Cabozantinib in mCRPC: phase II results vs. expectation of III
Cabozantinib (XL184) in Metastatic Castration Resistant Prostate Cancer (mCRPC): Results From a Phase 2 vs. expectation of phase III
Results From a Phase 2: http://exelixis.net/sites/default/files/ASCO_2011-XL184-CRPC.pdf
Among 171 patients enrolled, 74 patients or 43% had prior treatments (Docetaxel-25%, Abiraterone/ MDV3100-5% & Other-13%).
Overall Progression-Free Survival and by Docetaxel Pretreatment Status (N = 154) after excluding patients randomized to placebo: 90 were Docetaxel-Naïve and the median PFS was 29 weeks. 64 were Docetaxel-Pretreated and the median PFS was 24 weeks.
1. Why would there be the expectation for COMET-1 to show overwhelming superior results in even sicker patients with metastatic prostate cancer no longer responding to docetaxel +Xytiga or docetaxel +Xtandi and be terminated early?
2. If COMET-1 can prove in the end that it can benefit this group of patients as the last hope, is it reasonable to speculate it will do well among man without pre-chemotherapy including those may eventually need Xytiga or Xtandi?
Thanks for earnest and logical responses and discussion!
The reason expectations were high was that before the trial was unblinded in phase 2 cabo group had median PFS of 23.9 weeks vs. 5.9 weeks with placebo. My concern with comet is everyone failed Zytiga or Xtandi to qualify for trial, as opposed to phase 2 where very few had received them. A decent idea in theory because cabo has to compete with prednisone instead of those drugs, but perhaps these patients are too sick for any drug to have a significant impact on mortality. A non-inferiority vs one or both of those drugs may have faired better. I'm long and confident in stock over next year but I'm afraid even if comet succeeds it may be fairly modest overall improvement in OS. Other indications for cabo and the potential for future trials as 2nd line rather than last line salvage therapy, as well as the compound they have partnered with Roche are reason enough to own the stock at these prices. Cash burn and potential dilution are my concern if comet fails.
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.
I am in Seattle and have never worked for Exelixis! Was s/he a decent person and good manager? I am looking for work now in bio-pharmaceutical industry and would love to get a job there since I have invested heavily in the stock.