Most of the newly approved drugs and treatments for men with advanced prostate cancer are designed and approved to be used independently of other advanced prostate cancer treatments, other than with the continuation of standard androgen deprivation therapy (ADT). The newly approved drug, Xofigo, is different. It has been designed to supplement, or actually go along with what is referred to as the Best Standard of Care.
The phase III clinical trial named the ALSYMPCA was the trial that led to the FDA approval of Xofigo. It was a randomized, double-blind, placebo-controlled international study of the use of Xofigo with best standard of care vs. placebo with best standard of care in symptomatic CRPC men with bone metastases. The trial enrolled 921 men in more than 100 centers in 19 countries. The study treatment consisted of up to six intravenous injections of Xofigo or placebo, depending upon the arm of the study the man was in, each separated by an interval of four weeks. The operative words here are: “with the best standard of care” for both men in the investigational arm and the placebo arm.
This is different than in other trials that were used for the approval of all the other newly approved treatment modalities for men with advanced prostate cancer. These other trials never included the “best standard of care.” So, this means that Xofigo is designed and its FDA approved label requires it to be used along with the “best standard of care.”
At the time that the ALSYMPCA trial was designed (many years ago) the best standard of care included localized EBRT, corticosteroids, anti-androgens, estrogens, estramustine or ketoconazole. The on-label approval for Xofigo includes the concurrent use of these other mentioned treatments. Xofigo is not designed to be used independently of these other treatments.
Time marches on and many of these “best standard of care” treatments are no longer the best standard of care. So, what are a doctor and patient to do? Clearly, cutting edge doctors are going to experiment and use the newer drugs with similsr mechanisms of action, perhaps use Zytiga or Xtandi in place of the old, out dated “standards of care.” Those doctors who are not has studied or not as specialized in the treatment of advanced prostate cancer will probably use Xofigo as a single agent despite the lack of evidence that it will help when administered as a single agent.
At ASCO 2013 there was a lecture that warned about the use of Xofigo along with chemotherapy. One doctors experience was that this particular combination is too toxic to be combined. However, I am aware that there are other doctors that have not had this experience. My recommendation is that if you do combine Xofigo with chemotherapy have your doctor VERY CAREFULLY monitor the toxic effects you experience. If they become very severe let your doctor know immediately or go to the emergency room.
Men with Crohn’s disease, ulcerative colitis, prior hemibody radiation or untreated imminent spinal cord compression were excluded from the study and are not “on label” candidates to receive Xofigo. Additionally, men with bone fractures should have orthopedic stabilization performed before starting or resuming treatment with Xofigo.
Xofigo is different than the other newly approved treatments for men with advanced prostate cancer or castrate resistant prostate cancer. Please make sure that your doctor fully understands the use of this new and powerful treatment option.
Joel T Nowak, M.A., M.S.W.