Good point that makes me wonder - in view of all the Cabo CRPC P2 studies in place - what sort of info might eventually be included in an SNDA pain filing in that indication. Aren't they also as likely to add tumor shrinkage, bone resorption markers reduction, etc. A pain approval based upon a non-narcotic, non-analgesic, unknown MOA might want to carry with it some clinically viable explanation of how that pain relief is achieved.
If you haven't found this yet, check it out...
A stages-show musical comedy act named Gene Burnett wrote this in response to the last recession.
There are a couple of versions available on YouTube....they all have enterprise.
Have a good weekend!
Possibly worth a mention is the secondary OS endpoint in Comet 2 is @ 28 months follow up vs @ 21 months follow up for the primary OS endpoint in Comet 1. Given the basic similarities in patient groups, this little bit of "wiggle room" in trial design might actually tease out a borderline OS benefit that might take a bit more time to manifest. Sometimes time is your best ally. JMHO FWIW
I'm sure I'll stand corrected if wrong, but to the best of my belief, both trials are targeted toward FDA-approvable endpoints. With that said - commercial success can only truly be realized with a clinically recognized overall survival advantage. A pain relief benefit is considered approvable, but it most likely would not not advance Cabo any further in the treatment algorithm than a late-stage refractory patient population.
Which - for my money - would be better than no approval at all...
Current update claims 69 of 84 either recruiting or active, no longer recruiting.
15 site locales are listed as not yet recruiting. Seems slow to me...
Makes me wonder if there's a connection between the slow recruitment and the short play enabling the convertible tango. It might help account for a run of closings below the $6.90 target.
Wash Rinse. Repeat. The cycle does persist, does it not?
So many "what-ifs" to consider in such an advanced patient group - sick enough to qualify for trial and having survived the toxicities of at least one line of chemo - and yet another of hormone therapy...and (hopefully) healthy enough to live long enough to realize the benefit of whatever therapy Cabo may confer - in what appears to be a remarkably short treatment period. No wonder there're so many shorts on board !! I guess we'll soon find out if the recruiters did their job well enough. Thanks for the spin, Hbomb.
More good juice on bony mets in CRPC. Pubmed 3/13/14...Tait C et al...
"Quantification of skeletal metastases in castrate resistant prostate cancer predicts progression free and overall survival."
More good news on the BM front...
Jonesy: wrt Dydees, don't leave home without 'em...
Bif...just found this...check it out at Biomarker Commons..posted 1/17/14 from PR Newswire.
"Surveyed Oncologists Indicate that the Use of Biomarker Testing is Increasing Rapidly in Non-Small-Cell Lung Cancer in China and South Korea"
I suspect that - in an evolving world clinic of target-specific therapeutics - assays will find a way.
It is...but that's the whole point...and it's the hallmark bane of biotech.
Periods of no news coupled with high short interest.
I like to think of it as the final dip before the royal rip...
This is a bit reminiscent of when we were stuck between $4.50 and $5.30...
Rangebound again while the hedges try to wear us out...
Make no mistake...this is nothing more than a ploy to exorcize shares from weak players.
Shakin' it here, Boss...
"Background: Cabo is a multitargeted kinase inhibitor that has demonstrated complete and partial responses in mCRPC as assessed byTc-99 MDP bone scintigraphy. FDG and FDHT PET/CT demonstrate glucose metabolism and androgen receptor binding, respectively. We are exploring these tracers as response biomarkers in mCRPC treated with cabo. Methods: Patients (pts) treated with cabo were scanned with FDHT and FDG PET at baseline and after 6, 12, and 24 weeks (wks) of treatment. 5 index lesions were selected at baseline for each PET modality. The hottest slices from each were averaged (SUVmaxavg) and measured on post-treatment scans. The concordance of the post-treatment alterations of the two tracers (rise vs. decline) was examined, as were PSA alterations. Results: All 16 pts had FDG avid and 15 had FDHT avid disease. Baseline median FDHTmaxavg was 10.84 (3.52 – 18.52) and FDGmaxavg was 6.26 (2.74 – 14.7). Post-treatment alterations are described (Table). Conclusions: Most pts with mCRPC demonstrate diminution of FDHT uptake after 6 and 12 wks of treatment with cabo. These declines are matched by FDG 50-60% of the time, and correlate with PSA declines even less frequently. The etiology of the extent and degree of FDHT declines, and lack of concordance with post-treatment PSA changes, warrant further investigation, and correlation with other imaging modalities and clinical outcomes. Clinical trial information: NCT00588185."
