Just to provoke some further thought in this area, check this out:
"Progression Free Survival: Meaningful or Simply Measurable?"
JCO 4/2012... Booth & Eisenhauer
This work-up raises lots of questions wrt PFS, OS, QOL considerations, and defining therapeutic benefit in relation to a clinically meaningful balance of these benefits. I've returned to this document many times to consult/confirm my perceptions of Cabo...
My take is simply that effective therapeutic decisions in the post-progression treatment arena are destined for redefinition, and there will areas within the treatment algorithm in which OS importance will be reconsidered to favor intervention most appropriate to personal genomics, status of disease progression, and unmet need. Obviously, this can only play with some regulatory change, but I expect to see the most significant re-posturing to come from within the NCCN as best levels of evidence are generated.
"...in the near term, how about just putting patients in salvation therapy on Cabo for an initial 6 week interval. If bone scans improve, CTC levels decline, and pain palliation occurs...continue therapy...the data suggests you will live longer and with a better QOL."
We're on the same page...
The reality we are faced with is that drug approvals of the future are not likely to be as "black & white" as past FDA guidance has dictated. I expect unmet needs to become increasingly apparent as existing approved drugs are incorporated into the algorithm, and I begin to suspect there will be recognition of stages of CRPC where indicated PFS controls may temporarily overrule longer-term OS concerns. Segregating the importance of PFS vs OS might be as simple as recognizing the need for timely and most appropriate intervention, but regulatory change seldom keeps pace with recognized clinical need, so I expect continued controversy - even in the wake of superior Comet-2 results.
"Does that necessarily mean that if Cabo was used as the FIRST line of defense (much earlier in the diseases progression), that Cabo would be as ineffective?"
Not at all. The trial results are still being analyzed, and all we have really been told is this:
The cabozantinib treated patients performed inline with trial assumptions. Expectations based upon the OS analysis of the P2 RDT expansion cohort were met, and the resultant mOS of 11 months has pretty much confirmed the 10.8 mOS reported at ASCO 2013 by Doc Scher. Unfortunately, the prednisone control arm performed much better than anticipated. The reason for this is currently unknown. Dawginlife's commentary wrt dropout rate being a critical ingredient is spot on, as I suspect that we'll find that some patients from the prednisone arm left Comet-1 - their OS signal confounded by subsequent interventions. This is all inference, and the devil will remain till the final analysis. WRT your question regarding Cabo use in earlier lines of therapy - this question cannot be answered based on what has been revealed to date from Comet-1. I'm hopeful to see Comet-1 presented at EMUC 2014 in Lisbon, Portugal this November - but again - we'll need to see what unfolds.
"What difference will some specific data mean now?"
This is the phrase that has sold me. I'm no longer betting on the data, I'm gonna go with the real gold...
I'm gonna bet on everything Offsitehelp spouts...
Yeah, that's the ticket...
"Second is that the compound is ineffectual..."
In the face of a trove of existing, peer-reviewed data...this is an abject lie.
Quick...somebody call the ToS police...
PFS was statsig in the Cabo group compared to the Prednisone group. MMM discussed this in the conference call, and again at the MSGHP. PFS was an investigator-initiated endpoint not considered to be predictive of OS in CRPC.
In OS, Cabo performed pretty much as anticipated. The prednisone arm performed better than predicted.
" I am probably quite a bit older than..."
Right You be sure to let us know when your IQ catches up to your age...
Somebody hand Ol' Quasimoto here a bedsheet so he can wipe himself...
Duckduffer, I've been looking for an opportunity to pass along an interesting piece of DD, and this is it:
Check out "The Changing Landscape in the Treatment of mCRPC" published in the journal Therapeutic Advances in Medical Oncology 2013 by El-Amm & Aragon-Ching. This treatise hypothesizes rationale for treatment sequencing relative to clinically recognizable stages of symptomatic/asymptomatic and aggressive vs dormant disease. Progressive hallmark staging and re-staging considerations may be futuristically best defined by improved understanding of the natural history of the disease, and sequenced interventions may be said to "plug & play" to best accommodate each shifting tide. The profiling the authors have leant to symptomatic disease with bony involvement does everything but stand up and shout "Cabo"... Solid read...
