Recently men with advanced prostate cancer have found that their insurance companies have been dictating what drugs they can get instead of their doctor making the best decision for them. At Malecare we have seen that when a man with metastatic castrate resistant prostate cancer (mCRPC) has finished taking chemotherapy they have been steered by some of their insurance companies to take Zytiga before Xtandi (Zytiga is a cheaper drug than Xtandi.) Both of these drugs are equally effective for these men, but their mechanism of action is entirely different.

In reality the only similarities between Zytiga and Xtandi are that both drugs are approved for use with men who have castrate resistant prostate cancer and who have had prior chemotherapy with any taxane based therapy like Taxotere (docetaxel) or Jevtana (cabazitaxel). Currently, Zytiga is also approved for use with a man who is castrate resistant and has not had any chemotherapy (there are ongoing trials designed to obtain a similar approval for Xtandi.)

Xtandi is an androgen receptor inhibitor that targets multiple steps in the androgen receptor signaling pathway in the tumor cell. In preclinical studies it: induced cell death, decreased cell proliferation and decreased tumor volume. Basically, it inhibits androgen binding to the androgen receptor; inhibits androgen receptor nuclear translocation and it inhibits androgen receptor interaction with DNA

Zytiga is an androgen biosynthesis inhibitor (ABI) that interrupts the androgen biosynthesis pathway by blocking CYP17 (17a-hydroxylase/C17 20-lyase). This results in the inhibition of androgen production at three sources of testosterone production, the testes, androgen glands and the tumor tissue. This androgen inhibition results in decreased levels of serum testosterone and androgens.

In addition to these very basic differences in method of action, Zytiga also requires the use of daily steroids (in the trial the steroid used was prednisone.) For some men like those of us also dealing with diabetes steroid use is not recommended, so Zytiga may not be a viable option to use.

Simply put, Xtandi prevents androgens from acting on and encouraging the growth of prostate cancer cells while Zytiga, along with prednisone limits the production of androgens which will would otherwise encourage the growth of prostate cancer cells.

Both of these drugs are very important for the treatment of men with advanced prostate cancer and both have a significant place in our treatment protocol. Neither drug has been shown to be superior to the other. Zytiga showed a survival advantage over placebo of 4.6 months while Xtandi showed a similar 4.8 month survival advantage over placebo. Both of these drugs improve a man’s quality of life.

So, given that both of these drugs are basically equal in efficacy, but both have a totally different mechanism of action, our insurance companies should not be serving as our doctor and make basic medical decisions about our health. Those insurance companies that have supplanted out doctors best medical judgement are only thinking of their own economic interests.

Step therapy has no place in medicine, including oncology, when it is solely based on economic savings. When there is a generic drug available, when a drug with the same method of action is available, when there is a drug that is superior or when there is a drug that is safer than another step therapy might be appropriate.

When these criteria are not met step therapy can cause unnecessary harm.

Joel T Nowak, M.A., M.S.W.