CDK4/6 Inhibitors in Breast Cancer: New Populations, Different Settings

At the American Society of Clinical Oncology (ASCO) annual meeting, a poster discussion session on metastatic breast cancer entitled “CDK4/6 Inhibitors: New Populations, Different Settings” was presented by Maryam Lustberg, MD, MPH, the chief of breast oncology at the Yale Cancer Center in New Haven, Connecticut. She discussed the results from three posters — the LEONARDA-1 study, the PALOMAGE program, and the AURORA Molecular Screening Initiative.

In this exclusive MedPage Today video, Lustberg reviews her presentation and discusses the three poster abstracts.

Following is a transcript of her remarks:

So, I was a discussant on ASCO 2023’s metastatic poster abstracts. And the three abstracts that I reviewed included the LEONARDA-1 study, which investigated the use of a new CDK4/6 inhibitor by the name of lerociclib in patients with metastatic breast cancer who had progressed on one line of prior endocrine therapy. And similar to other CDK4/6 inhibitor studies, the addition of the CDK4/6 inhibitor significantly prolonged progression-free survival. The overall survival data are not yet mature. However, it had [an] acceptable toxicity profile similar to other CDK4/6 inhibitors. Patients did experience some degree of neutropenia, diarrhea, and fatigue. No other new safety signals were identified. And so, the data are continuing to mature.

Where this agent fits in the current arsenal of three approved CDK4/6 inhibitors, that really remains to be determined. In my discussion, I raised the possibility that perhaps as we develop new CDK4/6 inhibitors, perhaps the competition among having more agents available may help decrease costs and increase access around the globe, where we know that there are many underserved countries who may not have as wide an access to these agents.

The second poster that I discussed was the PALOMAGE study, which builds on continued recognition that patients who are older can still benefit from targeted therapies. In this study, patients with metastatic breast cancer who were older than 70 years old received palbociclib [Ibrance]. And what the study showed is that there was a range of expected challenges that these patients experienced receiving this drug. Some required dose reductions and dose modifications. However, in general, really what determined if a patient did well or did not do as well with this therapy was really initial performance status and functional status.

So really, the take-home message is to not specifically look at the age parameter itself, but really treat the whole patient and really look at what their functional capacities are. And also not be afraid to do dose modifications when indicated to make our therapies more tolerable.

The third abstract that I discussed was a molecular study, results from the international AURORA study, which had been including patients with both metastatic tissue and primary tumor tissue. And the question that was presented was, what were the molecular care characteristics of patients with metastatic breast cancer who were receiving first-line CDK4/6 inhibitor? The majority of these patients were receiving palbociclib in combination with either an aromatase inhibitor or a SERD [selective estrogen receptor degrader]. And the question was, were there certain predictive biomarkers of better or worse outcomes?

The following findings were discussed, including that there was no difference between invasive and lobular cancers. There was no difference in outcomes in terms of [PIK3CA] status. However, patients who had an ESR1 mutation had worse outcomes overall, in terms of progression-free survival. And this was regardless of what type of endocrine therapy they received, and they were less likely to benefit from CDK4/6 inhibitor therapy.

These are all still very preliminary findings and in no way are the authors or myself suggesting that we should use ESR1 mutational status to restrict CDK4/6 inhibitor use. But I think it does raise some questions in terms of how we can better target patients with ESR1 mutations and help them have more prolonged outcomes from our various targeted therapies.

With emerging options in SERD therapy and additional combinational approaches, I think this is what future studies will be further investigating.