Abeclib 200

Breast Cancer

May take with or without food Instruct patient to take dose at approximately the same time each day

Breast Cancer Indicated for HR+/HER2- advanced or metastatic breast cancer with disease progression following endocrine therapy as either monotherapy or in combination with fulvestrant Also, indicated in combination with an aromatase inhibitor as initial endocrine-based therapy for postmenopausal women with HR+/HER2- advanced or metastatic breast cancer Monotherapy 200 mg PO BID Continue until disease progression or unacceptable toxicity Combination therapy With aromatase inhibitor Abemaciclib: 150 mg PO BID PLUS Aromatase inhibitor: See Prescribing Information Continue until disease progression or unacceptable toxicity With fulvestrant Abemaciclib: 150 mg PO BID PLUS Fulvestrant: 500 mg IM on Days 1, 15, and 29, and then once monthly thereafter Continue until disease progression or unacceptable toxicity Hepatic impairment Mild or moderate (Child-Pugh A or B): No dose adjustment required Severe (Child-Pugh C): Reduce dosing frequency to once daily

Renal impairment Mild or moderate (CrCl 30-89 mL/min): No dose adjustment required Severe, ESRD, or dialysis: Not studied

Inhibits cyclin-dependent kinases (CDKs) 4 and 6 These kinases are activated upon binding to D cyclins and play a crucial role in signaling pathways, which lead to cell cycle progression and cellular proliferation In ER-positive breast cancer cells, cyclin D1 and CDK4/6 promote phosphorylation of the retinoblastoma protein (Rb), cell cycle progression, and cell proliferation

Venous thromboembolism In clinical trials, venous thromboembolic events (VTE) reported in patients treated with abemaciclib plus an aromatase inhibitor (5%) and in patients treated with abemaciclib plus fulvestrant (5%) VTE (eg, deep vein thrombosis, pulmonary embolism, cerebral venous sinus thrombosis, pelvic venous thrombosis, subclavian and axillary vein thrombosis, inferior vena cava thrombosis) reported in patients receiving abemaciclib and fulvestrant Monitor for signs and symptoms of venous thrombosis and pulmonary embolism and appropriately treat Hepatotoxicity Increased transaminases were observed in clinical trials In patients who had grade ≥3 ALT elevation, median time-to-onset was 57 days; whereas, grade <3 was 14 days In patients who had grade ≥3 AST elevation, median time-to-onset was 185 days; whereas, grade <3 was 13 days Neutropenia Neutropenia observed in clinical trials; in patients with grade >3 neutropenia, median time time-to-onset was 29 days and median duration was 15 days Febrile neutropenia reported in <1% of patients exposed to abemaciclib in the MONARCH studies; 2 deaths due to neutropenic sepsis were observed in MONARCH 2 Diarrhea Diarrhea occurred in 81% of patients receiving abemaciclib plus an aromatase inhibitor in MONARCH 3, 86% of patients receiving abemaciclib plus fulvestrant in MONARCH 2, and 90% of patients receiving abemaciclib alone in MONARCH 1 Episodes of diarrhea have been associated with dehydration and infection; diarrhea incidence was greatest during the first month of dosing

>10% (Monotherapy) Creatinine increased (98%) Diarrhea (90%) Decreased WBCs (91%) Decreased neutrophil count (88%) Anemia (68%) Fatigue (65%) Nausea (64%) Decreased appetite (45%) Decreased lymphocyte count (42%) Decreased platelet count (41%) Abdominal pain (39%) Neutropenia (37%) Vomiting (35%) Infection (31%) ALT increased (31%) AST increased (30%) Decreased WBC, grade 3 (28%) Anemia (25%) Decreased neutrophil count, grade 3 (22%) Thrombocytopenia (20%) Diarrhea, grade 3 (20%) Headache (20%) Cough (19%) Neutropenia, grade 3 (19%) Constipation (17%) Leukopenia (17%) Arthralgia (15%) Dry mouth (14%) Stomatitis (14%) Weight decreased (14%) Decreased lymphocyte count, grade 3 (13%) Dysgeusia (12%) Alopecia (12%) Dizziness (11%) Pyrexia (11%) >10% (Combination Therapy) Creatinine increased (98%) Decreased WBCs (90%) Decreased neutrophil count (80-87%) Diarrhea (86%) Anemia (29-82%) Decreased lymphocyte count (53-63%) Decreased platelet count (36-53%) Neutropenia (46%) Fatigue (46%) Nausea (45%) Infections (43%) ALT increased (13-41%) AST increased (12-37%) Abdominal pain (35%) Decreased neutrophil count, grade 3 (29%) Leukopenia (28%) Decreased appetite (27%) Vomiting (26%) Neutropenia, grade 3 (24%) Decreased WBC, grade 3 (23%) Headache (20%) Dysgeusia (18%) Thrombocytopenia (16%) Alopecia (16%) Stomatitis (15%) Pruritus (13%) Diarrhea, grade 3 (13%) Cough (13%) Dizziness (12%) Decreased lymphocyte count, grade 3 (7-12%) Peripheral edema (12%) Rash (11%) Pyrexia (11%)

Pregnancy There are no available human data informing the drug-associated risk Based on findings from animal studies and the mechanism of action, can cause fetal harm when administered to a pregnant woman In animal data, administration of abemaciclib during organogenesis was teratogenic and caused decreased fetal weight at maternal exposures that were similar to human clinical exposure based on AUC at the maximum recommended human dose Pregnancy testing is recommended for females of reproductive potential prior to initiating treatment Advise females of reproductive potential to use effective contraception during treatment and for at least 3 weeks after the last dose Based on findings in animals, abemaciclib may impair fertility in males of reproductive potential Lactation Unknown if distributed in human breast milk Because of the potential for serious adverse reactions in breastfed infants, advise lactating women not to breastfeed while taking abemaciclib and for at least 3 weeks after the last dose

Ketoconazole: Avoid coadministration Other strong CYP3A inhibitors: Decrease recommended starting dose (see Dosage Modifications) Strong CYP3A inducers: Avoid coadministration