Home Breast Cancer Significant Survival Benefit Found with Ribociclib in Metastatic Breast Cancer

Significant Survival Benefit Found with Ribociclib in Metastatic Breast Cancer

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Intrinsic tumor subtype was found to be associated with prognosis in patients with hormone receptor–positive, HER2-negative advance breast cancer who received the CDK4/6 inhibitor ribociclib, according to data presented at the virtual 2020 San Antonio Breast Cancer Symposium. Only patients with basal-like subtype did not derive statistically significant benefit from ribociclib versus placebo.

In this exclusive MedPage Today video, study author Aleix Prat, MD, of the Hospital Clínic de Barcelona, discusses the potential reasons for such impressive results with luminal A, luminal B and HER2-enrich, but not the basil-like subtype, as well as how to best classify the intrinsic subtypes.

Following is a transcript of his remarks:

The HER2-enrich been shown both in early disease in neoadjuvant studies, looking at looking at endocrine therapy, and also in the metastatic setting, that it has a very poor outcome with endocrine therapy only. We confirmed this in the MONALEESA studies. However, we do see that ribociclib can definitely have activity there. On one hand, we would expect that maybe this group was less luminal and therefore would respond less to CDK-46 inhibitors. This is not the case. Our hypothesis, and again, this is a hypothesis, is that ribociclib could induce hormone sensitivity in this group that is not hormone sensitive to start with. So potentially there is a synergy between ribociclib inducing more endocrine sensitivity, and the addition of endocrine therapy in these patients. More work to be done.

On one hand, we did look at this profile of the basil-like subtype within the MONALEESA, of course, but we did compare the profiles of these basil-like compared to the classical triple negative basil-like disease. And this is in the future manuscript, and you will see that there are no major differences between the two. So definitely by gene expression analysis, this tumor looks just like a triple negative basil-like tumor. In my view, definitely this is a group of patients that are not benefiting from these drugs. It makes sense. These tumors usually have loss of RB. Whether this is ready for prime time, I don’t have the straight answer here. I do think that these patients progress very fast. The median PFS was 3.5 months. So I do think we need to look at additional strategies or different strategies in this really poor outcome group of patients.

I don’t think it’s going to be an easy task to use molecular chemistry to classify these intrinsic subtypes. I would like to point out that there are some features that might suggest that the tumor is not luminal, for example, low values of ER, or PR percentage low value. But again, we don’t have a specific cut point to tell, but in general, if a tumor has low ER/PR, these a tumor that is most likely is non luminal. And in particular it might be HER2-enrich. We have published previously a particular model called the NOLUS model, which integrate ER levels, PR levels, even Ki67, to try to identify the HER2-enriched and Basil-likes. And that model is published, is reported. However, this model, despite using that data will have a false positive and false negative rate of more than 30%. So it’s still far away to go. So I think we need to use gene expression data.

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    Greg Laub joined MedPage Today in 2005 as Production Manager and led the launch of the video department in 2007. He is currently responsible for the website’s video production. Follow

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