On the 1st of January 2020 abemaciclib became listed on the Pharmaceutical Benefits Scheme (PBS) for first-line treatment for non-premenopausal people newly diagnosed with hormone receptor positive, HER2-negative locally advanced or metastatic breast cancer, when taken in combination with anastrozole or letrozole. If anastrozole or letrozole is not appropriate, abemaciclib can be given in combination with fulvestrant or other endocrine therapy; however, the patient will not qualify for abemaciclib on the PBS.
Mechanism of Action
Abemaciclib is a small molecule inhibitor of cyclin-dependent kinases 4 and 6. In breast cancer, this mechanism of inhibition has shown to block progression from G1 into S phase of the cell cycle, leading to cell cycle arrest, senescence, apoptosis and subsequent suppression of tumour growth.
Clinical Trial Data
Abemaciclib indicated for women with hormone receptive positive and HER2-negative locally advanced breast cancer has been assessed in three clinical trials; MONARCH 1,2, and 3. MONARCH 2 and 3 were of particular importance as these clinical trials compared abemaciclib to placebo, in combination with fulvestrant (MONARCH 2) or aromatase inhibitors; anastrozole/letrozole (MONARCH 3). In MONARCH 2 and 3, the objective response rate and median progression-free survival were higher in the abemaciclib combination treatment arms.
The initial dose of abemaciclib is 150mg twice daily (with or without food) and is to be taken in combination with endocrine therapy (anastrozole, letrozole or fulvestrant). If patients experience side effects, dosage reductions in 50mg increments can occur (i.e. 150mg twice daily to 100mg twice daily). However, abemaciclib should be discontinued if patients cannot tolerate 50mg twice daily.
Abemaciclib is primarily metabolised in the liver by CYP3A4. Consequently, any medications which inhibit or induce CYP3A4 will affect abemaciclib drug levels. Additionally, the major active metabolites of abemaciclib inhibit the renal transporters organic cation transporter 2 (OCT2) and multidrug and extrusion toxin protein (MATE1) and MATE2-K. Consequently, medications that are substrates of these transporters could be affected by abemaciclib co-administration.
The most common adverse effects of abemaciclib include:
- Diarrhoea – onset is usually within six to eight days of commencing treatment. At the first sign of loose stools, fluids and antidiarrheal medication (e.g. loperamide) should be commenced;
- Neutropenia – onset is approximately one month after starting treatment. Blood tests should be completed at baseline and monitored regularly throughout treatment;
- Infections, interstitial lung disease and pneumonitis – monitor patients closely for pulmonary symptoms;
- Hepatotoxicity – elevations in ALT and AST can occur, monitor closely. In patients with severe hepatic impairment, dosing should be reduced to once daily;
- Venous thromboembolism;
- Vomiting; and
- Hair loss.
Abemaciclib is the third cyclin-dependent kinase inhibitor to be listed on the PBS, and it is optimistic to see increased PBS options for patients with locally advanced/metastatic breast cancer.
- Australian Prescriber. Abemaciclib for breast cancer. Aust Prescr. 2020; 43: 94-5.
- Breast Cancer Network Australia. Abemaciclib listed for first-line treatment on PBS. BCNA NEWS [Internet]; 2020.
- Verenzio™ (Abemaciclib) Australian approved product information. Tablet [package insert on the internet]. West Ryde: Eli Lilly Australia Pty Ltd. Approved May 2020.