Kevin Kalinsky, MD, Winship Cancer Institute of Emory University, Atlanta, Georgia, shares primary outcomes from the phase 3 postMONARCH trial, evaluating abemaciclib plus fulvestrant for patients with HR-positive, HER2-negative advanced breast cancer who had progressed while on prior CDK4/6 inhibitors plus endocrine therapy.

This trial found a statistically significant improvement in progression-free survival with abemaciclib plus fulvestrant vs fulvestrant alone for this patient population. Dr Kalinsky concluded, “The take-home from this study is that there was a benefit of continuing a CDK4/6 inhibitor, in this case, abemaciclib, after progression on endocrine therapy and a CDK4/6 inhibitor, also switching to fulvestrant… This is a potential option for patients post-CDK4/6 inhibition and an aromatase inhibitor.”

Transcript:

Hi, I'm Kevin Klinsky. I am professor of medicine at Winship Cancer Institute at Emory University. And I'll be discussing the postMONARCH study. postMONARCH was an eagerly anticipated phase 3 trial. We'd seen other smaller phase 2 randomized trials of switching endocrine therapy and continuing with CDK4/6 inhibitor among patients who had tumors that had progressed previously on endocrine therapy and a CDK4/6 inhibitor.

This was a phase 3 trial of 368 patients where all patients received an aromatase inhibitor plus endocrine therapy, the vast majority in the metastatic setting. And then went on to be randomly assigned in a 1-to-1 fashion to fulvestrant plus abemaciclib versus fulvestrant plus placebo. The primary end point was investigator-assessed progression-free survival. This is a true second-line study. No patients had prior chemotherapy or any other therapy after progression on front-line treatment. And what we saw was there was statistically an improvement in progression-free survival per investigator assessment. The hazard ratio assumption was 0.7 and we saw a difference of 0.73.

We also talked about some of the pre-specified stratification factors, and we saw for some of the well-represented groups. Like those who were on their prior CDK4/6 inhibitor for at least 12 months, there was a ratio difference of 0.7, and that translated into a median PFS difference of about 1.5 months. And then if we look at those patients, for instance, who did not have visceral metastases, the hazard ratio was 0.5, and we saw a difference of about 5 to 6 months.

The other thing I just want to mention is that we did look at baseline circulating tumor DNA in about 85% to 90% of patients. We saw that there was no difference in terms of patients that had ESR1 mutations or PI3K pathway alterations. All patients seem to benefit with the addition of abemaciclib, and about 30 % of patients had neither.

The take-home from this study is that there was a benefit of continuing a CDK4/6 inhibitor, in this case abemaciclib, after progression on endocrine therapy and a CDK4/6 inhibitor, also switching to fulvestrant. We saw that the control arm did do better than what we've seen in other studies. And this may be because this is a true second line study, no patients had prior chemotherapy in the advanced setting.

The study did meet its primary end point as well as key secondary end points. There was a benefit regardless of the biomarker status. And there were no additional safety events that had happened. The discontinuation rate was relatively low at 6%. So this is a potential option for patients post-CDK4/6 inhibition and an aromatase inhibitor.

Thank you for your attention.

Source:

Kalinsky K, Bianchini G, Hamilton EP, et al. Abemaciclib plus fulvestrant vs fulvestrant alone for HR+, HER2- advanced breast cancer following progression on a prior CDK4/6 inhibitor plus endocrine therapy: Primary outcome of the phase 3 postMONARCH trial. Presented at 2024 ASCO Annual Meeting. May 31-June 4, 2024; Chicago, IL. Abstract #LBA1001