorithm
Made possible by an educational grant from Exelixis
"They (CHMP) already approved an accelerated assessment...."
A condition of review that can be withdrawn at any time deemed inappropriate to the evolution of the treatment algorithm. Best case scenario I see for Lenvima in RCC is a conditional marketing approval based upon unmet need within the approved treatment space, and next months' ASCO GU should lend further clarity. Lots of data delivery on TKIs in the space, and lots more in checkpoint Immunotherapeutics as well. At the risk of seeming overly optimistic - I think METEOR reporting was very fortuitous in its timeliness, very well received academically, and bodes well for clinical adoption. The recently updated EAU & NCCN RCC guidelines bear this out, and I see difficulties in adding to the existing treatment algorithm till the existing treatments get sorted out - particularly if the evidence presented is of low statistical representation. I actually favor Lenvatenib, I just don't see that Eisai has made their case in RCC with 100 patients...
Given the small data pool available for lenvatinib in RCC, I think the cards are stacked against Eisai until they can produce a larger trial. Too few data, too small a patient group (to my knowledge, approx 100 pts treated with Lenvatinib or combo to date), too high an AE index, and too many AE5s attributable to Lenvima (I think 2 out of 100+ treated). They have already been unanimously declined consideration by NCCN a for compendium listing due to too-low level of evidence.
JMO, but I feel that lenvatinib will be perceived in RCC as Cabo is perceived in DTC - promising, but late to the game.
So many thumbs down to such an innocently presented opinion - it's like they let the fabulous furry freak brothers out at the funny farm. I feel betrayed. It's like I spent all afternoon making great hashish brownies with crushed almonds and colorful sprinklies just to find that you selfish farqharts ate 'em all while I was out back practicing fly fishing presentations in my padded fatboy Santa suit with the fuzzy codpiece.
It doesn't do to betray St Nick...
"..I was totally under the impression that I was...
...on a different board..."
It must get somewhat confusing at times...
Different aliases...differed agendas...different MBs...
No concerns for identity theft...
It ain't worth taking...
Who'd want it?
..."I realize AF is just a fictional character, nothing more..."
Are you suggesting that perhaps AF is to Cramer...
As Seymour is to Aisan...?