Evolutions in the treatment of nmCRPC — redux

So at the Genitourinary Cancers Symposium in San Francisco today we were presented with full reports on the SPARTAN trial and the PROSPER trial by Drs. Eric Small and Maha Hussain, respectively.

In addition,

  • The full results of the SPARTAN trial were published on line today (by Smith et al.) in the New England Journal of Medicine.
  • Dr. Phillip Kantoff provided his personal assessment of the data from these two trials and the implications for their potential use in the treatment of nmCRPC.

Here is where your sitemaster has “netted out” after hearing the full data presentation for both trials; reading the article in the NEJM; and listening to Dr. Phillip Kantor’s commentary on the data from the two trials:

  • Within the next 6 months or less,
    • Apalutamide will get FDA approval for the treatment of non-metastatic catsration-resistant prostate cancer (nmCRPC).
    • Enzalutamide with also get FDA approval for the treatment of nmCRPC.
  • There are currently no compelling reasons to believe that one of these drugs is categorically “better” than the other for the treatment of nmCRPC; however, …
  • It is certainly possible that some patients with nmCRPC will respond better to one of these drugs than the other, but …
  • There is currently no way to identify those patients prior to treatment.
  • Both manufacturers (Johnson & Johnson for apalutamide and Medivation/Astellas for enzalutamide) will spend a small fortune on trying to make physicians and patients think that their drug is the better of the two.
  • We don’t have any compelling data (yet) to support the idea that either drug will confer a long-term survival benefit in men with nmCRPC.
  • Both drugs are very clearly “effective” in the treatment of nmCRPC.
  • Both drugs have similar levels of adverse events, but the adverse events are somewhat different.

Your sitemaster can also tell you that if he was to be diagnosed with nmCRPC 48 hours after both of these drugs had been approved by the FDA, he would choose to be treated with enzalutamide (Xtandi).

Why? Because we have 5.5 years worth of “real life” experience and data on the side effects of enzalutamide. By comparison, we have very limited data on the “real life” side effects of apalutamide (outside of this single large clinical trial).

6 Responses

  1. Is there evidence that apalutamide is superior to abiraterone + prednisone by any endpoint?

  2. Rick:

    There are no data comparing apalutamide to abiraterone acetate + prednisone. The manufacturer (Johnson & Johnson) of these two agents has very carefully avoided any such comparison.

  3. Or a difference in cross resistance as there certainly is between abiraterone and enzalutramide. Something with less resistance overlay would be nice.

  4. Dear Tarhoosier:

    Since all of the men in the SPARTAN trial of apalutamide were given the option of follow-up therapy using abiraterone + prednisone once they progressed on apalutimide or on placebo (in order to minimize the likelihood that they would then get enzalutamide), we have no data yet on the question of differential cross-resistance.

  5. Since J&J has avoided comparisons, that leads me to think their new drug apalutamide is not superior.


  6. Dear Lowell:

    I think that you need to appreciate that apalutamide is much more like enzalutamide (Xtandi) than it is like abiraterone acetate (Zytiga). From a business perspective, what J&J would like to be able to do is have apalutamide replace enzalutamide. If they can do that while Zytiga is still on patent, they can then afford to see whether apalutamide is “better” than abiraterone acetate later.

    In general, I’d be surprised if any of these drugs is actually much “better” or “worse” than each other. However, they may each be “better” for certain subsets of patients who still need to be better defined.

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