Ibrance/Abemaciclib

You probably already know this, but both are cdk4/6 inhibitors. They are different in the ratio of activity against cdk 4 vs 6. Abemaciclib is 16x more targeted to cdk 4 than either palbo or ribo. That leads to different side effects from the other two, more GI issues, less lowering of blood counts. As well, abemaciclib was the only one of the three to show some effectiveness on its own, not paired with an antihormonal agent. So that makes it different from the other two in an important respect. That said, I don't think anyone knows the answer as to whether abemaciclib is effective after failing on ibrance. Abemaciclib is so recently approved of that there would be little data outside the clinical trials, and I doubt they would have admitted anyone into a clinical trial of a cdk4/6 inhibitor that had previously failed on a cdk4/6 inhibitor, for fear of diminishing the chances of showing effectiveness. If you switch, I really hope it works for you and others. I think I would base my decision on how life threatening your current condition is. If it needs to be brought under control rapidly, then you are taking more of a chance with an unproven agent.

Here's a great article discussing the three drugs in that class:

https://www.medscape.com/viewarticle/883358#vp_1

On the topic of switching, I quote from the article:

"Given that the response to the CDK 4/6 inhibitors thus far seems to be a class-specific effect, one would imagine that once a patient experiences progression on one CDK 4/6 inhibitor, there would be no benefit of changing to another," they write. However, this has not been formally tested, they admit.

Approached for comment, Eric P. Winer, MD, director of the Breast Oncology Center at the Dana-Farber Cancer Institute, Boston, echoed a similar sentiment. "A critical piece of information that is relevant to clinical practice is to know whether CKD 4/6 inhibitors continue to work after initial progression," he told Medscape Medical News. Currently, in his own practice, Dr Winer does not continue to use the CDK 4/6 inhibitor when a patient initially progresses on a regimen containing the agent.

Lead author of the MONARCH 2 study, Dr Sledge, added a different slant: "Is the primary resistance that emerges with a CDK 4/6 inhibitor combination centered on CDK 4/6 inhibition or on the hormonal therapy component?" If the resistance is due to the hormonal component, one could possibly switch to another hormonal therapy and retain use of the initial CDK 4/6 inhibitor, he commented to Medscape Medical News.

He recounted that in the era before pertuzumab (Perjeta, Genentech/Roche), it was not uncommon to switch the chemotherapy when resistance emerged to a trastuzumab (Herceptin, Genentech/Roche)–chemotherapy combination.

end of quotes

Another thing to consider is whether as Dr. Sledge questions, whether its the cdk4/6 inhibitor that failed, or the anti hormonal therapy.

So, on that topic, although not applicable to you, as you failed on palbo plus fulvestrant, those who failed on palbo plus letrozole might consider this : from the National Cancer Institute: https://www.cancer.gov/types/breast/research/palbo...

Women who received palbociclib plus fulvestrant maintained their global quality of life, whereas quality of life declined in women who received a placebo plus fulvestrant.

At the time of this analysis, overall survival data were still immature.

Limitations

"The data are based on a prespecified interim analysis that showed the study had met the primary endpoint of improved progression-free survival," said Stan Lipkowitz, M.D., Ph.D., of NCI's Center for Cancer Research. "However, the median follow up was short—5.6 months—and the overall survival data were not mature.

"An issue not addressed is the use of palbociclib with fulvestrant after it has already been given as a first-line treatment in combination with letrozole. Based on the PALOMA1 data, and the accelerated FDA approval, many patients will likely receive palbociclib and letrozole in the first-line setting. Such patients who received palbociclib and letrozole would not have met the entry criteria for the PALOMA3 study," Dr. Lipkowitz added. "It will increasingly be the case that patients will have received palbociclib with letrozole as first-line therapy. Thus, this study does not provide guidance for whether patients who have had palbociclib and letrozole in the first-line will still benefit by adding palbociclib to fulvestrant in second-line treatment."

Comments

"At present palbociclib is not approved as a second-line treatment with fulvestrant," said Dr. Lipkowitz. "Fulvestrant is approved for second-line use alone. However, these data showing a two- to three-fold increase in progression-free survival are likely to lead many oncologists to use palbociclib plus fulvestrant as a second-line treatment of ER-positive, HER2-negative metastatic breast cancer in postmenopausal women. This will include patients who have gone through menopause or who have menopause induced by ovarian ablation."

Cure-ious, how does that compare with palbo/ibrance for area of most benefit?

Good question if Ibrance is less effective on bone mets than organ mets?, what I read was the clinical trial results for Abemaciclib, and they didn't mention how that compares to Palbo- I think it was striking because they said for patients with bone-only mets in their trial, the improvement was not even statistically significant, so Abemaciclib appears to be working best on the organ mets.

Ibrance (palbociclib) with Letrozole failed me (after about a year) but I was able to move onto Kisqali (ribociclib) with a new oral SERD (LSZ102) in a clinical trial.  My oncologist who is the principal research doctor for the study at Mass General (MGH) has already mentioned that if this protocol fails me that I still have the option to move on to Abemaciclib.  If I end up on Abemaciclib then I will have been on all 3 CDK 4/6 inhibitors (with different anti hormonals).  I think that since I'm part of the clinical trial I don't have to go through the same approval process with insurance but I'm not sure.  I guess I'll find out.  so it is interesting that having failed on one CDK 4/6 inhibitor doesn't necessarily mean you can't try the others.  

Hi All. Just jumping in to read your comments. Ibrance failed me and I can't take Kisquali because of an irregular heart rhythm so I am looking at Abemaciclib. The articles were very helpful Husband.

I wanted to take it cause Ibrance stopped working for me and my OC said it's another name for Ibrance . I am trying everything within my power to stay away from chemo

kisquali is the same as ibrance, mostly.

abemacilib is significantly different.

>Z<

LMWL - Praying for a great outcome. Please stop by with updates. It's very nice to be back on the same thread with you. I hope to chatting about your wife's continued strong response to this treatment for a long time.

>Z<

WorkingMom: sorry you are out of the trial. I was never qualified for that trial in October ,2017 because of prior medical history. However you did have a stable result for 16 months, congratulations! It looks like you still have a lot options in your treatments! Good luck on your next treatment

I have been treated in Start center since September 2010.. maybe we have crossed each other in the waiting room sometimes.