Zytiga or Xtandi? : Next month, my... - Advanced Prostate...

Advanced Prostate Cancer

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Zytiga or Xtandi?

leebeth profile image

Next month, my husband will be started on a 2nd gen anti androgen.

Are there any specific reasons to prefer one over the other, from a medical standpoint?

We are currently on commercial insurance, and Zytiga would have a copay of $50 a month and Xtandi would be free.

After we go on Medicare next year, we would have a 20% copay for Zytiga, with an annual out of pocket cap of $3960. Xtandi would be free.

My husband does not have a history of seizures or cardiac disease, but he has a slightly fatty liver and his liver enzymes are pushing the upper limits of normal.

If we are eventually going to cycle through both of these drugs, maybe starting with Zytiga would be better? Thoughts?

13 Replies

Zytiga and Xtandi work by different mechanisms. In simple words, Zytiga is a testosterone blocker whereas Xtandi is an Androgen receptor blocker. AR blockers work by not allowing T/DHT to promote cancer growth.Zytiga blocks all 3 sources of androgens and thus, potentiates the androgen deprivation whereas Xtandi just blocks the receptors where Androgens work. My point is that they are different and both are still effective. The choice requires all the details of a particular case to make a good decision as to which one is more suitable.

leebeth profile image
leebeth in reply to LearnAll

And, of course, one doc prefers one and one the other! Thank you.

There is a definite advantage starting with Zytiga and then moving to xtandi if/when Zytiga fails. I just finished my course of zytiga so I can tell you for me the SEs were tolerable but I do notice a difference now that I'm off zytiga.

leebeth profile image
leebeth in reply to TomTom1111

Thank you! He has tolerated chemo well, so I am hopeful.

Hi leebeth,

Here is a meta-analysis of the best sequence for Zytiga [Abiraterone] and Xtandi [Enzalutamide]: [1].

"Seventeen studies met the inclusion criteria."

"Conclusion: Significant clinical efficacy of AAP {abiraterone acetate plus prednisone} administered as the first-line treatment in mCRPC patients followed by enzalutamide, delaying disease progression, compared with the ENZ → AAP sequence. However, more studies and randomized trials are needed, to validate the best treatment sequencing."

Note that the patients (all metastatic) were resistant to first-line treatment [mCRPC].


[1] pubmed.ncbi.nlm.nih.gov/334...

leebeth profile image
leebeth in reply to pjoshea13

Thank you. He is still hormone sensitive but there seems little reason to believe this would be different!

There was a small sequencing randomized clinical trial.

The sequence Zytiga -> Xtandi lasted 19.3 months until PSA progression

The sequence Xtandi -> Zytiga lasted 15.2 months until PSA progression


If PSA progression translates to a survival improvement, then Zytiga->Xtandi is the preferred sequence.

Usually, generic Zytiga is less expensive than Xtandi. But cost consideration may be different for you.

leebeth profile image
leebeth in reply to Tall_Allen

Thank you. Yes, Xtandi is free for us, but I don’t want cost to be the reason. We prefer no progression and cost is secondary. Thank you!

Zytiga could be hepatotoxic in some patients, leading to discontinuation of treatment.


"Hepatotoxicity: Increases in liver enzymes have lead to drug interruption,

dose modification and/or discontinuation. Monitor liver function and

modify, interrupt, or discontinue ZYTIGA dosing as recommended. (5.3)"

Xtandi is not associated with liver problems:


leebeth profile image
leebeth in reply to tango65

Yes, that is one of my concerns. I would also like him to switch from degarelix to Orgovyx, but waiting on that until established on 2nd gen

What 1st gen anti androgen has he been on? It might make a difference in his choice.

leebeth profile image
leebeth in reply to Magnus1964

He is on degarelix but I would like to switch to Orgovyx. I thought we should get him established on the 2nd gen before switching.

tango65 profile image
tango65 in reply to leebeth

Enzalutamide has good results in castration sensitive cancer. This is a link to the randomized control trial,


Fig 2 and Fig 3 give an idea of the effectivity of this drug. Fig 2 shows that the median radiographic free survival has not been reached at 27-30 months.

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