AHFS Class:

• Antineoplastic Agents 10:00

Brands:

• Revtorpyk^®

Generic Name(s):

• Gedatolisib

Gedatolisib, a kinase inhibitor, is an antineoplastic agent.1

Gedatolisib has the following uses:

Gedatolisib 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. 1

General

Gedatolisib is available in the following dosage form(s) and strength(s):

For injection:180 mg gedatolisib in a lyophilized powder in a single-dose vial.1

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Adults

Dosage and Administration

• Select patients for treatment of HR-positive, HER2-negative locally advanced or metastatic breast cancer with gedatolisib based on the absence of detected PIK3CA mutations in breast cancer.1
• Recommended dosage is 180 mg as a 30-minute IV infusion once weekly on Days 1, 8, and 15 of a 28-day cycle, in combination with fulvestrant, with or without palbociclib, until disease progression or unacceptable toxicity.1
• Reconstitute and further dilute the drug prior to IV infusion.1
• Prophylactically initiate steroid-containing alcohol-free mouthwash to reduce the incidence and severity of stomatitis.1
• See Full Prescribing Information for additional details on preparation, administration, and dosage modifications for adverse reactions.1

Contraindications

None.1

Warnings/Precautions

Stomatitis

Gedatolisib can cause severe stomatitis, including ulcers and oral mucositis.1 In the principal efficacy study, stomatitis occurred in 72% of patients treated with gedatolisib with fulvestrant and palbociclib, including Grade 3 events in 22% of patients.1 Prophylactic steroid-containing alcohol-free mouthwash was required for a minimum of 8 weeks.1 The median time to onset was 7 days (range: 1 to 457 days).1 Stomatitis led to gedatolisib dose reduction in 19% and permanent discontinuation in 3.8% of patients.1 Stomatitis occurred in 58% of patients treated with gedatolisib with fulvestrant, including Grade 3 events in 12% of patients.1 The median time to onset was 4 days (range: 1 to 524 days).1 Stomatitis led to gedatolisib dose reduction in 9% and permanent discontinuation in 1.5% of patients.1

Prophylactically initiate steroid-containing alcohol-free mouthwash to reduce the incidence and severity of stomatitis.1 If stomatitis occurs, increase the frequency of mouthwash and administer other topical treatments as clinically indicated.1 Withhold, reduce dose, or permanently discontinue gedatolisib based on severity.1

Dermatologic Adverse Reactions

Gedatolisib can cause severe rash.1 In the principal efficacy study, rash occurred in 30% of patients treated with gedatolisib in combination with fulvestrant and palbociclib, including Grade 3 events in 6% of patients.1 The median time to onset was 21 days (range: 3 to 260 days) after starting the drug.1 Rash led to gedatolisib dose reduction in 5% and permanent discontinuation in 0.8% of patients.1 Rash occurred in 40% of patients treated with gedatolisib in combination with fulvestrant, including Grade 3 events in 5% of patients.1 Rash led to gedatolisib dose reduction in 6% and permanent discontinuation in 0.8% of patients.1 The median time to onset was 31.5 days (range: 2 to 407 days) after starting gedatolisib.1

Monitor patients receiving gedatolisib for rash and infectious sequelae.1 Instruct patients to limit sun exposure during gedatolisib treatment.1

Withhold, reduce dose, or permanently discontinue gedatolisib based on severity.1

Hyperglycemia

Severe hyperglycemia can occur in patients treated with gedatolisib.1 Hyperglycemia is associated with drugs that inhibit the PI3K/AKT/mTOR pathway.1

In the principal efficacy study, increased fasting glucose (FG) from baseline occurred in 46% of patients treated with gedatolisib in combination with fulvestrant and palbociclib, including Grade 1 (FG >ULN to 160 mg/dL) in 36% of patients, Grade 2 (FG >160 to 250 mg/dL) in 8% of patients and Grade 3 (FG >250 to 500 mg/dL) in 0.9% of patients.1 Increased fasting glucose from baseline occurred in 57% of patients treated with gedatolisib in combination with fulvestrant, including Grade 1 in 44% of patients, Grade 2 in 11% of patients and Grade 3 in 1.8% of patients.1 The safety of gedatolisib in patients with Type 1 or uncontrolled Type 2 diabetes mellitus has not been established as these patients were excluded from the study.1

