On October 13, 2021, the manufacturer, Eli Lilly, announced that the FDA approved Verzenio (abemaciclib) in combination with endocrine therapy (tamoxifen or an aromatase inhibitor) for the adjuvant treatment of adult patients with hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2–), node-positive, early breast cancer (EBC) at high risk of recurrence and a Ki-67 score of >20% as determined by an FDA-approved test. Ki-67 is a marker of cellular proliferation.

Abemaciclib is the first and only CDK4/6 inhibitor (drugs designed to interrupt cancer cell growth by targeting enzymes called CDK4 and CDK6) approved by the FDA for this specific patient population. Abemaciclib is the first addition to adjuvant endocrine therapy approved by the FDA in nearly two decades for the treatment of HR+ HER2– EBC.

Jacob Van Naarden, senior vice president, CEO, of Loxo Oncology at Lilly and president, Lilly Oncology, stated, "Over time, the collective results of the Verzenio clinical development program have demonstrated a differentiated CDK4/6 inhibitor profile, and the landmark data from the monarchE trial that supported this new indication in HR+ HER2- early breast cancer represent another important step forward for people who are in need of new treatment options. We are pleased with this initial approval in the adjuvant setting and as these data continue to mature, we look forward to further opportunities to work with health authorities to expand the use of Verzenio in this setting."

The Verzenio phase III monarchE trial is a randomized (1:1), open-label, two cohort, multicenter study in adult women and men with HR+ HER2-, node-positive, resected EBC with clinical and pathological features consistent with a high risk of disease recurrence.

In the trial, patients were randomized to receive 2 years of abemaciclib 150 mg twice daily plus physician's choice of standard endocrine therapy (ET) or standard ET alone. Patients in both treatment arms were instructed to continue to receive adjuvant ET for up to 5 to 10 years as recommended by their clinician. The primary endpoint of the study was invasive disease-free survival (IDFS), which was met at a prespecified interim analysis in the intent-to-treat population, with a statistically significant improvement in IDFS for patients treated with abemaciclib plus ET compared to those treated with ET alone. Consistent with expert guidelines, IDFS was defined as the length of time before breast cancer recurs, any new cancer develops, or death.

Having achieved the study's primary endpoint in the entire enrolled population, a prespecified analysis of IDFS was also conducted in patients with high-risk clinical and pathological factors and a Ki-67 score >20%. This subgroup analysis (n = 2,003) included patients with >4 positive axillary lymph nodes (ALN), or 1-3 ALN with either Grade 3 disease and/or tumor size ³5 cm, and whose tumors had a Ki-67 score of >20%. There was also a statistically significant improvement in IDFS for this prespecified subgroup of patients receiving abemaciclib plus ET compared with those who received ET alone (hazard ratio = 0.643, 95% CI: 0.475, 0.872, P = .0042).

Adverse reactions from monarchE were consistent with the known safety profile for abemaciclib. Safety and tolerability were evaluated in 5,591 patients, and the most common adverse reactions reported (>10%) in the abemaciclib plus ET (tamoxifen or an aromatase inhibitor) arm and >2% higher than the ET arm alone were diarrhea, infections, fatigue, nausea, headache, vomiting, stomatitis, decreased appetite, dizziness, rash, and alopecia.

The most common laboratory abnormalities (all grades >10%) were increased creatinine, decreased white blood cell count, decreased neutrophil count, anemia, lymphocyte count decreased, decreased platelet count, increased alanine transaminase, increased aspartate transaminase, and hypokalemia.

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