Best have some fresh Dydees close at hand, Jonesy. Yer gonna need 'em...
"Post-treatment alterations in 18F-dihydrotestosterone (FDHT) and FDG PET/CT in metastatic castration-resistant prostate cancer (mCRPC) treated with cabozantinib."
JJ Fox, ASCO 2013....
If I read this correctly,I believe these two studies improve the odds of successfully handicapping Comet 1.
"Bone Metastases in CRPC:::" Pubmed Nov 2013 Vargas, Scher, et al...
Not just associated - but "significantly" associated.
"Conclusion In patients with castration-resistant prostate cancer, numbers of bone lesions on CT, FDG PET, and FDHT PET scans and the intensity of FDHT uptake are significantly associated with overall survival. © RSNA, 2013."
Hbomb, Ernie, Joeflow, Bif...any comment appreciated...
One of the LC docs I keep on my activities watch list, Dr Mark Kris, has made noteworthy contributions to the growth and viability of the USLCMC. The entire concept of effective targeted therapy is reliant on the development of a mutation - specific assay. As in many other techno-endeavors, it will not likely be cost-effective at first...but make no mistake - it's time is at hand. As in many other cancers, mutation - specific treatments are coming of age in LC. I've mentioned it before, but I don't mind saying it again...
Cabo could sure use a CDX biomarker assay, and I feel that this is also imminent.
Journal of European Urology March 2014...Rana Mackay, T. Choueiri, et al. Solid study, well written...creating further ties between metastatic site analysis and disease progression prognostics. The excerpt below - of course - encouraged me to give it a mention:
"Given these emerging data, it is also not too far-fetched to imagine the site of metastatic disease as a potential predictive factor for benefit from specific agents in the future (eg, cabozantinib may be most effective against bone metastases). Understanding whether a specific effect against a specific site is due to the amplification of a given pathway in this site of disease would be of great value."
A quick MB search advised me this had not been posted. If it's somehow a repeat, my apologies...
Found it in the magazine "European Urology" Nov 2013...M Xie, et al...
"Dual Met/VEGFR-2 inhibitor foretinib overcomes acquired resistance to sunitinib in metastatic renal cell carcinoma (mRCC)"
"...and there are a few hints that there is something hinky with the data set."
I've said it before. Ernie-if yer not already-you oughta make a living doing this stuff. Great post!!!
In addition to the Metmab/ erlotinib trial discontinuation, there are a couple of interesting JCO early releases that have potential to impact EXEL share price...as well as the ongoing clinical perceptions of Cabo impact.
Doc Matt Smith, et al published results on the ALLIANCE trial "Zoledronic acid in csPC and Bone Mets"...
"Conclusion: In men with castration-sensitive prostate cancer and bone metastases, early treatment with zoledronic acid was not associated with lower risk for SREs."
Keep in mind, earlier applications of Cabo use are still being explored.
Doc Celestial Higano published "To treat or not to treat: Bone Targeted Therapy in mPC", which is not a freebie. I may tap the cookie jar at some point to access this one, as Higano has a lot history (both past and current) with Cabo, and I would consider her insights potentially invaluable.
Early bisphonphonate therapeutic benefit looks like a bust, and Cabo is only just beginning early combo trials with hormone axis therapeutics. Any hint of synergistic bone-targeted benefit may blow the lid off.
Just a reminder: the cancelled METMab study began recruiting in 2011. Cabo has seen use in combo with erlotinib for at least one additional year, and I suspect two years. In addition to which, since that early trial, there have begun two additional sponsored trials in combo with erlotinib in LC. The earliest trial has completed, and the latter two are as yet still enrolling. I think we're still looking good here.