Before initiating treatment with gedatolisib, test fasting glucose levels (FPG or FBG), HbA1c levels, and optimize fasting glucose.1 Achieve optimal glucose control before starting each gedatolisib infusion.1 Manage hyperglycemia with anti-hyperglycemic medications.1 Patients with a history of well-controlled Type 2 diabetes mellitus may require intensified anti-hyperglycemic treatment and close monitoring of FG levels.1 Consider consultation with a healthcare professional experienced in the treatment of hyperglycemia.1 Initiate at-home glucose monitoring for patients with HbA1c level >6.4%.1 Advise patients of the signs and symptoms of hyperglycemia and counsel patients on lifestyle changes.1 Withhold, reduce dose, or permanently discontinue gedatolisib based on severity.1

Embryo-fetal Toxicity

Based on its mechanism of action, gedatolisib can cause fetal harm when administered to a pregnant woman.1 Inhibition of PI3K and mTOR pathways have been associated with adverse embryo-fetal growth and lethality in animals.1

Advise patients of the potential risk to a fetus.1 Advise females of reproductive potential to use effective contraception during treatment with gedatolisib and for 2 weeks after the last dose.1 Advise male patients with female partners of reproductive potential to use effective contraception during treatment with gedatolisib and for 2 weeks after the last dose.1

Gedatolisib is used in combination with fulvestrant, with or without palbociclib.1 Refer to the Prescribing Information of fulvestrant and palbociclib for pregnancy and contraception information.1 When gedatolisib is used in combination, advise patients to use effective contraception during treatment and for the longest post-treatment duration recommended in the Prescribing Information of any of the individual products.1

Specific Populations

Pregnancy

Gedatolisib is used in combination with fulvestrant, with or without palbociclib.1 Refer to the Prescribing Information for fulvestrant and palbociclib for pregnancy information.1 When used in combination with gedatolisib, advise patients to use effective contraception during treatment and for the longest post-treatment duration recommended in the Prescribing Information of any of the individual products.1

Based on its mechanism of action, gedatolisib can cause fetal harm when administered to a pregnant woman.1 There are no available data in pregnant women to inform the drug-associated risk.1 Animal reproductive toxicity studies have not been conducted with gedatolisib.1 Inhibition of PI3K and mTOR pathways have been associated with adverse embryo-fetal growth and lethality in animals1

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.1

Lactation

Gedatolisib is used in combination with fulvestrant, with or without palbociclib.1 Refer to the Prescribing Information for fulvestrant and palbociclib for lactation information.1 When used in combination with gedatolisib, advise patients to not breastfeed during treatment and for the longest post-treatment duration recommended in the Prescribing Information of any of the individual products.1

There are no data on the presence of gedatolisib or its metabolites in human milk, its effects on milk production, or a breastfed child.1 Because of the potential for serious adverse reactions in a breastfed child, advise lactating women to not breastfeed during treatment with gedatolisib and for 2 weeks after the last dose.1

Females and Males of Reproductive Potential

Gedatolisib is used in combination with fulvestrant, with or without palbociclib.1 Refer to the Prescribing Information for fulvestrant and palbociclib for contraception and infertility information.1 When used in combination with gedatolisib, advise patients to use effective contraception during treatment and for the longest post-treatment duration recommended in the Prescribing Information of any of the individual products.1

Based on its mechanism of action, gedatolisib can cause fetal harm when administered to a pregnant woman.1

Verify the pregnancy status of females of reproductive potential prior to initiating treatment with gedatolisib.1 Advise females of reproductive potential to use effective contraception during treatment with gedatolisib and for 2 weeks after the last dose.1 Advise male patients with female partners of reproductive potential to use effective contraception during treatment with gedatolisib and for 2 weeks after the last dose.1

