Gedatolisib

REVTORPYK is indicated in combination with fulvestrant, with or without palbociclib, for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer without a PIK3CA mutation detected following progression on or after treatment with at least one line of endocrine therapy in the metastatic setting. REVTORPYK is a kinase inhibitor indicated in combination with fulvestrant, with or without palbociclib, for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer without a PIK3CA mutation detected following progression on or after treatment with at least one line of endocrine therapy in the metastatic setting.

Gedatolisib is a kinase inhibitor of class I PI3K isoforms (α, β, δ, γ) and mTOR complexes mTORC1 and mTORC2, resulting in downstream inhibition of multiple effectors, including AKT. In estrogen receptor (ER)-positive breast cancer cell lines and xenograft models harboring wild-type or mutant PIK3CA, gedatolisib induced apoptosis and anti-proliferative effects in vitro and reduced tumor cell growth in vivo. In a human ER-positive breast cancer xenograft model harboring a PIK3CA mutation, the combination of gedatolisib with palbociclib and fulvestrant increased tumor growth inhibition compared to each treatment alone or the doublet combinations.

Recommended dosage: 180 mg intravenously as a 30-minute infusion once weekly on Days 1, 8, and 15 of a 28-day cycle. Prophylactically initiate steroid-containing alcohol-free mouthwash to reduce the incidence and severity of stomatitis. See Full Prescribing Information for dosage modifications due to adverse reactions. See Full Prescribing Information for instructions on preparation and administration.

None. None.

Stomatitis: REVTORPYK can cause severe stomatitis, including mouth ulcers. Initiate steroid-containing alcohol-free mouthwash prior to starting treatment. Withhold, reduce dose, or permanently discontinue REVTORPYK based on severity. Dermatologic Adverse Reactions: REVTORPYK can cause severe rash. Monitor patients for rash and infectious sequelae. Instruct patients to limit sun exposure during REVTORPYK treatment. Hyperglycemia: REVTORPYK can cause severe hyperglycemia. Evaluate blood glucose levels and hemoglobin A1c prior to starting and at regular intervals during treatment. Embryo-Fetal Toxicity: REVTORPYK can cause fetal harm. Advise patients of potential risk to a fetus and to use effective contraception. Refer to the Prescribing Information of palbociclib and fulvestrant for pregnancy and contraception information.

The following clinically significant adverse reactions are described elsewhere in the labeling: Stomatitis Dermatologic adverse reactions Hyperglycemia The most common (≥20%) adverse reactions, including laboratory abnormalities when given in combination with fulvestrant and palbociclib were decreased white blood cells, decreased neutrophils, decreased hemoglobin, decreased lymphocytes, stomatitis, nausea, decreased platelets, increased fasting glucose, fatigue, vomiting, rash, constipation, diarrhea, increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST), musculoskeletal pain, decreased sodium, and increased eosinophils.

Store at 20°C to 25°C (68°F to 77°F), excursions permitted 15°C to 30°C (59°F to 86°F). Store vial in original carton until time of reconstitution.