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Analysis Shows Benefit of Abemaciclib in Women With Worse Prognosis

Allison Inserro
A recent study of abemaciclib, a cyclindependent kinase 4 and 6 inhibitor for metastatic breast cancer, found that it helped all women with hormone receptor–positive, human epidermal growth factor receptor 2–negative disease, and that it was particularly beneficial in women with a worse prognosis.
A recent study of abemaciclib, a cyclindependent kinase 4 and 6 inhibitor for metastatic breast cancer, found that it helped all women with hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2-) disease, and that it was particularly beneficial in women with a worse prognosis.

The results came from exploratory subgroup analyses of the MONARCH 2 and MONARCH 3 trials. MONARCH 2 and 3 enrolled women with HR+, HER2- advanced breast cancer.

In MONARCH 2, patients whose disease had progressed while receiving endocrine therapy (ET) were given fulvestrant plus abemaciclib or placebo.

In MONARCH 3, patients received a nonsteroidal aromatase inhibitor plus abemaciclib or placebo as initial therapy for advanced disease. A combined analysis of the 2 studies was performed to determine significant prognostic factors.

In a statement, Eli Lilly, which sells abemaciclib under the name Verzenio, said the exploratory post hoc analyses pooled data from over 1000 patients using a 2-step approach.

First, the identification of independent prognostic variables, regardless of treatment assignment, were derived from the entire population. Then, the descriptions of the treatment effect of endocrine monotherapy compared with ET plus Verzenio were examined in each of the identified prognostic subgroups within the respective studies.

Efficacy results—progression-free survival (PFS) and overall response rate (ORR) in patients with measurable disease—were examined for patient subgroups corresponding to each significant prognostic factor.

These clinical factors were found 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
  • Time from diagnosis to recurrence
Prognosis was poorer in patients with liver metastases, progesterone receptor-negative tumors, high grade tumors, or short TFI (less than 36 months).

Benefit (PFS hazard ratio, ORR increase) from abemaciclib was observed in all patient subgroups. But 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 more than 20 months. These analyses identified prognostic factors and demonstrated that patients with poor prognostic factors derived the largest benefit from the addition of abemaciclib.

Patients whose cancer spread to the liver had the shortest PFS using endocrine monotherapy, with a median PFS of 7.2 months in MONARCH 3 and 3.1 months in MONARCH 2.

Shorter PFS was also observed in the control arm in patients with either progesterone receptor (PgR)–negative or high-grade tumors. In contrast, the median PFS for patients treated with endocrine monotherapy was substantially longer for patients with an Eastern Cooperative Oncology Group performance status of 0 (MONARCH 3, 15.7 months; MONARCH 2, 10.3 months) or bone-only disease (MONARCH 3, 27.5 months; MONARCH 2, 16.6 months).

“Not all patients with HR+, HER2- metastatic breast cancer are the same. Each patient presents with unique patterns of clinical factors—with some patients having particularly concerning clinical characteristics that can signal a poor prognosis to oncologists. Therefore, treatment decisions must be tailored to each patient’s individual presentation,” said Joyce O’Shaughnessy, MD, Celebrating Women Chair in Breast Cancer Research and chair, Breast Cancer Research Program, Baylor University Medical Center, Texas Oncology and US Oncology, Dallas, Texas. “Understanding the prognostic value of certain clinical factors and how patients with or without these factors may respond to the addition of Verzenio can help us as we seek to individualize treatment decisions.”

“These data further reinforce that we may be able to distinguish potential benefit of CDK4 & 6 inhibitor treatment in certain groups of patients,” said Angelo Di Leo, MD, PhD, medical oncologist, Sandro Pitigliani Medical Oncology Department, Hospital of Prato, Istituto Toscano Tumori, Prato, Italy. “By pooling data across the MONARCH 2 and MONARCH 3 studies, we were able to maximize the power to detect prognostic factors, helping to lay the foundation for optimizing treatment for our patients.”

The company said that patients with cancer that spread to the liver, PgR-negative tumors, or high tumor grade cancers received a substantial benefit with Verzenio, with a greater than 30% difference in response rates.

In addition, in MONARCH 3, the exploratory subpopulation treatment effect pattern plot analysis of TFI showed that those whose cancer returned quickly after the conclusion of adjuvant ET saw larger benefit from the addition of Verzenio compared with ET alone.


Di Leo A, O’Shaughnessy J, GW Sledge Jr, et al. Prognostic characteristics in hormone receptor-positive advanced breast cancer and characterization of abemaciclib efficacy [published online December 18, 2018]. NPJ Breast Cancer. doi: 10.1038/s41523-018-0094-2.

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