Zoledronic Acid did not prevent bone mets in high risk Prostate Zeus trial
"The ZEUS trial included 1,433 men with high-risk prostate cancer defined as a PSA score at diagnosis of 20 ng/dL or higher, a Gleason score of 8 to 10, or lymph node positivity. Patients were randomly assigned to treatment with 4 mg of zoledronic acid every 3 months for 48 months (n = 716) or to the control arm (n = 717).
Patients in the zoledronic acid arm were followed for a median of 4.7 years, and patients in the control arm for 4.8 years. No difference in the rate of bone metastases was found between the two groups at the end of follow-up (13.7% for zoledronic acid vs 13% for control)."
In addition... "no difference in overall survival between the two arms was noted."
Makes me wonder about the potential for Cabo as an adjuvant to existing bone mets treatments...
Matt Smith has said Cabo is the best bone agent he's ever worked with; indeed it showed sclerotic healing in the NRE trial he ran. There's a chance we'll see Cabo being used in the non-oncologic indications that Zoledronic Acid and Denosumab are used in today many years down the road.
In addition, I found the following commentary on The "New" Prostate Cancer Infolink:
"Dr. Philip Saylor of Massachusetts General Hospital in Boston, asked by Medscape to provide expert perspective on this study, did find a positive comment to make about the results of what was otherwise a negative trial, stating that
The ZEUS results affirm that we are well served to reserve the use of potent osteoclast inhibition — with either zoledronic acid or denosumab — for men with prostate cancer that is already metastatic to the bone and has progressed on first-line androgen-deprivation therapy.
Saylor also expressed his opinion that,
Rather than preventing bone metastasis, zoledronic acid and denosumab have both been shown to significantly reduce the incidence of skeletal events, such as pathologic fractures and spinal cord compression, in prostate cancer patients with advanced disease.
He continued by observing that:
Intensive osteoclast inhibition with monthly denosumab has been shown to modestly prolong metastasis-free survival by about 4 months in men who have progressed on first-line androgen-deprivation therapy. Denosumab was notably not approved for this indication for a number of reasons, including the absence of an effect on overall survival."
Great posts - but doesn't this just highlight the importance of achieving a positive OS result? Going into ASCO, I think the OS results from MTC may have a pivotal effect - as many doctors seem to think the therapeutic benefit for pain is about as good as nice massage. Makes me a bit nervous.
Great post. Is it me, or should the bone healing effects of Cometrique be getting just a bit more valuation respect? Is there not considerably more evidence today than in the fall of 2010 that the "bone scans" aren't just a curiousity. Put aside the need for greater clinical evidence of the who, when, and where, Cometrique will best be utilized for metastasis to the bone. The clinical need to understand it better is a given. But the valuation situation reminds me of Louis CK's bit about "everything is wonderful and nobody is happy" (google it, very funny) describing peoples appreciation or lack thereof for air travel. We should be exclaiming "holy #$%$" everytime we see an image of the amazing effect Cabo has on bony mets.