Intervening Earlier to Prevent the Consequences of Bone Metastasis
In patients with metastatic castration-resistant prostate cancer (mCRPC), treatment with radium-223 has demonstrated a survival benefit, regardless of prior docetaxel use, and positive impacts on symptomatic skeletal events (SSEs) and quality of life. It has also been recognized that the use of radium-223 later in the sequencing paradigm may limit the number of patients able to receive the full 6 cycles of treatment. Several large randomized phase 3 clinical trials of combinations of abiraterone, enzalutamide, radium-223, and other novel agents are ongoing. In the interim, there is a lack of level 1 evidence to guide therapeutic sequencing. Nonetheless, the case for an approach that includes the early targeting of bone metastases is strong: advanced prostate cancer predominantly resides in the bones, and metastatic bone disease is associated with SSEs, worsening health-related quality of life, and increased mortality.
Co-Director, Urologic Oncology
As someone who delivers a lot of radium-223, I’m sometimes frustrated that, when a patient is referred to me bed-ridden and heavily pretreated, no one ever really gave a thought to using radium early. We know from the original ALSYMPCA (Alpharadin in Symptomatic Prostate Cancer Patients) trial that only about 58% of patients got all 6 infusions. When I see a patient who is heavily pretreated, I know I am not going to be able to give him all of the medication. If I see someone who is early on in the process – where he has early symptomatic castrate-resistant prostate cancer (CRPC) and some metastases – that is the type of patient I think we can have the greatest impact on. We’ve seen some studies now indicating that asymptomatic patients were more likely to have a better prognosis and a longer disease-free survival, or rather, secondary skeletal event symptoms, as well as overall survival. Then there’s also some interesting laboratory evidence suggesting that radium-223 may impact the cancer cells so that they can be more susceptible to T cell-mediated lysis. That interaction, although we’re going to need the bigger studies to see how to combine these drugs, supports earlier intervention in symptomatic patients, where it’s appropriate, and is something that we should be shifting toward.
“With regard to when to treat with radium-223, if I see someone who is early on in the process – where he has early symptomatic CRPC and some metastases – that is the type of patient I think we can have the greatest impact on.”
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