Therapeutic efficacy of Abemaciclib

1. Early Breast Cancer

VERZENIO in Combination with Standard Endocrine Therapy (monarchE)

Patient Population:

Adult women and men with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, node-positive early breast cancer at high risk of recurrence.

Study Design:

monarchE is a randomized, open-label, two-cohort, multicenter study. Patients must have HR-positive, HER2-negative early breast cancer with involvement of at least one axillary lymph node.

To be enrolled in Cohort 1, patients must meet one of the following criteria: ≥4 positive axillary lymph nodes, or 1-3 positive axillary lymph nodes with at least one of the following: tumor grade 3, tumor size ≥5 cm, or Ki-67 index ≥20% (central laboratory testing).

Patients enrolled in Cohort 2 do not meet the eligibility criteria for Cohort 1. To be enrolled in Cohort 2, patients must have 1-3 positive axillary lymph nodes and a Ki-67 score ≥20%.

Patients were randomly assigned to receive 2 years of VERZENIO plus physician’s choice of standard endocrine therapy or standard endocrine therapy alone. After completion of the study treatment period, standard adjuvant endocrine therapy continued for at least 5 years if medically appropriate.

Primary Efficacy Outcome Measure:

Invasive Disease-Free Survival (IDFS). Defined as the time from randomization to the first occurrence of any of the following events: ipsilateral invasive breast tumor recurrence, regional invasive breast cancer recurrence, distant recurrence, contralateral invasive breast cancer, second primary non-breast invasive cancer, or death from any cause. Overall Survival (OS) is an additional outcome measure.

Efficacy Results:

A statistically significant difference in IDFS was observed in the intent-to-treat population, primarily attributed to patients treated in Cohort 1. While OS data for Cohort 2 remain immature, more deaths were observed in patients receiving VERZENIO plus standard endocrine therapy (10/253 vs. 5/264).

Patient Characteristics:

Of the 5,637 randomized patients, 5,120 (91%) were randomized in Cohort 1. The median age of patients was 51 years, 99% were female, 70% were White, 24% were Asian, 1.7% were Black or African American, 2.1% were American Indian or Alaska Native, and 0.1% were Native Hawaiian or Other Pacific Islander. Forty-three percent of patients were premenopausal. Most patients had received prior chemotherapy (37% neoadjuvant, 59% adjuvant) and prior radiotherapy (96%). Sixty-five percent of patients had 4 or more positive lymph nodes, of whom 22% had ≥10 positive lymph nodes, 41% had grade 3 tumors, and 24% had pathological tumor size ≥50 mm. Most patients (99%) had estrogen receptor-positive disease, and 87% had progesterone receptor-positive disease. Initial endocrine therapies received by patients included letrozole (39%), tamoxifen (31%), anastrozole (22%), or exemestane (8%).

Efficacy Results in Cohort 1:

Invasive Disease-Free Survival (IDFS): 317 patients (12%) in the VERZENIO plus endocrine therapy group and 474 patients (18%) in the endocrine therapy alone group experienced events. The hazard ratio was 0.65. IDFS rate at 48 months: 85.5% in the VERZENIO combination group vs. 78.6% in the endocrine therapy alone group.

2. Advanced or Metastatic Breast Cancer

VERZENIO in Combination with Aromatase Inhibitors (Anastrozole or Letrozole) (MONARCH3)

Patient Population:

Postmenopausal women with HR-positive, HER2-negative advanced or metastatic breast cancer who have not received systemic therapy in this disease setting.

Study Design:

MONARCH3 is a randomized, double-blind, placebo-controlled, multicenter study evaluating VERZENIO in combination with a non-steroidal aromatase inhibitor as initial endocrine-based therapy in postmenopausal women. A total of 493 patients were randomly assigned to receive 150 mg VERZENIO or placebo orally twice daily, plus physician’s choice of letrozole (80% of patients) or anastrozole (20% of patients).

Patient Characteristics:

The median age of patients was 63 years, and most were White (58%) or Asian (30%). A total of 51% had received prior systemic therapy, 39% had received prior chemotherapy, 53% had visceral disease, and 22% had bone-only disease.

Efficacy Results:

Progression-Free Survival (PFS): Median PFS was 28.2 months in the VERZENIO combination group vs. 14.8 months in the placebo combination group. The hazard ratio was 0.54.

Overall Survival (OS): Median OS was 66.8 months in the VERZENIO combination group vs. 53.7 months in the placebo combination group. The hazard ratio was 0.80.

Objective Response Rate (ORR): Among patients with measurable disease, ORR was 55% in the VERZENIO combination group vs. 40% in the placebo combination group.

VERZENIO in Combination with Fulvestrant (MONARCH2)

Patient Population:

Women with HR-positive, HER2-negative advanced or metastatic breast cancer whose disease progressed during or after prior adjuvant or metastatic endocrine therapy and who have not received chemotherapy in the metastatic setting.

Study Design:

MONARCH2 is a randomized, placebo-controlled, multicenter study. A total of 669 patients were randomly assigned to receive VERZENIO or placebo orally twice daily, plus 500 mg fulvestrant intramuscularly on Days 1 and 15 of Cycle 1, followed by Day 1 of each subsequent cycle. Premenopausal/perimenopausal women were enrolled and received the gonadotropin-releasing hormone (GnRH) agonist goserelin for at least 4 weeks prior to the start of MONARCH2 and throughout the study period.

Patient Characteristics:

The median age of patients was 60 years, and 37% of patients were older than 65 years. Most were White (56%), and 99% of patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Twenty percent of patients had de novo metastatic disease, 27% had bone-only disease, and 56% had visceral disease. Twenty-five percent of patients had primary endocrine resistance. Seventeen percent of patients were premenopausal or perimenopausal.

Efficacy Results:

Progression-Free Survival (PFS): Median PFS was 16.4 months in the VERZENIO combination group vs. 9.3 months in the placebo combination group. The hazard ratio was 0.55.

Overall Survival (OS): Median OS was 46.7 months in the VERZENIO combination group vs. 37.3 months in the placebo combination group. The hazard ratio was 0.76.

Objective Response Rate (ORR): Among patients with measurable disease, ORR was 48% in the VERZENIO combination group vs. 21% in the placebo combination group.

VERZENIO as Monotherapy for Metastatic Breast Cancer (MONARCH1)

Patient Population:

Patients with HR-positive, HER2-negative breast cancer who have received prior endocrine therapy and 1-2 chemotherapy regimens in the metastatic setting.

Study Design:

MONARCH1 is a single-arm, open-label, multicenter study enrolling 132 women with measurable HR-positive, HER2-negative metastatic breast cancer whose disease progressed during or after endocrine therapy, who have received taxane therapy in any setting, and who have received 1 or 2 prior chemotherapy regimens in the metastatic setting. All patients received 200 mg VERZENIO orally twice daily, administered continuously until disease progression or unmanageable toxicity.

Patient Characteristics:

The median age of patients was 58 years, and most were White (85%). Patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 (55%) or 1 (45%). The median duration of metastatic disease was 27.6 months. Ninety percent of patients had visceral metastases, and 51% had 3 or more metastatic sites. Fifty-one percent of patients had received first-line chemotherapy in the metastatic setting. Sixty-nine percent of patients had received a taxane-based regimen in the metastatic setting, and 55% had received capecitabine in the metastatic setting.