Eli Lilly and Co.
Verzenio
28 x 50mg oral tablets per box
VERZENIO® is a kinase inhibitor.
Available in Tablets: 50 mg, 100 mg, 150 mg, and 200 mg provided as immediate-release oval white, beige, or yellow tablets indicated to be taken with or without food twice daily with a recommended and approved starting dose of 150mg for combination therapy or 200mg for monotherapy.
VERZENIO® is a kinase inhibitor indicated:
- in combination with endocrine therapy (tamoxifen or an aromatase inhibitor) for the adjuvant treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, node-positive, early breast cancer at high risk of recurrence. (, )
14.1 Early Breast CancerVERZENIO in Combination with Standard Endocrine Therapy (monarchE)Patients with HR-positive, HER2-negative, node-positive early breast cancer at high risk of recurrencemonarchE (NCT03155997) was a randomized (1:1), open-label, two cohort, multicenter study in adult women and men with HR-positive, HER2-negative, node-positive, resected, early breast cancer with clinical and pathological features consistent with a high risk of disease recurrence. To be enrolled, patients had to have HR-positive HER2-negative early breast cancer with tumor involvement in at least 1 axillary lymph node (pALN) and to be enrolled in cohort 1 had to have either:
- ≥4 pALN or
- 1-3 pALN and at least one of:
– tumor grade 3 or– tumor size ≥50 mm
Patients enrolled in cohort 2 could not have met the eligibility criteria for cohort 1. To be enrolled in cohort 2, patients had to have 1-3 pALN and Ki-67 score ≥20%. Breast tumor samples were tested at central sites using the Ki-67 IHC MIB-1 pharmDx (Dako Omnis) assay to establish if the Ki-67 score was ≥20%.
Patients were randomized to receive 2 years of VERZENIO plus physician's choice of standard endocrine therapy or standard endocrine therapy alone. Randomization to treatment was stratified by prior treatment (neoadjuvant chemotherapy versus adjuvant chemotherapy versus no chemotherapy); menopausal status (premenopausal versus postmenopausal); and region (North America/Europe versus Asia versus other). Men were stratified as postmenopausal. After the end of the study treatment period, standard adjuvant endocrine therapy was continued for a duration of at least 5 years if deemed medically appropriate.
The major efficacy outcome measure was invasive disease–free survival (IDFS). IDFS was defined as the time from randomization to the first occurrence of: ipsilateral invasive breast tumor recurrence, regional invasive breast cancer recurrence, distant recurrence, contralateral invasive breast cancer, second primary non-breast invasive cancer, or death attributable to any cause. Overall survival (OS) was an additional outcome measure.
A statistically significant difference in IDFS was observed in the intent-to-treat (ITT) population which was primarily attributed to the patients treated in cohort 1. While the OS data in cohort 2 remains immature, more deaths were observed among those receiving VERZENIO plus standard endocrine therapy compared to those receiving standard endocrine therapy alone (10/253 vs. 5/264).
Of 5637 patients randomized, 5120 (91%) were randomized in cohort 1. Patient median age was 51 years (range, 22-89 years), 99% were women, 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 received prior chemotherapy (37% neoadjuvant, 59% adjuvant) and prior radiotherapy (96%). Sixty-five percent of the patients had 4 or more positive lymph nodes with 22% having ≥10 positive lymph nodes, 41% had Grade 3 tumor, and 24% had pathological tumor size ≥50 mm. The majority of patients (99%) had estrogen receptor positive disease and 87% had progesterone receptor positive disease. Initial endocrine therapy received by patients included letrozole (39%), tamoxifen (31%), anastrozole (22%), or exemestane (8%).
Efficacy results for cohort 1 are summarized in Table 16and Figure 1. At the time of OS interim analysis 2, OS was immature and a total of 315 (6%) of patients had died in cohort 1.
Table 16: Efficacy Results in monarchE in Cohort 1 Abbreviation: CI = confidence interval.
VERZENIO PlusTamoxifen or an Aromatase InhibitorN=2555Tamoxifen or an Aromatase InhibitorN=2565Invasive Disease–Free Survival (IDFS)Number of patients with an event, n (%) 317 (12) 474 (18) Hazard ratio (95% CI) 0.65 (0.57, 0.75) IDFS at 48 months, % (95% CI)85.5 (83.8, 87.0) 78.6 (76.7, 80.4) Figure 1: Kaplan-Meier Curves of Invasive Disease–Free Survival VERZENIO plus Tamoxifen or an Aromatase Inhibitor versus Tamoxifen or an Aromatase Inhibitor in Cohort 1 (monarchE)
Figure 1 - in combination with an aromatase inhibitor as initial endocrine-based therapy for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer. ()
- in combination with fulvestrant for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer with disease progression following endocrine therapy. ()
- as monotherapy for the treatment of adult patients with HR-positive, HER2-negative advanced or metastatic breast cancer with disease progression following endocrine therapy and prior chemotherapy in the metastatic setting. ()