Inavolisib (Monograph)

Brand name: Itovebi
Drug class: Antineoplastic Agents

Medically reviewed by Drugs.com on Dec 10, 2024. Written by ASHP.

Introduction

Inavolisib, a kinase inhibitor, is an antineoplastic agent.

Uses for Inavolisib

Inavolisib has the following uses:

Inavolisib is indicated in combination with palbociclib and fulvestrant for the treatment of adults with endocrine-resistant, PIK3CA-mutated, hormone receptor (HR)-positive, human epidermal growth-factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer, as detected by an FDA-approved test, following recurrence on or after completing adjuvant endocrine therapy.

Inavolisib Dosage and Administration

General

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

Tablets: 3 mg and 9 mg

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 the treatment of HR-positive, HER2-negative, locally advanced or metastatic breast cancer with inavolisib based on the presence of one or more PIK3CA mutations in plasma specimen.
Recommended dosage of inavolisib is 9 mg orally once daily with or without food, until disease progression or unacceptable toxicity.
Swallow tablets whole; do not chew, crush, or split prior to swallowing.
Administer inavolisib in combination with palbociclib and fulvestrant. The recommended dosage of palbociclib is 125 mg taken orally once daily for 21 consecutive days followed by 7 days off treatment to comprise a cycle of 28 days. Refer to the Full Prescribing Information for palbociclib and fulvestrant for dosing information.
For premenopausal and perimenopausal women, administer a luteinizing hormone-releasing hormone (LHRH) agonist in accordance with local clinical practice. For men, consider administering an LHRH agonist in accordance with local clinical practice.
See Full Prescribing Information for dosage modifications of inavolisib due to adverse reactions.
Reduce the starting dose in patients with moderate renal impairment.

Cautions for Inavolisib

Contraindications

None.

Warnings/Precautions

Hyperglycemia

Severe hyperglycemia can occur in patients treated with inavolisib. Increased fasting glucose occurred in 85% of patients treated with inavolisib, including 22% of patients with Grade 2 (FPG > 160 to 250 mg/dL), 12% with Grade 3 (FPG > 250 to 500 mg/dL), and 0.6% with Grade 4 (FPG > 500 mg/dL) events. In the INAVO120 study, 46% (74/162) of patients who received inavolisib were treated with oral anti-hyperglycemic medications and 7% (11/162) were treated with insulin to manage increased fasting glucose. For patients who experienced an increased fasting glucose of >160 mg/dL, 96% (52/54) had an improvement in fasting glucose of at least one grade level with a median time to improvement from the first event of 8 days (range: 2 to 43 days). Among patients with hyperglycemia, the median time to first onset was 7 days (range: 2 to 955 days). Hyperglycemia led to dose interruption in 28%, to dose reduction in 2.5%, and to discontinuation of inavolisib in 1.2% of patients.

The safety of inavolisib in patients with Type 1 diabetes mellitus, or Type 2 diabetes mellitus requiring ongoing systemic therapy have not been studied.

Before initiating treatment with inavolisib, test fasting glucose levels (FPG or FBG), HbA_1C levels, and optimize fasting glucose. After initiating treatment with inavolisib, or in patients who experience hyperglycemia after initiating treatment with inavolisib, monitor or self-monitor fasting glucose levels once every 3 days for the first week (Day 1 to 7), then once every week for the next 3 weeks (Day 8 to 28), then once every 2 weeks for the next 8 weeks, then once every 4 weeks thereafter, and as clinically indicated. Monitor HbA_1C every 3 months and as clinically indicated.

Manage hyperglycemia with anti-hyperglycemic medications as clinically indicated. During treatment with anti-hyperglycemic medication, continue monitoring fasting glucose levels. Patients with a history of well-controlled Type 2 diabetes mellitus may require intensified anti-hyperglycemic treatment and close monitoring of fasting glucose levels. Consider consultation with a healthcare professional experienced in the treatment of hyperglycemia, and initiation of fasting glucose monitoring at home for patients who have risk factors for hyperglycemia or who experience hyperglycemia. Advise patients of the signs and symptoms of hyperglycemia and counsel patients on lifestyle changes. Based on the severity of the hyperglycemia, inavolisib may require dose interruption, reduction, or discontinuation.