Based on animal studies, gedatolisib may impair fertility in females and males of reproductive potential.1 Findings in animals were reversible.1

Pediatric Use

The safety and efficacy of gedatolisib in pediatric patients have not been established.1

Geriatric Use

Of 260 patients who received gedatolisib, 55 patients (21%) were ≥65 and <75 years of age and 17 patients (6.5%) were ≥75 years of age.1

In patients treated with gedatolisib in combination with fulvestrant and palbociclib, the incidence of Grade ≥3 stomatitis and rash was higher in patients ≥65 years of age (37% and 11%, respectively) compared to younger patients (16% and 4.3%, respectively).1 In patients treated with gedatolisib in combination with fulvestrant, the incidence of Grade ≥3 stomatitis and rash was higher in patients ≥65 years of age (18% and 12%, respectively) compared to younger patients (10% and 3.1%, respectively).1 No overall differences in effectiveness of gedatolisib were observed between patients ≥65 years of age and younger patients.1

Common Adverse Effects

• 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. 1
• The most common (≥20%) adverse reactions, including laboratory abnormalities when given in combination with fulvestrant were stomatitis, increased fasting glucose, increased eosinophils, decreased hemoglobin, nausea, rash, increased ALT, fatigue, musculoskeletal pain, decreased lymphocytes, vomiting, increased AST, pruritus, and diarrhea.1

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

Please see product labeling for drug interaction information.

Actions

Mechanism of Action

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.1 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.1 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.1

Advice to Patients

• Advise the patient to read the FDA-approved patient labeling (Patient Information).1
• Inform patients of the risk of stomatitis.1 Advise patients to contact their healthcare provider if they experience any symptoms (e.g., painful redness, swelling, or sores in the mouth).1 Inform patients to use steroid-containing mouthwash for prophylaxis and treatment of stomatitis.1 Instruct patients not to eat or drink for at least 1 hour after administration of the steroid-containing mouthwash.1
• Inform patients of the risks of dermatologic adverse reactions, including rash. Advise patients to limit sun exposure during treatment.1 Advise patients to contact their healthcare provider immediately if they develop a new rash.1
• Inform patients of the risks of hyperglycemia and the need for monitoring of fasting blood glucose and HbA1c periodically during treatment.1 Advise patients to contact their healthcare provider immediately for signs and symptoms of hyperglycemia (e.g., excessive thirst, urinating more often, blurred vision, confusion, difficulty breathing, or increased appetite with weight loss).1
• Inform pregnant women and females of reproductive potential of the potential risk to a fetus.1 Advise females to inform their healthcare provider of a known or suspected pregnancy.1
• Advise females of reproductive potential to use effective contraception during treatment with gedatolisib and for 2 weeks after the last dose.1
• Advise male patients with female partners of reproductive potential to use effective contraception during treatment with gedatolisib and for 2 weeks after the last dose.1
• Refer to the Prescribing Information of palbociclib and fulvestrant for pregnancy and contraception information.1 When used in combination with gedatolisib, advise patients to use effective contraception during treatment and for the longest post-treatment duration recommended in the Prescribing Information of any of the individual products.1
• Advise women not to breastfeed during treatment with gedatolisib and for 2 weeks after the last dose.1 Refer to the Prescribing Information of palbociclib and fulvestrant for lactation information.1 When used in combination, advise patients not to breastfeed during treatment and for the longest post-treatment duration recommended in the Prescribing Information of any of the individual products.1
• Advise females and males of reproductive potential that gedatolisib may impair fertility.1 Refer to the Prescribing Information of palbociclib and fulvestrant for infertility information.1

Additional Information

AHFS first Release^™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

1. Celcuity Inc. REVTORPYK^® (gedatolisib) INTRAVENOUS prescribing information. 2026 Jul. [Web]