The abstracts for the forthcoming American Society of Clinical Oncology 2012 Genitourinary Cancers Symposium (ASCO GU) have been released and offer insight into some of the new data that will be presented at the meeting.
The As expected, there is no change to data presented in Stockholm that showed radium-223 (Alpharadin) improves both Overall Survival and Skeletal Related Events:
radium-223 Overall Survival Benefit
median 14.0 vs 11.2 months; P value = 0.00185; HR = 0.695
radium-223 time to first SRE
median 13.6 vs 8.4 months; P value = 0.00046; HR = 0.610
However, the meeting abstract published today shows that radium-223 in bone-metastatic castration resistant prostate cancer patients (CRPC), not only significantly prolonged time to first skeletal related event (SRE), but significantly prolonged 3 out of the 4 SRE components:
- time to spinal cord compression,
- time to pathological bone fracture
- time to external beam radiation
No significant improvement in the SRE component of time to surgical intervention was seen with radium-223.
The data from the abstract is summarized in the following table:
| SRE Component | Ra-223 % of Events (n=541) | Placebo % of Events (n=268) | Time to Event (Ra-223 vs Placebo) P value | Time to Event (Ra-223 vs Placebo) HR (95% CI) |
|---|---|---|---|---|
| Pathologic Bone Fracture | 3.6% | 6.7% | .013 | .45 |
| Spinal Cord Compression | 3.1% | 6.0% | .016 | .44 |
| External Beam Radiation | 22.6% | 26.9% | .0038 | .65 |
| Surgical Intervention | 1.7% | 1.9% | .69 | .80 |
The spinal cord compression benefit has a lot of clinical significance given that it can lead to paralysis.
Oliver Sartor (Tulane) will be presenting the above data at ASCO GU. The abstract concluded that:
Radium-223, a novel alpha-pharmaceutical, may provide a new standard of care for the treatment of CRPC patients with bone metastases.
A new treatment option such as radium-223 is good news for the many elderly patients who are unfit for chemotherapy and have metastatic prostate cancer that has spread to their bones.
I look forward to seeing more data on the effect that radium-223 has on quality of life and bone pain in this patient population. radium-223 Alpharadin is on fast-track for FDA approval this year.
Update February 1, 2012
The radium-223 data will be presented at ASCO GU by Oliver Sartor, M.D., who is Medical Director of the Tulane Cancer Center, C.E. and Bernadine Laborde Professor of Cancer Research and Professor, Department of Medicine: Section of Hematology & Medical Oncology and Department of Urology.
Dr Sartor kindly provided the following additional perspective about radium-233 and the clinical significance of the data that he will present:
What is the clinical significance of the skeletal related event data that you will present?
I think the clinical significance of the SRE data are high…. radiation to bone, fractures in bone, and spinal cord compression are all clinically relevant events and all are decreased significantly in the Rad-223 arm. These are NOT simply xray findings or morphometric fractures which are included in the denosumab trials.
Is there any data on pain & quality of life (QoL) for radium-223?
The pain and QOL data for Rad-223 has not been completely analyzed but the significantly less radiation to bone as an SRE component clearly implies less bone pain, as that is the typical indication for radiation to bone.
How does the radium-223 data compare to denosumab in its ability to delay skeletal related events?
Denosumab does not extend survival but Rad-223 clearly does.
It is hard to compare SREs precisely as the definitions differed…. Rad-223 excluded the skeletal xray finds that denosumab included.
Dr Sartor’s clinical perspective clearly shows the excitement and potential for radium-223 (Alpharadin) in advanced prostate cancer. I appreciated that he took the time to respond to my questions despite a busy clinic and traveling to San Francisco.
Is Alpharadin better than Xgeva? In my opinion the fact that Alphardin has shown an overall survival benefit is huge. It will certainly make for an interesting ODAC on February 8th when Amgen’s Xgeva prostate cancer approval will be reviewed.
Erratum March 6, 2012
I was not at the ASCO GU symposium in San Francisco, but it appears from the ASCO Virtual Meeting & a subsequent ASCO Post article, that Dr Parker presented the ALSYMPCA data at the meeting rather than Dr Sartor as I previously wrote.
Dr Sartor is an ALSYMPCA trial investigator and was one of the co-authors on the ASCO GU paper. He undertook the pre-meeting media briefing on the updated Alpharadin data which is where the confusion arose. It was not clear (at least to me) that he was substituting for Dr Parker and I wrongly assumed he was presenting the data at ASCO GU.
Apologies for my error.