Stomatitis

Severe stomatitis can occur in patients treated with inavolisib. Stomatitis occurred in 51% of patients treated with inavolisib in combination with palbociclib and fulvestrant, including Grade 3 events in 6% of patients. The median time to first onset was 13 days (range: 1 to 610 days). Stomatitis led to interruption of inavolisib in 10%, to dose reduction in 3.7%, and to discontinuation of inavolisib in 0.6% of patients. In patients who received inavolisib in combination with palbociclib and fulvestrant, 38% used a mouthwash containing corticosteroid for management or prophylaxis of stomatitis.

Monitor patients for signs and symptoms of stomatitis. Withhold, reduce dose, or permanently discontinue inavolisib based on severity.

Diarrhea

Severe diarrhea including dehydration and acute kidney injury can occur in patients treated with inavolisib. Diarrhea occurred in 48% of patients treated with inavolisib in combination with palbociclib and fulvestrant, including Grade 3 events in 3.7% of patients. The median time to first onset was 15 days (range: 2 to 602 days). Anti-diarrheal medicines were used in 28% (46/162) of patients who received inavolisib in combination with palbociclib and fulvestrant to manage symptoms. Dose interruptions were required in 7% of patients, and dose reductions occurred in 1.2% of patients.

Monitor patients for signs and symptoms of diarrhea. Advise patients to increase oral fluids and start anti-diarrheal treatment at the first sign of diarrhea while taking inavolisib. Withhold, reduce dose, or permanently discontinue inavolisib based on severity.

Embryo-fetal Toxicity

Based on findings in animals and its mechanism of action, inavolisib can cause fetal harm when administered to a pregnant woman. In an animal reproduction study, oral administration of inavolisib to pregnant rats during the period of organogenesis caused adverse developmental outcomes, including embryo-fetal mortality, structural abnormalities, and alterations to growth at maternal exposures approximately equivalent to the human exposure at the recommended dose of 9 mg/day based on AUC.

Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective non-hormonal contraception during treatment with inavolisib and for 1 week after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with inavolisib and for 1 week after the last dose.

Inavolisib is used in combination with palbociclib and fulvestrant. Refer to the Full Prescribing Information of palbociclib and fulvestrant for pregnancy and contraception information.

Specific Populations

Pregnancy

Inavolisib is used in combination with palbociclib and fulvestrant. Refer to the Full Prescribing Information of palbociclib and fulvestrant for pregnancy information.

Based on animal data and its mechanism of action, inavolisib can cause fetal harm when administered to a pregnant woman. There are no available data on the use of inavolisib in pregnant women to inform a drug-associated risk. In an animal reproduction study, oral administration of inavolisib to pregnant rats during the period of organogenesis caused adverse developmental outcomes, including embryo-fetal mortality, structural abnormalities, and alterations to growth at maternal exposures approximately equivalent to the human exposure at the recommended dose of 9 mg/day based on AUC. Advise pregnant women and females of reproductive potential of the potential risk to a fetus.

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

Lactation

Inavolisib is used in combination with palbociclib and fulvestrant. Refer to the Full Prescribing Information of palbociclib and fulvestrant for lactation information.

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

Females and Males of Reproductive Potential

Inavolisib is used in combination with palbociclib and fulvestrant. Refer to the Full Prescribing Information of palbociclib and fulvestrant for contraception and infertility information.

Inavolisib can cause fetal harm when administered to a pregnant woman. Verify pregnancy status in females of reproductive potential prior to initiating treatment with inavolisib. Advise females of reproductive potential to use effective non-hormonal contraception during treatment with inavolisib and for 1 week after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with inavolisib and for 1 week after the last dose.

