Cabo extends OS in heavily pre-treated mCRPC population as presented by Dr Scher at ASCO
Exelixis, Inc. (EXEL) today announced the presentation of updated interim data from 144 docetaxel-pretreated patients with metastatic castration-resistant prostate cancer (mCRPC) and bone metastases treated with cabozantinib in an ongoing non-randomized expansion (NRE) cohort of its phase 2 randomized discontinuation trial. Median overall survival was 10.8 months in a patient population in which 73% of patients had received two or more prior therapies including docetaxel and abiraterone, enzalutamide, and/or cabazitaxel. Furthermore, a retrospective analysis of the interim data shows that early responses in bone scan, circulating tumor cell (CTC) levels, and pain are associated with longer median overall survival (OS) as compared to non-responders. These post hoc findings, particularly the bone scan response results, support the rationale for potential future prospective validation of the association of bone scan response with OS in Exelixis’ ongoing phase 3 COMET trials in mCRPC. Howard I. Scher, M.D., Chief of the Genitourinary Oncology Service at Memorial Sloan-Kettering Cancer Center and a principal investigator on the study, presented the data today in a poster-discussion session at the 2013 Annual Meeting of the American Society of Clinical Oncology (ASCO) (Abstract #5026), in Chicago, Illinois.
“This clinical trial enrolled a heavily pretreated mCRPC population that has not been studied previously. These patients experienced disease progression despite treatment with docetaxel and additional therapies that included abiraterone, enzalutamide, or cabazitaxel. In this context the results are encouraging,” said Dr. Scher. “Patients with such advanced disease have limited options, and the data from this cohort suggest that cabozantinib has the potential to be an important treatment option for patients with mCRPC. The preliminary data suggest that these early response indicators are associated with longer median overall survival and warrant further prospective ev
At the Annual Shareholders meeting I talked to Gisela M. Schwab; about the 10.8 months O.S. rate.I said it didn't seem to excite anyone.She told me they were very pleased with 10.8 moths.That facts being the people were very ill and had been on many other treatments.
"These post hoc findings, particularly the bone scan response results, support the rationale for potential future prospective validation of the association of bone scan response with OS in Exelixis’ ongoing phase 3 COMET trials in mCRPC. "
This is particularly good news. The improvements Cabo has displayed in bone scan at 6 weeks and 12 weeks will become an early therapeutic witness of Cabo's uptake. You just can't beat bone lesion resolution, CTC reduction, and bone pain relief for hallmark biomarkers of therapeutic response. Doc Scher's many years of work wrt CTC enumeration as a surrogate trial endpoint for OS looks like it could eventually become an accepted component of future prostate trial design. I'd say Cabo's looking pretty darn good here...
Seems like it still comes down to the difference between "potential future prospective validation of OS" vs. "bone lesion resolution, CTC reduction, and bone pain relief" displayed in early bone scans.
The words "potential" and "prospective" seem to be just too open-ended and 10.8 months didn't exactly make anyone sit up and take notice when the abstracts were first published. Although Dr Scher points out that these patients have already tried everything else and have little or no other options(unmet need), "the preliminary data suggest that these early response indicators are associated with longer median OS and warrant further prospective evaluation in phase 3." So unless the FDA decides that the "unmet need" is greater than the current available treatment, it
seems to leave us exactly where we were before ASCO 2013, waiting for Comet 1 and 2 results in 2014. Plus, we now have the added burn of phase 3 for RCC, and although there seems to be an additional "unmet need", the added burn and the need for more cash seems to hang over EXEL like a "Sword of Damocles" . I'm still hopeful but am losing some patience. We will need some deep pocket help (a partnership) or a T/O pretty soon.