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Abemaciclib Data Show Benefit Across Breast Cancer Subgroups

Gina Columbus
Published: Thursday, Jul 05, 2018

Maura Dickler, MD

Maura Dickler, MD

A handful of abstracts involving the CDK4/6 inhibitor abemaciclib (Verzenio) presented at the 2018 ASCO Annual Meeting demonstrated the agent’s efficacy and impact on quality of life (QOL) across subpopulations of patients with hormone receptor (HR)–positive, HER2-negative breast cancer.

The FDA approved abemaciclib in February 2018 as a frontline therapy in combination with a nonsteroidal aromatase inhibitor for postmenopausal patients with HR-positive, HER2-negative breast cancer. The approval was based on data from the phase III MONARCH 3 trial, which also showed that the CDK4/6 inhibitor improved outcomes in patients with concerning clinical characteristics, including visceral metastases.1

Abemaciclib was initially approved in September 2017 for use in combination with fulvestrant (Faslodex) to treat patients with advanced disease that has progressed on endocrine therapy, as well as for single-agent use for patients with HR+/HER2- breast cancer with metastatic disease who have previously received endocrine therapy and chemotherapy.

A subgroup analysis of the MONARCH 2 study presented at the 2018 ASCO Annual Meeting showed that the combination of abemaciclib and fulvestrant plus a GnRH agonist was found to improve progression-free survival (PFS) and overall response rates (ORRs) in both pre- and perimenopausal women with HR-positive, HER2-negative advanced breast cancer.2 The median PFS was not reached for the abemaciclib/fulvestrant arm and was 10.5 months for the placebo with fulvestrant arm (HR, 0.446; 95% CI, 0.264-0.754; P = .002). In those with measurable disease, the ORR was higher in the abemaciclib arm versus placebo at 60.8% versus 28.6%.

A second analysis from the MONARCH 2 trial presented at the 2018 ASCO Annual Meeting, evaluated the health-related QOL in those who received abemaciclib plus fulvestrant following progression on endocrine therapy.3 Findings showed that while there were higher rates of gastrointestinal-related adverse events in early visits, there was no statistically significant decline in patient-reported global health or symptoms versus fulvestrant/placebo.

Moreover, an analysis of dose-reduction strategies in the MONARCH 1, MONARCH 2, and MONARCH 3 studies demonstrated that there was no difference in PFS for patients who required dose reductions with abemaciclib due to diarrhea or neutropenia versus those who did not.4 Additionally, efficacy was still observed in patients regardless of whether they experienced events of neutropenia or diarrhea early in treatment.

Overall, CDK4/6 inhibitors have created “a tremendous advance in the first- and second-line settings,” said Maura Dickler, MD, adding, “we have not seen improvements in PFS as we have with this class of drugs.”

In an interview with OncLive during ASCO, Dickler, vice president, Late Phase Oncology Development, Eli Lilly and Company expanded on the findings with abemaciclib presented at this year’s meeting and what some of the next steps are for the CDK4/6 inhibitor.

OncLive: We saw interesting data presented with abemaciclib at the 2018 ASCO Annual Meeting. Can you discuss the findings with pre- and perimenopausal women?

Dickler: Dr Patrick Neven presented the data for abemaciclib in a pre- and perimenopausal group of women who participated in the MONARCH 2 trial. MONARCH 2 was a large, randomized phase III study where about 114 women were pre- and perimenopausal. But, everyone was given an GnRH agonist to make sure they were in menopause while they were receiving abemaciclib on study.

For that subgroup of 114 women, what this presentation nicely demonstrated was that there was a clear benefit of abemaciclib when added to fulvestrant in all patient subgroups, including the pre- and perimenopausal women included on this study. Therefore, it is reassuring to see that these data add to the evidence showing that abemaciclib specifically works in all subgroups of women. The MONARCH 2 data really are strong data showing that abemaciclib adds to the benefit of fulvestrant in this population of patients.

Have any differences between the 3 FDA-approved CDK4/6 inhibitors been identified?

There are no head-to-head studies of the CDK4/6 inhibitors, so we really can’t make inferences about the differences between the agents or the comparative effectiveness of each drug. We can really only comment on the trials that have been reported to date.

There really aren’t data to help guide the [decision] on which [drug] you would use. There are first-line trials with all 3 agents [as well as] second-line trials. Looking at each study, there are benefits in the first- and second-line settings with hazard ratios that are very similar. But, you can’t compare trials.

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