Clem, here's a little open access read for you - posted in the European Journal of Cancer 3/15/15. The study is relative to hrQOL benefit derived from Dabrafenib plus Trametinib combination therapy vs Dabrafenib monotherapy in advanced mM. This was a P3 study. The conclusion:
"This analysis demonstrates that the combination of dabrafenib and trametinib provides better preservation of HRQoL and pain improvements versus dabrafenib monotherapy while also delaying progression. (Clinicaltrials.gov registration number: NCT01584648)"
JMO - but I suspect similar results are possible from such a trial with V&C, though Roche may not pursuit such a study unless it becomes a competitive marketing requirement. The rationale is in place, and they may just run with it.
"If you're not seeing efficacy now, you're not going to see it later."
Did yer Mama have any children that received an education?
"...I wonder if Roche is doing anything with Cobimetinib as regards Lung Cancer?"
I like this question, and have some opinion to share. I've thought about this a lot, and though the evidence is only beginning to emerge, there are a couple of pointed issues with Vemurafenib prescription that may turn cobimetinib into a likely pair-up in any indication for which Vemurafenib may prove effective. 1) BRAF inhibitor V has shown to upregulate MAPK (known as paradoxical MAPK activation), which may be - in part - responsible for treatment-induced resistance to BRAF therapy. Cobi apparently resolves this, at least as shown in advanced mM in the CoBRIM setting. 2) Also in melanoma, the combination of V&C has shown to be less effective if prescribed in the wake of BRAF monotherapy. IOW - greater PFS,
ORR, TTP, and response durability has been recorded if the combination is prescribed as a couplet from the beginning of therapy vs V alone followed by the combination therapy. If either of these two conditions - or both - spill over into other indications, it's pretty clear that the combination might be prescribed ONLY as a doublet in the best interest of the patient.
"If she wasn't speaking publicly because of lawsuits...
...she wouldn't have commented at all..."
Another fake oncodoc off to iggystanisland...
Give it up, dooshwaddle...
If yer a doc...yer a doctor of dooshwad-ology...
This discussion is beyond pathetic. Jesi's legal counsel has obviously written her script, and anyone in her shoes would follow legal advice. Her particular situation warrants non-disclosure pending litigation. No one speaks publicly with lawsuits pending. No one. Get over it...
Seymour said it all in one of his last posts...
"Sometimes you trade, and sometimes you get traded..."
He conveniently forgot to mention that sometimes he just trades cubicle jockey IDs...
"You are quite incorrect."
You are right, I am absolutely mistaken. Evidence-based medicine has no place in oncology, and the NCCN compendium is a wishful fairy tale device that investors keep praying someday becomes a reality.
"I guess for the field of signal transduction inhibitors the next frontier is stacking and multi inhibitors..." I agree, with the addition of maybe planned TKI "switching" therapy...which seems to disarm (for a time) the onset of treatment induced resistance. At times, chasing mechanisms of tumor escape seems a bit like hunting prey that possesses the invisibility of a cloaking device - making for difficult treatment decisions in downstream therapy. As Cabo has displayed efficacy in so very many refractory and heavily pretreated patient groups, I've always felt it might always realize demand in salvage situations where approved SOC treatment options have exhausted.
"Cometriq off label!...increased revenue?""Analysts have high regard for increased revenue..."
Salvage use will always be a hit-or-miss proposition. Unless it coincidentally finds support in an NCCN compendium listing, insurers will forever be reluctant, and special applications will slow the prescription process. Analysts' regard for increasing revenues - in my experience - is limited to consistently, reliably, predictably increasing revenues. You simply cannot predict revenues based on off label use in an evolving treatment landscape.
Re: largest purchase:
Abstract PO-1-8: good case study of successful TKI-switching strategy using Cabo as 2nd line therapy post-Sutent. Notably, I can only find this strategy of Sunitinib to Cabo to Axitinib in the European literature.
Visit the website - patientsvilledotcom. Do a site search for Cometriq:
Unfortunately - as this site is set up specifically for AE reporting - there is no spin available wrt efficacy. However, there's some good info here regarding off label prescription and dosing with examples in STS, HCC, RCC, CRPC, glioblastoma, NETs, and CRC. Co administration evidence with bevacizumab, cetuximab, and many other chemo therapeutics suggest a fair degree of late stage and salvage use in unmet need. Cabo appears to be seeing its share of off label use.
I'm not sure what to expect here. If we don't see an E1512 update at ELCC, we may not get one till ASCO. Erlotinib has gotten its share of ESMO coverage, and makes me consider the politics of disclosure - patent expirations, etc. Further review of the E1512 trial reveals bi-weekly (and sometimes daily revisions) since the beginning of the year. Someone is spending a lot of time updating. This is a bit beyond my scope of experience - not sure what to make of all the "Dotting of I's; Crossing of T's" - but feel big news in the making. Given the context of trial maturity, and last interim reporting, JMO, but I feel it can't be bad news. We'll soon see...
"They lowered the dose to 60mg. Why?"
I suspect that the P2 dose-ranging study conducted by Matt Brown of Mass General was used to inform the dosing of Meteor. In addition, there has been ongoing evidence across the spectrum of indications that dose reduction was nearly always a mandate when initiated over 100mg BID. Off-label prescription (as shown in the Kidney Cancer Chronicles) is another likely source of dosing instruction for mRCC. At any rate, the Cabo balancing act of efficacy vs tolerance has been problematic. You are spot on in questioning Meteor dosing, as - to my knowledge - there is no large scale, clinically objective trial data to insure success in that indication. It's a bit of a wild card...
Here's what we know, based on the info divulged in the 11/4/14 press release:
"In the E1512 trial, 125 patients were randomized to one of the three arms: erlotinib, cabozantinib, or the combination. During a pre-planned interim ECOG-ACRIN Data Safety Monitoring Committee analysis for futility, it was found that the trial met its primary endpoint of improving progression-free survival (PFS) with cabozantinib alone and also with the combination of cabozantinib plus erlotinib, as compared to erlotinib alone, and the results were highly statistically significant. Safety data were consistent with those observed in other trials of cabozantinib. At time of analysis, the median follow-up was 5.9 months and overall survival data were immature.
The results of the trial are the subject of ongoing analyses and will be submitted by the investigators for presentation at a future medical conference."
This study - sponsored by the NCI, and chaired by Doc Joel Neal of Stanford - is the P2 Cabo NSCLC trial that reported positive top-line results on 11/4/14. In that EXEL PR, presentation at future venue was suggested. A quick review of revised updates to this study reveals that the study has been updated nearly each day of this month. Color me optimistic, but if we don't get news regarding this study during tomorrow's market, I think we are in for show-stopping news come Saturday. Oughta make for an interesting Monday...hope y'all have taken advantage of this pullback.
FYI - the ELCC 2015 news site updates regularly during the conference. It's an easy Google...GL
"They should hire you to run their PR..."
I think you hit the nail on the head - twonk is EDAP PR, IR, and probly CEO...
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