According to a media release issued this morning by Exelexis, Inc. (a San Francisco-based biotech company), a development stage drug, XL184, has shown clinically significant effects in an early stage clinical trial in men with metastatic, castration-resistant prostate cancer (mCRPC).
These are interim data from a small, ongoing, non-randomized, Phase II clinical trial that has enrolled 99 patients in total to date. So they need to be interpreted with caution. The full data set is being presented today at a poster session at the 22nd EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Berlin, Germany.
The basic results reported by Smith and his colleagues on behalf of the clinical research team are as follows:
- 19/20 patients (95%) with evident bone metastasis achieved either complete or partial resolution of their lesions on bone scan after independent review.
- Most such resolutions had occurred within just 6 weeks from initiation of therapy.
- Resolution was evident in docetaxel-pretreated and in docetaxel-naïve patients.
- Bone scan resolution was associated with investigator-reported improvements in bone pain, and the majority of symptomatic patients experiencing pain relief.
- Patients with anemia at baseline exhibited maximal increases in hemoglobin levels ranging from 1.2 to 3.4 g/dl from baseline.
- Tumor shrinkage was observed in 38/55 patients (69 percent) with measurable soft-tissue metastatic lesions and at least one post-baseline scan.
- 3/34 patients (9 percent) evaluable by RECIST criteria achieved a confirmed partial response (PR).
- Stable disease (SD) was reported in 25/34 patients (74%) including 2 unconfirmed PRs.
- Safety data are available for 49 patients who had at least 6 weeks of follow-up.
- The most common adverse events of grade 3 or higher, regardless of causality, were fatigue (14 percent), hypertension, PPE syndrome (each 6 percent), hemorrhage, nausea (each 4 percent), diarrhea, cough, and rash (each 2 percent).
It should be noted that these are a potentially serious spectrum of significant side effects which could be problematic (unless XL184 is subsequently proven to be associated with a long survival benefit). It should also be noted that the effects of XL 184 on shrinkage of tumors to bone and soft tissue do not appear to correlate in a reliable manner with significant declines in patients’ PSA levels.
Exelexis says that, “XL184, an inhibitor of tumor growth, metastasis and angiogenesis, simultaneously targets MET and VEGFR2, key kinases involved in the development and progression of many cancers.” The company has also suggested that a randomized Phase III clinical trial of XL184 in mCRPC might begin some time in 2011. The “New” Prostate Cancer InfoLink suspects that some time in 2012 is perhaps more realistic. However, these are interesting preliminary data from a trial of an investigational drug that works very differently than any other agent currently in clinical trials for treatment of men with mCRPC.