Any have some hormonals fail then get long success with another?

dorimak

I started and got two years on Ibrance & Femara. Scan in April showed progression and switched to Faslodex. Last scan showed progression and I've switched to Affinitor and Aromosin. I had hoped to get longer from Faslodex as I'd heard some were on it a long time, but MO said Faslodex doesn't last that long. I wondered now that I'm on my third protocol can I hope for just months or could i possiblyget a longer run with this combo.

sandilee

Yes! Tamoxifen, Letrozole, Aromasin, Ibrance all failed me. But I've had great luck with Faslodex (3 1/2 years) and the Verzenio/Faslodex combo that I'm taking now. Our cancers are unique to us, and some drugs work better on some people than others. The Foundation One test that I recently took showed that my cancer would respond to Faslodex as well as Verzenio and Ribociclib, but not the regular AIs because of the specific pathways that they block.

dorimak

Sandilee, that is very encouraging. I'm also happy to see that it's been over seven years since your diagnosis. I do understand that we are all unique. Your Foundation One testing is interesting. I had never heard of it. I am attending a cancer center in the Midwest who have a strategic partnership with MD Anderson so am going to ask about it. I was disappointed that Faslodex didn't last long for me. It was very tolerable for me other than fatigue and I loved not having to think about taking pills every day. Thanks for your response and I wish you continued success and healing.

Cure-ious

Interesting question! I am also so encouraged by SandiLee's success, esp as we share a similar cancer subtype (Er+PR-), so hope I can be like you! It seems you started on just Faslodex alone? My question is can you get Foundation One sequencing and testing if the progression remains only in bones, or do you have to wait for tissue mets? Or are there circulating tumor cell assays available now? And with bone progression, can they radiate or do they have to move to the next treatment. My oncologist has indicated that she just moves to Faslodex alone for secondline, but the trials indicate a PFS of only about six months, so its not surprising, Dorimak, that you progressed so fast. And for SandiLee, the second try of faslodex was with a CDK4,6 inhibitor and it came after some chemo, so the cancer was exposed to different things that allowed the estrogen-dependence to re-emerge. This is why it is so helpful to be able to see the different sequence of treatments. So, SandiLee, you are about 71/2 years since diagnosis and have been on Abemaciclib and Faslodex for the past six months?! That is very heartening, that the side effects must be so much less than on chemo and you can be on such a treatment when you are years from diagnosis. Plus there are other treatments you have not tried yet, like the Alpelisib, and somehow you avoided the Aromasin-Affinitor? (good job!!), a CDK12 inhibitor, Venetoclax, and the others working their way into the system. Plus immunotherapy when they figure out a combo that works. Sandi, what does your oncologist say about how well you are doing? You must be his/her star patient!! Do you seek out a second opinion at every change?

From what I have read, estrogen resistance arises due to PI3K mutation about 40% of the time, and from ESR1 mutations about 27% of the time (or both are also common), and due to conversion to HER2-positive about 20% of the time, with triple-negative and triple-positive and other changes (FGFR) etc also possible but with lesser frequency. So it would be important to sequence to know why the cancer has progressed, especially wouldn't it be great to discover it mutated to HER2-positive and now you can take all of those other drugs?!

SandiBeach57

Cure-ious, what is your opinion about the Afinitor (mTOR inhibitor) plus fulvestrant combo to attack the p13K mutants?

I have put Alpalisib and fulvestrant on my growing list of possible treatments.

http://www.ascopost.com/issues/december-25-2016/fu...

Cure-ious

Sandi, Whenever its fulvestrant used alone as second line, the study usually shows about a 5-6 month PFS, which is too short for us! So the study you cite, adding everolimus, doubles the fulvestrant response to 10-11 months, which seems similar to the Alpelisib plus fulvestrant studies. And it seems they have applied to FDA for approval for Alpelisib, so that may soon be an option we can get from our own docs, not need to join a trial. Both drugs hit the same extended pathway (PI3K/mTOR) at different spots. Both drugs come with problematic side effects, but when we need to get that pathway, we have to choose something. I would favor starting Alpelisib just because of hearing the oncologists say they have the occasional patient who really responds well- my oncologist says she has patients who have also done very well on AA, but we haven't heard much of that on these boards. The rip on these drugs is they can do very well at the start but you don't get the long duration, and there was a study on the cell lines that showed they work a lot better if combined with an inhibitor to Aurora A kinase, so perhaps there will be a clinical trial start up using these drugs in combination, maybe combining at lower dosage if there is synergy, to make them more tolerable.

For these drugs to work best, the cancer should have PI3K mutation- but how do they determine that if they can't get enough material from bone mets to sequence? So I think we also have to watch out for circulating tumor cell or ctDNA analysis, so they can see if we need the drug and also use the tests to see more quickly if we are responding..

Daniel86

I dont know if this adds anything to the picture but keeping informed about trials in our area, I found out they have a trial right near us where Faslodex is being used with Letrozole for the first six months. The rational is that stopping AIs and moving onto Faslodex causes a slow but consistent new increase in estrogen levels that Faslodex basically cant counterinteract right away if not after 5 or 6 injections. Maybe thats the reason why if used by itself it allows cancer to progress that fast.

dorimak

Cure-ious, can I ask about the comment to SandiLee re good job on managing to avoid Aromasin-Affinitor? Is it because the side effects are so difficult? I tried to wade through the lengthy amount of info. on that thread but couldn't get a good sense. I started about two weeks ago and then got seriously ill with diarrhea and a high fever. Had to get IV fluids twice during the week. I was only on it five days and I'm off it for a week and just recovering with some cramping still on day 8 of being sick. The thing is I'm not sure if it was actually a stomach flu as there's one doing the rounds. The fever seemed like it might be an indicator. I see my MO on Tuesday. Just curious what you had to say about that combo.

JoE777

Dorimak I've been on Kisqali and Femara since April and the cancer has shrunk and in some places disappeared. I'm on a break fro the kisqali to see if the femara is enough. Your DX seems similar but I have grade 1. Keep asking. J