Abemaciclib

mazie73

Hi all: I recently started a clinical trial at UC San Diego / Moores Cancer Center involving Abemaciclib (150 mg) + LY3023414 (a PI3K/mTOR inhibitor, 200 mg) + Faslodex. Unlike Ibrance, there's no week off — I'm taking the two drugs continuously, and am getting Faslodex injections monthly (except for the first round, which is doubled). I started on Feb. 4. While I'd like to say "so far, so good," I'm having a lot of gastrointestinal issues that come and go and don't seem to be tied to anything I've eaten. I'll have Mexican food one day with no problems and a very basic salad the next day and be curled up in fetal position all night, popping Tums.

Curious to know if anyone's tried Abemaciclib, with or without a PI3K/mTOR inhibitor — if so, what's your PFS? And, of course, curious to hear any tips and tricks to handling these stomach issues. While I'd like to be on this trial for a long time — I'll be kicked off if there's +20% progression — I'm also not thrilled with the random nausea, cramps and diarrhea.

Cure-ious

Hi Mazie,

Finally, we get to hear from somebody in one of the trials with a 2nd gen PI3K/mTOR inhibitor! I am curious why they suggested you start on a trial, rather than Ibrance/Faslodex? Perhaps its because the progression occured while you were taking Tamoxifen? The PI3K inhibitor is supposed to enable the cancer cells to reset; and become hormone-sensitive again, it should be an excellent treatment. Do you know if the trial accepts patients who have progressed following Ibrance/Femara? Very interested to hear about your experience, and what side effects they are seeing in the trial. Do you know whether you get all three drugs, or might you be getting placebo? Have you had blood sugar problems or mouth sores? Many thanks for joining us!

mazie73

Hi Cure-ious:

Glad I can be a resource / lab rat. My MO's original plan was Ibrance + Femara, but then a slot opened up in the clinical trial and she thought I'd be a good fit. You're correct about Tamoxifen: it didn't work for me. I was on it less than two years. It would have been 2.5 years, but I had to take a six-month break due to side effects.

I'm getting all three drugs. One group gets 200 mg of LY3023414 while the other gets 250 mg. I'm in the 200 mg group.

No mouth sores, but my sense of taste is a little dulled — similar to right after my second round of TC chemo. A little tired, too. I'm getting blood drawn on Friday, so I'll update you then. Also hoping to get some answers on these stomach issues. Meals today were: oatmeal, plain rice and more plain rice. Fun.

zarovka

cure-ious - I am hearing all over the place that Abemaciclib is working. I am guessing Mazie's doc thinks she'll do as well or better in this trial rather than the standard of care. She gets a performing CDK 4/6 inhibitor and hopefully the PI3K inhibitors works the magic and resets the cancer, as you have been saying.

Mazie - I am not on abemaciclib, but I am watching it closely. My understanding is that gastrointestinal issues are the norm on abemaciclib. I had heard that abemaciclib causes diarhea not cramps. It does mess with your gut.

The PI3K inhibitor side effects are somewhat undefined at this time.

It's clear that something is messing up your gastric system. Probiotics may be considered a supplement and not allowed on the trial. If they are allowed, take some. In any case, make yourself some homemade yogurt or buy high quality yogurt with live bacteria in it, drink kombucha and fermented drinks and research pre-biotics, which are really just foods that promote the growth of good bacteria. Gut health is your new mantra. Gut health is key to overall health as well as avoiding debilitating cramps. These drugs disturb the microbiome in your intestines.

We're very hopeful about adding PI3K inhbitors to hormonals. Adding a PI3K inhibitor to hormonals PLUS a CDK 4/6 inhibitor is potentially a lot of toxicity, but you have a very good shot at completely cornering the cancer and controlling it for a long time.

Best of luck. Hoping for frequent updates. Abemaciclib and PI3K inhibitors are front runners for the next break through in treatment protocols.

>Z<

Cure-ious

Hi Z! Here's another consideration about these drugs. In Maizie's case, where the mets developed on tamoxifen, the cancer had clearly become resistant, so its good to add in the PI3K inhibitor to try to reverse that. But if the mets developed off of therapy, as in my case, then some have argued that you might want to wait and add the PI3K inhibitor after you progress from firstline AI treatment, and a greater fraction of the cells will have developed the PI3K mutation and maybe get a more simultaneously response to the PI3K drug. It's not clear whether that idea will even be tested in clinical trials, but nevertheless it could be a good idea to wait and use it on resistant cells...

zarovka

Cure-ious - There is a lot of strategy to the sequencing of treatment. That's a brilliant observation. Putting that in my notes. I was actually thinking that I might want to add a PI3K inhibitor as soon as they came out, but it makes sense to hold it for either the second or third line, depending on how you want to move through the hormonals. Not planning to progress, of course, but it is interesting to consider ;-)

Mazie - I think this is the trial you are on. Very complicated structure. Should be of interest to anyone considering faslodex as a second line treatment or exemestane/everolimus as a third line treatment. They even have a herceptin line of treatment.

https://clinicaltrials.gov/ct2/show/NCT02057133?term=LY3023414+abemaciclib&rank=1

zarovka

Mazie - It sounds like one of the requirements for the trial is that you cannot have received systemic chemo for metastatic disease. IOW this has to be your first line treatment after being diagnosed as metastatic. Is that correct?

I like the trial alot, but that would exclude me, and a lot of people on this forum. It also means you must use it as a first line treatment, which may not be the best strategy, as Cure-ious points out.

>Z<