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CKD4/6 Inhibitor in First-Line Treatment for mBC: What Comes Next?

<ѻýҕl class="mpt-content-deck">— Evidence isn't great to inform a sequencing choice, says Megan Kruse, MD
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At the virtual San Antonio Breast Cancer Symposium, researchers presented results from research on real-world sequential and non-sequential use of CDK4/6 inhibitors in metastatic, hormone receptor-positive, HER2-negative breast cancer patients.

In this exclusive ѻýҕl video, study author , of the Cleveland Clinic, discusses the results and clinical impact of her study.

Following is a transcript of her remarks:

This presentation was a look at real-world data from patients who were treated with endocrine therapy and a CDK4/6 inhibitor with at least one of those treatment lines including abemaciclib [Verzenio]. And the idea of this project was really to analyze how CDK4/6 inhibitors are used either sequentially or non-sequentially for treatment of metastatic hormone receptor-positive, HER2-negative breast cancer patients.

The cohort of patients that was assessed was nearly 700 patients that were treated in largely community settings in the United States, about 80% community settings and 20% academic settings. And again, they were all patients who received a various number of treatments for metastatic hormone receptor-positive HER2-negative breast cancer. And in these patients, there was a lot of treatment heterogeneity. So we tried to break them into groups to better analyze their outcomes based on the treatments that they received.

And so the way that those groups were designed, we had four total groups and that would be patients who received an endocrine therapy with a CDK4/6 inhibitor in the first line treatment for their metastatic breast cancer, followed by another CDK4/6 inhibitor containing therapy in the second line. So that was first to second line sequential treatment. Then there was another group of patients, still first to second line, but they had CDK4/6 inhibitor in the first line, and then non-sequential treatment in the second line, meaning that their treatment was anything other than containing a CDK4/6 inhibitor. And then for groups three and four, we replicated that. For patients going from the second line to the third line, again with sequential CDK4/6 inhibitor treatment, or essentially without CDK4/6 inhibitor in the next line of therapy.

And what we found is for patients that had sensitivity to the endocrine therapy and CDK4/6 inhibitor in the first line, they tended to also have good response in the second line, measured by prolonged progression-free survival. For the patients who had more suboptimal progression-free survival on that endocrine therapy, CDK4/6 inhibitor, and whether it was their first or second line, but the first time they were exposed to this combination therapy -- when they went to non-sequential therapy, they actually had an inferior progression-free survival numerically.

And so what I think this is telling us, because even though the groups were matched very, very well for all their clinical related characteristics, tumor related characteristics, it probably means there's something biologically about the tumors for those patients who did not receive sequential CDK4/6 inhibitor use and whether that was something that was picked up by providers, where they didn't think that that sequential use was appropriate, or if there was some sort of tumor biology difference that we cannot capture, say a genomic or molecular difference.

The other thing that we didn't capture very well in the database was visceral crisis. And so I do wonder to myself if these were patients who were having tumor organ function impact, and providers felt like switching to a different mode of therapy was appropriate. And in fact, in those non-sequential patients, most of the patients actually received chemotherapy.

So certainly hypothesis-generating for what is different between the groups where it was felt that sequential therapy was appropriate versus not, and gives us opportunities to dig into this data further in the future.

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    Greg Laub is the Senior Director of Video and currently leads the video and podcast production teams.