7-Year MonarchE Results

Abbreviations: AE=adverse event; AI=aromatase inhibitor; CDK4/6i=cyclin-dependent kinase 4/6 inhibitor; CI=confidence interval; DRFS=distant relapse-free survival; EBC=early breast cancer; EMA=European Medicines Agency; ET=endocrine therapy; HER2−=human epidermal growth factor receptor 2-negative; HR+=hormone receptor-positive; HR=hazard ratio; IDFS=invasive disease-free survival; KM=Kalpan-Meier; QoL=quality of life.

Verzenios® (abemaciclib) film-coated tablets I: Temporarily authorized indication: Adjuvant treatment in combination with endocrine therapy (ET) of adult women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, node-positive early breast cancer at high risk of relapse based on lymph node status, primary tumour size and tumour grade. In pre- or perimenopausal women, aromatase inhibitor endocrine therapy should be combined with a LHRH agonist. Permanent Indication: Treatment of postmenopausal women with HR+, HER2- locally advanced or metastatic breast cancer: in combination with an aromatase inhibitor as initial endocrine-based therapy or in combination with fulvestrant in women who have received prior endocrine therapy. As monotherapy following disease progression after endocrine therapy and one or two chemotherapy regimens in the metastatic setting, when chemotherapy is not suitable. In pre- or perimenopausal women combined with a LHRH-agonist. P: The recommended dose is 150 mg twice daily when used in combination with endocrine therapy and as a single agent 200 mg twice daily.CI: Hypersensitivity. W/P: For women who have not received any (neo-) adjuvant chemotherapy before, the available data is limited, because only 2% of women in the monarchE study were included. No statistically significant overall survival benefit from abemaciclib was shown at temporary approval. Its impact on survival compared to later relapse treatment, or on subsequent advanced cancer therapies, remains unassessed. Neutropenia, infections, Interstitial Lung Disease (ILD)/Pneumonitis, diarrhoea, increased aminotransferases, venous thromboembolism and arterial thromboembolic events occurred. Contains lactose. Verzenios can have an influence on the ability to drive and use machines. IA: Abemaciclib and its circulating active metabolites resulted in a down-regulation of CYPs’ mRNA, including CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2D6, and CYP3A4 in vitro. In a clinical drug interaction study in women with cancer, multiple doses of abemaciclib did not result in clinically meaningful changes in the pharmacokinetics of CYP1A2 (caffeine), CYP2C9 (S-warfarin), CYP2D6 (dextromethorphane) and CYP3A4 substrates (midazolam). The clinical effects of CYP2C8 and CYP2B6 down regulation are unknown. Abemaciclib is a substrate of CYP3A4, time dependent changes in pharmacokinetics of abemaciclib as a result of autoinhibition of its metabolism were not observed. When strong CYP3A4 inhibitors such as for example clarithromycin, itraconazole, ketoconazole, lopinavir/ritonavir, posaconazole or voriconazole need to be co-administered, the dose of abemaciclib should be reduced. Caution and monitoring of toxicity is recommended during concomitant treatment with sensitive substrates of P-gp or BCRP that have a narrow therapeutic index, such as digoxin and dabigatran. Sensitive substrates of P-gp or BCRP that do not have a narrow therapeutic index such as pitavastatin, pravastatin and rosuvastatin may be used with caution. Abemaciclib and its major active metabolites inhibit the renal transporters OCT2, MATE1, and MATE2-K at concentrations achievable at the approved recommended dosage. Pr/L: There are no data from the use of abemaciclib in pregnant women. Animal studies have shown reproduction toxicity. Therefore, Verzenios should not be used during pregnancy and in women of childbearing potential without use of contraception, unless this is absolutely necessary. If Verzenios is used during pregnancy or if a patient gets pregnant during therapy, the patient should be advised of the potential risk for the fetus. It is unknown whether abemaciclib is excreted in human milk. A risk to newborns/infants cannot be excluded. Women should not breast-feed during treatment with abemaciclib and for at least up to 3 weeks after last administration of abemaciclib. ADR: Very common: Infections, neutropenia, anemia, leukopenia, thrombocytopenia, decreased appetite, dysgeusia, dizziness, diarrhoea, nausea, abdominal pain, vomiting, stomatitis, alopecia, rash, pruritus, fatigue, pyrexia, increased ASAT/ALAT. Common: Lacrimation increase, venous thromboembolism, lymphopenia, Interstitial lung disease/pneumonitis, dry mouth, dry skin, muscular weakness. P: 50 mg, 100 mg, 150 mg, 200 mg: 28 and 56 film-coated tablets. Dispensing category A.. Consult www.swissmedicinfo.ch for further information. Eli Lilly (Suisse) SA, ch. des Coquelicots 16, CP 580, 1214 Vernier (GE). V12-2023