The Benefit of Abemaciclib in Prognostic Subgroups: An Exploratory Analysis of Combined Data from MONARCH 2 and 3

Conference Correspondent  - SABCS

Abemaciclib is an orally administered, selective inhibitor of CDK4/6 that is dosed on a twice-daily, continuous schedule. Abemaciclib has demonstrated clinical efficacy with a generally tolerable safety profile in patients with hormone receptor (HR)-positive, HER2-negative advanced breast cancer in combination with fulvestrant in MONARCH 2, and in combination with nonsteroidal aromatase inhibitors (NSAIs) in MONARCH 3.1,2 The analyses presented at SABCS 2017 were conducted to evaluate if patient and disease characteristics may better inform in whom and when abemaciclib should be initiated to define optimal treatment strategies.3

MONARCH 2 and 3 enrolled patients with HR-positive, HER2-negative advanced breast cancer. In MONARCH 2, patients whose disease had progressed while receiving endocrine therapy were treated with abemaciclib/placebo plus fulvestrant. In MONARCH 3, patients were treated with abemaciclib/placebo plus NSAIs as initial therapy for advanced disease. An exploratory pooled analysis of the 2 studies was performed to determine significant prognostic factors. Efficacy results (progression-free survival [PFS] and objective response rate [ORR] in patients with measurable disease) were examined for patient subgroups corresponding to each of the identified significant prognostic factors. Subpopulation Treatment Effect Pattern Plot (STEPP) methodology was performed to examine the association between treatment-free interval (TFI) following adjuvant endocrine therapy and outcomes of endocrine therapy alone or in combination with abemaciclib in MONARCH 3.

Analyses of clinical factors in more than 1000 patients confirmed the following to have prognostic value: bone-only disease, liver metastases, tumor grade, progesterone receptor (PgR) status, and Eastern Cooperative Oncology Group performance status. Prognosis was poor in patients with liver metastases, PgR-negative tumors, and high-grade tumors. While all subpopulations benefited from the addition of abemaciclib to endocrine therapy regardless of prognosis, a substantial benefit of abemaciclib was observed in poor-prognosis subgroups characterized by large increases in PFS (hazard ratio, 0.4-0.5) and ORR (>30%). In addition, STEPP analysis of TFI on a subset of the MONARCH 3 population showed that patients with the shortest TFI appeared to have a poorer prognosis and received more benefit from the addition of abemaciclib compared with patients with a longer TFI.

The authors concluded that this exploratory analysis has provided data that could help optimize treatment strategies by demonstrating that patients with HR-positive, HER2-negative breast cancer with poor prognostic factors may receive greater benefit from the addition of abemaciclib to endocrine therapy. Further data are needed to inform treatment strategies for patients with more favorable baseline prognostic factors, such as bone-only metastases and long TFI.

References
  1. Sledge GW Jr, et al. J Clin Oncol. 2017;35:2875-2884.
  2. Goetz MP, et al. J Clin Oncol. 2017;35:3638-3646.
  3. Goetz MP, et al. SABCS 2017. Abstract GS6-02.
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Last modified: April 27, 2020