This was an interview with Dr. Sara Tolaney who attended a recent conference:
" And so, at ESMO, they presented data from the second interim analysis of overall survival from MONARCH 3. And while there was not a statistically significant benefit in overall survival, there was a clinically meaningful trend in overall survival with a 12.8-month difference between the two arms, favoring abemaciclib. And when you also looked at outcomes amongst patients with visceral metastases, there was about a 16-month difference in overall survival, again favoring abemaciclib."
"So, I think, again, while this study did not reach statistical significance, it was at the time of a second interim analysis, and so, there is likely to be a subsequent overall survival analysis that will be presented in 2023, and hopefully, that one will technically reach statistical significance. But at this time, I think these data are clinically meaningful and I think allow us to think about having choice of CDK4/6 inhibition when selecting one to be given in combination with endocrine therapy in the first-line setting."
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Hazelgreen
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Forgive me for doing this out loud, but I am trying to think through what this means. This study looked at nonsteroidal aromatase inhibitors + abemaciclib. That would be Letrozole or Anastrozole (not Tamoxifen - steroidal) + Verzenio. I think (I should look it up) one arm was the AI alone and the other was AI + abemaciclib.
If it there was no statistically significant difference between the two groups/arms, that means the difference was not reliable, and it could have occurred by chance. I understand that something can be statistically significant but not clinically (effect size too small to matter much) but I don't understand statistically ns but clinically significant. Unless the sample size was too small and the test did not have enough power, but I doubt that. Or the probability is .09 and we wouldn't call that significant but it is trending that way.
Then the overall survival of 12.8 months longer in the abemaciclib group (which was ns) but 16 month advantage among those with visceral mets. (Visceral means into organs, right? Generally has a lower survival rate.) That sounds paradoxical, as though those with visceral disease in the abemaciclib arm lived longer than the others. The only way to make sense of that, given the overall 13 month advantage, is that they compared those with visceral disease in both arms, and those in the AI-only arm had shorter average survival than the group as a whole, so the advantage to those in the abemaciclib arm was relatively more pronounced.
It never sounds as good when I break it down. Still, since I am on anastrozole and abemaciclib, it is good news. I am not sure if I have visceral mets -- or had them, gone now. I had mets in my pleura. My oncologist calls that "lung," but it is not really. When I press her, she says it is outside the lungs. Yet it is written in my record as mbc in my lungs. I guess it doesn't matter because we don't follow the statistics in our paths exactly, what happens to each of us is what happens, but I like to deny that I have visceral disease and therefore might have more time.🙂
This was a review of a paper presented at a conference. It has yet to be published in a journal. Once it is published, we'll be able to read the details on Pubmed.
According to Google, the difference between clinical and statistical significance is, "In medical terms, clinical significance (also known as practical significance) is assigned to a result where a course of treatment has had genuine and quantifiable effects. Broadly speaking, statistical significance is assigned to a result when an event is found to be unlikely to have occurred by chance." In most cases, statistical significance is only reached when the likelihood that the results occurred by chance is less than 5%. When the study is published, you and I will learn what the actual percentage was. It could have been 9%, clearly trending in the right direction...
It is indeed surprising that those with visceral mets lasted longer on average. I think your reasoning ("those in the AI-only arm had shorter average survival than the group as a whole,") makes eminent sense (as does other possibilities such as the early demise of a few non-visceral patients pulled that average down more than expected)! More extreme outliers can pull any average down. It really is helpful to read the details in specific studies.
My guess is that Eli Lily is funding much longer research expecting that ultimately the results on overall survival with Verzenio will be significant, and will help sales. You and I will both be interested to read findings about averages. In the meantime, I agree that each of our cases is unique, and "what happens to each of us is what happens".
I think you are right. Previous lines of treatment do make a difference in current responses. The reason for this (which likely also varies among individuals) is another possible line of research if we could ever persuade medical researchers to focus on individual differences in treatment responses.
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Good News re: CDK4/6 Inhibitors & Overall Survival 
