Fulvestrant or cdk4/6 inhibitors ?

[Lindoky]

hello

I’m curious , how do you know which treatment failed you since pet shows progression. For example if you’re taking fulvestrant with Kisqali and you have progression , is it normal to just switch the cdk4/6 inhibitor or the fulvestrant . I’m interested to know if anyone stayed on fulvestrant or letrozole and only switched the cdk4/6 inhibitor and then showed good results on next scans or improvement / stability ?

[bikebabe]

I don’t know either as haven’t reached point where scans have indicated anything - but I have lobular bc which is hard to detect. Blood tests for gene mutations/variants eg esr1 may throw up some info to support a change of hormone or cdk. But I don’t know if these are done routinely (in uk).

[MadameKa]

I can't answer your question but I am very curious. I was on palbociclib and letrozole for several years and when that combination ceased to be effective I thought it would be logical to try swapping one and then the other to see which element is no longer working. However, I live in the UK and the protocols in the health service are rigid so we could only proceed by changing both.

[Dragonfly2 in reply to MadameKa]

The same happened to me when testing showed I now have the Pik3CA mutation. Hence the change to Piqray snd fulvestrant. If this fails I don’t really know what is next. ❤️‍🩹.

[TammyCross]

I would think the answer is that neither one is working. If either one is working, why would you have progression?

That is my first thought.

My second thought is that it is the fulvestrant that is the "heavy hitter." The CDK4/6 inhibitors just amplify the effect of the estrogen inhibitor. Fulvestrant is very effective, when it works. You can switch out the CDK4/6 inhibitors (Kisqali has been shown to be the most effective), but finding a SERD or AI that works is most important.

[Dragonfly2 in reply to TammyCross]

Tammy you are so clear in your thinking! Makes so much sense! Thank you !

[HelenWi in reply to TammyCross]

That is also my understanding , that the hormone blocker or receptor degrades are the key drugs. But… I think that switching the other drug must make a difference. For example, going from ibrance to Piqray and keeping Fulvestrant. I don’t know that the oncologists understand all that unless they run trials and do research.

[TammyCross in reply to HelenWi]

Piqray is a targeted therapy, but in my reading, it does more than enhance the other medication. It is specific to one mutation, and is used in combination with fulvestrant only (yes, probably that is how they tested it). It is not used with AIs.

[TammyCross in reply to HelenWi]

I think that is different. Piqray is targeted, but it works independently if one has a particular mutation.

[NShaft]

It might be a good idea to have a liquid biopsy for any mutations after progression. The results would help you decide on the next treatment.

[Gingerann1]

Hi Lindoky:

I am still on my first line treatment with Ibrance and Fulvestrant and at my last appt there was a discussion if and when there is progression (NED 3 yrs now) that they would do a guardant test to see what next med would be appropriate based on mutation although previous discussions indicated that the CDK would be replaced, not Fulvestrant that was considered “ the heavy hitter” at least for me.

[Lulis]

I'm on Letrozole and Ibrance. I was told if I have progression, I would not get another CDK drug because I have the PIK 3 mutation. I think Piqray would be next, but she did mention doing a liquid biopsy at that time.