Abstract
CDK4 & 6 inhibitors have enhanced the effectiveness of endocrine therapy (ET) in patients with advanced breast cancer (ABC). This paper presents exploratory analyses examining patient and disease characteristics that may inform in whom and when abemaciclib should be initiated. MONARCH 2 and 3 enrolled women with HR+, HER2- ABC. In MONARCH 2, patients whose disease had progressed while receiving ET were administered fulvestrant+abemaciclib/placebo. In MONARCH 3, patients received a nonsteroidal aromatase inhibitor+abemaciclib/placebo as initial therapy for advanced disease. A combined analysis of the two studies was performed to determine significant prognostic factors. Efficacy results (PFS and ORR in patients with measurable disease) were examined for patient subgroups corresponding to each significant prognostic factor. Analysis of clinical factors confirmed the following to have prognostic value: bone-only disease, liver metastases, tumor grade, progesterone receptor status, performance status, treatment-free interval (TFI) from the end of adjuvant ET, and time from diagnosis to recurrence. Prognosis was poorer in patients with liver metastases, progesterone receptor-negative tumors, high grade tumors, or short TFI (<36 months). Benefit (PFS hazard ratio, ORR increase) from abemaciclib was observed in all patient subgroups. Patients with indicators of poor prognosis had the largest benefit from the addition of abemaciclib. However, in MONARCH 3, for patients with certain good prognostic factors (TFI ≥ 36 months, bone-only disease) ET achieved a median PFS of >20 months. These analyses identified prognostic factors and demonstrated that patients with poor prognostic factors derived the largest benefit from the addition of abemaciclib.
Highlights
Over 70% of metastatic breast cancers are hormone receptorpositive (HR+) and are treated with sequential endocrine-based therapies.[1,2,3,4] Endocrine therapies (ETs) may initially be efficacious and well-tolerated in a substantial proportion of patients with HR+ breast cancer
This subgroup analysis of the MONARCH 2 and 3 trials evaluates and determines the independent prognostic effects of a large number of pathological and clinical characteristics that can inform the prognosis of patients treated with contemporary endocrinebased therapy. This analysis used a data set derived from over 1000 patients who participated in the MONARCH 2 and 3 Phase III studies
Reported subgroup analyses of studies combining CDK4 & 6 inhibitors with ET have concluded that all subgroups benefit from the addition of CDK4 & 6 inhibitors.[7,8,9,10,22]
Summary
Over 70% of metastatic breast cancers are hormone receptorpositive (HR+) and are treated with sequential endocrine-based therapies.[1,2,3,4] Endocrine therapies (ETs) may initially be efficacious and well-tolerated in a substantial proportion of patients with HR+ breast cancer. Given the complexity of these treatments, the identification of patient and tumor characteristics that can help inform when to use CDK4 & 6 inhibitors in the treatment paradigm and in which patients is a subject of considerable interest.[13,20,21] CDK4 & 6 inhibitor trials published to date have demonstrated treatment benefit for the addition of a CDK4 & 6 inhibitor to ET across all patient subgroups.[7,8,9,10,12,22] The present analyses of abemaciclib aim to determine independently prognostic subgroups, characterize the benefit of the addition of abemaciclib to endocrine therapy in these subgroups, and determine those which derived the largest benefit from abemaciclib and those for which endocrine monotherapy may be an appropriate initial treatment This approach may inform tailoring of treatment choices to individual patients. These analyses use data from two Phase III studies in patients with HR+, HER2− ABC in which abemaciclib plus ET significantly
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