Watch out, the Yahoo ToS police are watching you...
Cyber-castration is not beyond their capability.
Mountain oysters, anyone...??
Thanks for putting this info on the board, Clem...
Datasphere type systems will become commonplace for cancer prognosis , and the IBM Watson holds a promising position in the coming techno-wave. The overall imperative of computer-driven prognostics will become most pronounced as the biomarker-guided treatment sciences mature to viability. Oncologists are already driven to the edge of performance by the glut of new data, and software-managed supplements to CME structure will prove an invaluable research tool. In addition, subscription fees may prove modest enough to enable patients, patient advocates - and perhaps even investors some form of reasonable, affordable access.
"Their best and only shot to do anything is a dud"
Better hang on tight, I think yer about to get one of those "instantaneous" visits from the Yahoo ToS police.
Keep spreading that horse manure, cowboy...
"If I were to spread lies, I would instantly get a warning from Yahoo that my account would be suspended for violation of the ToS. If I did it again, that would be it." You mean it never would occur to you to use another alias...???
Way to schmooze, Barely Manilow...
When you headed in for that gender reassignment?
In addition, I also take MMM's refusal to make any comment on Comet-2 recruitment numbers as a positive. If a decision had been made early on to recruit Comet-2 till Comet-1 read out - regardless of the actual patient numbers - it could only enhance the trial dynamics. Should this prove to be the case, there will be an additional OS (secondary endpoint) read out downstream that may prove viable. Exploring the regulatory pathway going forward in CRPC will not be an easy task without statsig OS data, but it's certainly not inconceivable.
The Comet-2 trial updated to "active, not recruiting" status on 9/4/14 with 82 trial centers participating. Although it's not likely that all centers have recruited to maximum, simple math indicates that only 3 patients per center would achieve planned enrollment of 246. The situation may not be quite so dire...JMO, but I suspect they've managed to recruit over 200 patients, and the statistical review can be mathematically compensated to accommodate new numbers. This is really no big deal, providing those numbers are still acceptable to the FDA regulatory review process. With the approval of so many new and effective therapeutics in recent years, CRPC will prove a difficult indication to recruit for many next generation drugs, and Cabo will not be the only victim of this "failure to enroll" phenomenon. At the very least, we can presume that data lock will take place no later than 12 weeks beyond 9/4/14, so it's reasonable to assume top line results by the first of the year as company guidance has suggested.
4) Short hedge fund cubicle lackey
5) ". ". ". ". ". : Employed by Roche to provide pre-take out control of market cap
6) Barry Manilow impersonator working to keep himself in sequins and fishnet attire
"Everyone is waiting to hear your opinion."
We'll wait no longer, here it is...
You are a knee-jerk nitwit. When the dust clears you'll be proven for the fool you are. Cabo will find placement in CRPC based upon a modest survival benefit, pain relief, improved patient function, and various improvements in biomarker analysis, bone metastasis free survival, and overall improvement in hrQOL in a population of late-stage mCRPC patients that are beyond the response capability of all other existing therapeutics. It's called unmet need. Grow a set, dummy...
Is that opinionated enough for you?
"...blah, blah, blah Chapter 11 filing...."
Thanks once again for your insightful contributions based upon nothing other than conjecture and innuendo. Worthless drivel, just like your life...
Print this page out and wipe yer pooper, you useless tool...
Pretty astute observation, truffles.
If the final data sort-out permits, I expect we could see a future Comet-1 presentation with some interpretive release pertinent to the potential for confounded OS data as a result of the dropout rate, subsequent interventions, and stack-on therapeutics, etc. EMUC at Lisbon is a Nov possibility...
I was actually thinking more along the lines of:
"Offsitehelp mans up, puts on his big boy pants, and grows a set of cajones"
Now there's a meaningful headline...