VERZENIO

What it is

VERZENIO is an abemaciclib tablet available in 50 mg, 100 mg, and 150 mg film-coated formulations . Abemaciclib is an inhibitor of cyclin D-dependent kinases 4 and 6 (CDK4 and CDK6) . It prevents Rb phosphorylation, blocking progression from G1 into S phase of the cell cycle, leading to suppression of tumour growth .

Approved indications

— Adjuvant treatment of patients with hormone receptor (HR) positive, human epidermal growth factor receptor 2 (HER2) negative, node-positive early breast cancer at high risk of recurrence, in combination with endocrine therapy . — Treatment of hormone receptor (HR) positive, human epidermal growth factor receptor 2 (HER2) negative, locally advanced or metastatic breast cancer either in combination with an aromatase inhibitor or fulvestrant as initial endocrine-based therapy, or following prior endocrine therapy .

Dosing overview

The recommended dose of VERZENIO is 150 mg orally twice daily, in combination with endocrine therapy at its recommended dose . VERZENIO may be taken with or without food . For early breast cancer, VERZENIO should be taken continuously for two years, or until disease recurrence or unacceptable toxicity occurs whichever comes first . For advanced or metastatic breast cancer, it is recommended that treatment be continued until disease progression or unacceptable toxicity .

Key safety warnings

Grade ≥3 neutropenia was reported in patients receiving abemaciclib in breast cancer studies. Complete blood counts should be monitored prior to starting abemaciclib therapy, every 2 weeks for the first 2 months, monthly for the next 2 months, and as clinically indicated . Fatal events of neutropenic sepsis occurred in less than 1% of patients with metastatic breast cancer. Patients should be instructed to report any episode of fever to their healthcare provider . Diarrhoea is the most common adverse reaction. Across clinical studies, median time to onset of the first diarrhoea event was approximately 6 to 8 days, and median duration of diarrhoea was 7 to 12 days (Grade 2) and 5 to 8 days (Grade 3) . Diarrhoea can be associated with dehydration. Patients should start treatment with antidiarrhoeal agents such as loperamide at the first sign of loose stools, increase oral fluids and notify their healthcare provider . Severe, life threatening or fatal interstitial lung disease (ILD) and/or pneumonitis can occur in patients treated with VERZENIO. In early breast cancer (monarchE), 3.2% of patients experienced ILD/pneumonitis of any grade: 0.4% were Grade 3 or 4 and there was one fatality. In metastatic breast cancer (MONARCH 1, MONARCH 2, MONARCH 3), 3.3% of VERZENIO-treated patients had ILD/pneumonitis of any grade, 0.6% had grade 3 or 4, and 0.4% had fatal outcomes . In early stage breast cancer, venous thromboembolic events of any grade were reported in 2.5% of patients treated with adjuvant abemaciclib plus endocrine therapy and 0.6% with endocrine therapy alone . In metastatic breast cancer, venous thromboembolic events were reported in 5.3% of patients treated with abemaciclib plus fulvestrant or aromatase inhibitors, compared to 0.8% of patients treated with placebo plus fulvestrant or aromatase inhibitors .

Contraindications

VERZENIO is contraindicated in patients with hypersensitivity to the active substance or to any of the excipients .

PBS listing

All three strengths (50 mg, 100 mg, and 150 mg tablets) are listed on the PBS with authority required restriction. The ex-manufacturer price for all strengths is A$3883.46 .

Regulatory history

VERZENIO (abemaciclib) was first listed on the ARTG on 8 April 2019 across three strengths: 50 mg, 100 mg, and 150 mg tablets . In November 2017, PBAC did not recommend the medicine for HR-positive, HER2-negative advanced or metastatic breast cancer due to uncertain cost-effectiveness and clinical benefit in the proposed population . In March 2019, PBAC recommended VERZENIO for treatment of non-premenopausal patients with HR-positive, HER2-negative locally advanced or metastatic breast cancer with authority required listing on a cost minimisation basis to ribociclib and palbociclib . An AusPAR approval was issued on 25 May 2022 for VERZENIO in combination with endocrine therapy for the adjuvant treatment of patients with HR-positive, HER2-negative, node-positive early breast cancer at high risk of recurrence . In November 2023, PBAC recommended VERZENIO for general schedule authority required listing for the treatment of HR-positive, HER2-negative lymph node-positive, invasive, resected early breast cancer at high risk of disease recurrence .