Based on animal studies, inavolisib may impair fertility in females and males of reproductive potential.

Pediatric Use

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

Geriatric Use

Of the 162 patients who received inavolisib in the INAVO120 study, 15% were ≥ 65 years of age, and 3% were ≥ 75 years of age.

Dosage modifications or interruptions of inavolisib due to adverse reactions occurred at a higher incidence for patients ≥ 65 years of age compared to younger patients (79% versus 68%, respectively).

Clinical studies of inavolisib did not include sufficient numbers of patients 65 years of age and over to determine whether they respond differently from younger patients.

Renal Impairment

Reduce the dosage in patients with moderate renal impairment (eGFR 30 to <60 mL/min based on CKD-EPI). No dosage modification is recommended in patients with mild renal impairment (eGFR 60 to < 90 mL/min). Inavolisib has not been evaluated in patients with severe renal impairment (eGFR <30 mL/min).

Common Adverse Effects

The most common (≥ 20%) adverse reactions, including laboratory abnormalities, were decreased neutrophils, decreased hemoglobin, increased fasting glucose, decreased platelets, decreased lymphocytes, stomatitis, diarrhea, decreased calcium, fatigue, decreased potassium, increased creatinine, increased ALT, nausea, decreased sodium, decreased magnesium, rash, decreased appetite, COVID-19 infection, and headache.

Drug Interactions

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

Inavolisib is an inhibitor of phosphatidylinositol 3-kinase (PI3K) with inhibitory activity predominantly against PI3Kα. In vitro, inavolisib induced the degradation of mutated PI3K catalytic alpha subunit p110α (encoded by the PIK3CA gene), inhibited phosphorylation of the downstream target AKT, reduced cellular proliferation, and induced apoptosis in PIK3CA-mutated breast cancer cell lines. In vivo, inavolisib reduced tumor growth in PIK3CA-mutated, estrogen receptor-positive, breast cancer xenograft models. The combination of inavolisib with palbociclib and fulvestrant increased tumor growth inhibition compared to each treatment alone or the doublet combinations.

Advice to Patients

Advise patients to read the FDA-approved patient labeling (Patient Information).
Advise patients that inavolisib may cause hyperglycemia and the need to monitor fasting glucose levels periodically during therapy. Advise patients to contact their healthcare provider immediately for signs and symptoms of hyperglycemia (e.g., excessive thirst, urinating more often, blurred vision, mental confusion, difficulty breathing, or increased appetite with weight loss).
Advise patients that inavolisib may cause stomatitis, which may be severe, and to notify their healthcare provider if they develop symptoms of stomatitis (e.g., painful redness, swelling, or sores in the mouth).
Advise patients that inavolisib may cause diarrhea, which may be severe, and to start antidiarrheal treatment, increase oral fluids, and notify their healthcare provider if diarrhea occurs while taking inavolisib.
Inform pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females to inform their healthcare provider of a known or suspected pregnancy.
Advise females of reproductive potential to use effective non-hormonal contraception during treatment with inavolisib and for 1 week after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with inavolisib and for 1 week after the last dose. Refer to the Full Prescribing Information of palbociclib and fulvestrant for pregnancy and contraception information.
Advise women not to breastfeed during treatment with inavolisib and for 1 week after the last dose. Refer to the Full Prescribing Information of palbociclib and fulvestrant for lactation information.
Advise females and males of reproductive potential that inavolisib may impair fertility. Refer to the Full Prescribing Information of palbociclib and fulvestrant for infertility information.
Instruct patients to take inavolisib at approximately the same time each day.
Instruct patients that if a dose of inavolisib is missed, to take the missed dose as soon as possible within 9 hours. After more than 9 hours, skip the dose and take the next dose at the scheduled time.
Instruct patients that if vomiting occurs after taking the inavolisib dose, do not take an additional dose on that day. Resume the usual dosing schedule the next day.

Additional Information

AHFSfirstRelease^™. 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.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.