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The MAINTAIN trail confirmed the benefit of switching endocrine therapy and continuing CDK4/6 therapy in patients with HR+/HER2- breast cancer whose disease progressed on the two treatments.

Kevin Kalinsky, MD, of Winship Cancer Institute of Emory University in Atlanta, and colleagues reported significantly improved progression-free survival (PFS) in patients who received a change in endocrine therapy and continuation of CDK4/6 compared with those who received endocrine therapy alone (5.29 vs 2.76 months, HR 0.57, P=0.006).

As the researchers explained in the most of the 119 participants in MAINTAIN (86%) had previously received palbociclib. The rest has previously received ribociclib. However, all patients in the trial received ribociclib as the continuation of their CDK4/6 therapy.

"The introduction of any new therapy brings a question of what to do at the time of progression," the researchers wrote. "The MAINTAIN trial informs treatment decisions for patients progressing on initial hormone therapy with palbociclib. Additional studies are needed to compare this approach with other second-line hormone therapy options such as phosphatidylinositol 3-kinase- and mammalian target of rapamycin-inhibitor based treatments."

In the following interview, Kalinsky, who is Louisa and Rand Glenn Family Chair in Breast Cancer Research and Director of Breast Medical Oncology, discussed the details of the trial and ongoing research.

What do you see as the main clinical implication of this study?

Kalinsky: I think there are two implications. First, single-agent hormonal therapy after progression on a CDK4/6 inhibitor has really limited activity. That has been seen across various studies, including the MAINTAIN and EMERALD trials. That is something that has been consistent, and we should think about when we are treating our patient. With the concerns about endocrine therapy that we have now, there is limited activity with single-agent fulvestrant after CDK4/6 inhibitor progression.

Also, there is within NCCN [National Comprehensive Cancer Network] guidelines a notation about the MAINTAIN study that mentions there are data supporting ribociclib after progression on CDK4/6 inhibition. It is important to mention that this was a randomized phase II trial. There are other studies that we waiting for results on, including postMONARCH.

Did you find anything notable in any of your subgroup analyses?

Kalinsky: There was a subgroup of patients who had ribociclib after ribociclib. The majority had ribociclib after palbociclib. The subgroup of patients who had ribociclib after ribociclib had a similar hazard ratio as ribociclib after palbociclib.

One of the questions is, do you keep the same CDK4/6 inhibitor? And our results are completely hypothesis-generating, and that confidence interval is quite wide with such small numbers, but there is a subgroup of patients for whom we have data.

We also looked at mutation status, and we saw that patients who had ESR1 mutations did not benefit from the addition of ribociclib. And that could just be small numbers. It could be that ESR1 mutations are associated with other resistance mechanisms that we are not accounting for. But it is important that in other studies, in PALMIRA and in PACE, which were randomized studies of palbociclib after palbociclib, they did not have that same finding. It will be important in postMONARCH, the largest of the randomized trials, to see what that biomarker looks like.

Did you find any new safety signals?

Kalinsky: No. The patients in this trial would have already tolerated a prior CDK4/6 inhibitor, but we did not see any new safety signals.

Is there anything else you would like to make sure oncologists understand about this study or this topic?

Kalinsky: The landscape is evolving. We may see the approval of capivasertib and everolimus, but CDK4/6 inhibitors are targeted drugs with which we are very familiar, and if there is some activity giving a CDK4/6 after CDK4/6, this could inform practice, given that these are drugs with known toxicity profiles.

Do you have any other research planned or ongoing in this area?

Kalinsky: There is a randomized phase III trial that has completed accrual which we will hopefully see results on. It's the study, which is comparing fulvestrant with abemaciclib vs fulvestrant alone in patients who have tumors that could have progressed on any CDK4/6 inhibitor, including progression on adjuvant CDK4/6.

Read the study here and expert commentary about it here.