inavolisib (Itovebi)

Indications

• in combination with palbociclib & fulvestrant treatment of endocrine-resistant, PIK3CA-mutated, hormone receptor-positive, HER2-negative, locally advanced or metastatic breast cancer

Contraindications

• pregnancy, embryo-fetal toxicity
• lactation

Dosage

• 9 mg PO QD with or without food
• Tablets: 3 mg, 9 mg

Dosage adjustment in renal failure

• 6 mg orally once daily if eGFR 30-60 mL/min (based on CKD-EPI)

Adverse effects

• stomatitis*, diarrhea, nausea, headache
• hyperglycemia, hypocalcemia. hypokalemia, hyponatremia, hypomagnesemia
• increased serum creatinine, increased serum ALT
• leukopenia, anemia, thrombocytopenia, lymphopenia

* treat stomatitis with glucocorticoid-containing mouthwash

Mechanism of action

• inhibits phosphatidylinositol 3-kinase (PI3K), predominantly PI3K-alpha
  • degrades mutated PI3K-alpha, inhibits phosphorylation of downstream AKT

More general terms

• small inhibitory antineoplastic agent (ib drug)

Database

• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=124173720