FDA approves Verzenio as the first and only CDK4/6 inhibitor for certain people with HR+HER2- high-risk early breast cancer

Verzenio phase-III monarchE trial is a randomised (1:1), open-label, two cohort, multi-centre 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
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The US Food and Drug Administration (FDA) has approved Eli Lilly’s 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 per cent as determined by an FDA-approved test. Ki-67 is a marker of cellular proliferation. Verzenio is the first and only CDK4/6 inhibitor approved for this patient population, a statement from Eli Lily informed.

“Over time, the collective results of the Verzenio clinical development programme 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,” said Jacob Van Naarden, Senior Vice President, CEO, Loxo Oncology, Lilly and President, Lilly Oncology.

“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,” he added.

The statement said that the Verzenio phase-III monarchE trial is a randomised (1:1), open-label, two cohort, multi-centre 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 randomised to receive two years of Verzenio 150 mg twice daily plus physician’s choice of standard endocrine therapy, or standard endocrine therapy alone. Patients in both treatment arms were instructed to continue to receive adjuvant endocrine therapy for up to five-to-10 years as recommended by their clinician. The primary endpoint of the study is invasive disease-free survival (IDFS) and was met at a pre-specified interim analysis in the intent-to-treat (ITT) population, with a statistically significant improvement in IDFS for patients treated with Verzenio plus ET compared to those treated with ET alone. Consistent with expert guidelines, IDFS was defined as the length of time before breast cancer comes back, any new cancer develops, or death.

Having achieved the study’s primary endpoint in the entire enrolled population, a pre-specified analysis of IDFS was also conducted in patients with high-risk clinical and pathological factors and a Ki-67 score ≥20 per cent. This subgroup analysis (N=2,003) included patients with ≥4 positive axillary lymph nodes (ALN), or 1-3 positive ALN with either Grade 3 disease and/or tumour size ≥5 cm, and whose tumors had a Ki-67 score of ≥20 per cent. There was also a statistically significant improvement in IDFS for this pre-specified subgroup of patients receiving Verzenio plus ET compared to those who received ET alone (HR=0.643, 95% CI: 0.475, 0.872, p=0.0042), added the statement.

This approval is based on efficacy results from an analysis of this subgroup with additional follow-up, conducted post-hoc. In this analysis, Verzenio, given in combination with ET, continued to demonstrate a clinically meaningful benefit, with a 37 per cent decrease in the risk of breast cancer recurrence or death compared to standard adjuvant ET alone for patients with high risk clinical and pathological features and a Ki-67 score ≥20 per cent (HR: 0.626 [95% CI: 0.49-0.80]), and an absolute benefit in IDFS event rate of 7.1 percent at three years. The number of IDFS events at the time of this analysis was 104 with Verzenio plus ET compared to 158 with ET alone. The overall survival data were not mature and additional follow up is ongoing, it further said.

Further, according to the statement, adverse reactions from monarchE were consistent with the known safety profile for Verzenio. Safety and tolerability were evaluated in 5,591 patients. The most common adverse reactions reported (>10 per cent) in the Verzenio plus ET (tamoxifen or an aromatase inhibitor) arm, and >2 per cent 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 per  cent) were creatinine increased, white blood cell count decreased, neutrophil count decreased, anemia, lymphocyte count decreased, platelet count decreased, ALT increased, AST increased and hypokalemia.

The statement also said that this FDA approval builds on the established body of evidence for Verzenio, which is already approved for the treatment of certain types of HR+ HER2- advanced or metastatic breast cancer. Concurrent with this approval, the FDA has expanded the use of Verzenio in all indications, when given in combination with endocrine therapy, to include men. Verzenio is available in tablet strengths of 200 mg, 150 mg, 100 mg and 50 mg.

“The design and results of the monarchE study are practice-changing and represent the first advancement in adjuvant treatment of HR+ HER2- breast cancer in a very long time,” said Sara M Tolaney, MD, MPH, Harvard Medical School, Dana-Farber Cancer Institute and investigator on the monarchE study. “This FDA approval for Verzenio, in combination with endocrine therapy in the early breast cancer setting, has the potential to become a new standard of care for this population. We are encouraged by the marked reduction in the risk of recurrence even beyond the two-year treatment period in these patients, and I’m grateful to be able to offer this as a treatment option to my patients.

“Women and men living with high-risk HR+ HER2- early breast cancer want to do all they can to reduce the risk of the disease coming back, with the hope of living free of cancer. The approval of Verzenio provides a new treatment option to help them do just that,” said Jean Sachs, Chief Executive Officer, Living Beyond Breast Cancer.

clinical trialEli Lilyendocrine therapymonarchE studyUS FDAVerzenio
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