There is a lot of cross-resistance in all these medicines targeted at the androgen receptor (AR). Darolutamide is not approved for metastatic CRPC, although it probably works as well as any of the other second generation anti-androgens. Apalutamide and darolutamide are supposed to prevent AR upgrading. There have been no comparative tests yet.
Thanks for your reply. I should note that darolutamide is approved for lymph node metastasis, as long as it's local or regional. (In their Phase III study for FDA, theysimply didn't include lymph nodes; made it sound like they weren't doing mets of
any kind. But FDA did approve daro for lymph node mets.)
When you say cross-resistance, what exactly do you mean? If one fails, does that
Yes, you are right that Nubeqa is approved for any non-M1 CRPC. Yes, cross resistance means that once the cancer is resistant to one, the others will not work for very long.
You could discuss having a direct biopsy if possible or a liquid biopsy to study the genome of the cancer and do immunohistochemistry analysis (IHC) to see if there are specific mutations and / or markers which could make the cancer susceptible to treatments with drugs such as olaparib, rucaparib, keytruda or chemo with platinum compounds (cisplatin, carboplatin etc.).
In broader sense, Anti Androgens have similarities ...They all block DHT/T from activating Androgen Receptor and thus, deprive the cancer cells of essential substance they need to divide and grow.However, there are many differences...when it comes to side effects. e.g. Bicalutamide causes least heart related side effects whereas Abiraterone causes most cardiac side effects.
Studies have shown that risk of major cardiac side effects are 1% in placebo group, 2% in Bicalutamide group, 6% in Enzalutamide group and 14% in Abiraterone group.
And Enzalutamide causes seizures in some men. Darolutamide and Apalutamide are too new to really know about their side effects.
As for cross resistance....Not a 100% phenomenon. There are cases where men who failed Bicalutamide but then responded to first generation meds like Flutamide.
One of the main mechanism of resistance is androgen receptor amplification..meaning that now a stronger Anti Androgen is needed to have same effect...so once Bicalutamide fails..it makes sense to upgrade to Enzalutamide as the later is stronger AR blocker albeit with more side effects.
Bicalutamide generally does not have cross resistance and closes no options. Abi and enza have a degree of cross resistance (take abi before enza to lessen it).The newer lutamides are too new to tell.
Content on HealthUnlocked does not replace the relationship between you and doctors or other healthcare professionals nor the advice you receive from them.
Never delay seeking advice or dialling emergency services because of something that you have read on HealthUnlocked.