Inavolisib, a phosphatidylinositol 3-kinase (PI3K) inhibitor, is an antineoplastic agent.1, 2, 3
Inavolisib is used 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.1, 2, 3
Safety and efficacy of inavolisib in combination with palbociclib and fulvestrant for the treatment of adults with endocrine-resistant, PIK3CA -mutated, HR-positive, HER2-negative, locally advanced or metastatic breast cancer have been established in a phase 3, double-blind, placebo-controlled, randomized study (INAVO120).1, 2, 3 Patients were enrolled in the study if they had disease recurrence or progression during or within 12 months after the completion of adjuvant endocrine therapy, a fasting blood glucose (FBG) <126 mg/dL, and hemoglobin A1C (HbA1C) <6%.1, 2 Patients with type 1 or 2 diabetes mellitus who were receiving anti-hyperglycemic therapy were excluded.1 Patients were randomly assigned to receive inavolisib 9 mg or placebo orally once daily, in combination with palbociclib 125 mg orally once daily for 21 consecutive days followed by 7 days off treatment to complete a cycle of 28 days, and fulvestrant 500 mg administered IM on days 1 and 15 of cycle 1, and then on day 1 of every 28-day cycle.1, 2 Patients received treatment until disease progression or unacceptable toxicity.1, 2 Premenopausal or perimenopausal women and men also received a luteinizing hormone-releasing hormone (LHRH) agonist for hormone suppression throughout therapy.1, 2 The primary efficacy outcome measure was progression-free survival, as assessed by the investigator according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).1, 2 Key secondary endpoints included objective response rate and overall survival.1, 2
Among the 325 patients enrolled in INAVO120, the median age was 54 years (range 27-79 years); 59% were white, 38% were Asian, 98% were female (39% of which were pre-perimenopausal), 63% had an Eastern Cooperative Oncology Group (ECOG) performance status of 0, and 36% had an ECOG performance status of 1.1 The majority (64%) were considered to have secondary endocrine resistance; 83% of patients had received prior chemotherapy and 1.2% of patients had been treated with a cyclin-dependent kinase (CDK) 4/6 inhibitor.1 At the planned interim analysis, patients receiving inavolisib had an improved and statistically significant progression-free survival compared to those receiving placebo (median of 15 versus 7.3 months).1, 2, 3 An objective response occurred in 58% of patients in the inavolisib group and 25% of those in the placebo group; the median duration of response was 18.4 and 9.6 months, respectively.1, 2 Overall survival results were not mature at the time of analysis, with 30% deaths reported in the overall population.1 In the interim analysis for overall survival, the hazard ratio for death (inavolisib versus placebo) was 0.64 with median overall survival not estimable in the inavolisib arm and 31.1 months in the placebo arm.3
Guidelines from the American Society of Clinical Oncology (ASCO) provide recommendations for the treatment of HR-positive, HER2-negative, metastatic breast cancer.5, 26 ASCO recommends a CDK4/6 inhibitor with endocrine therapy as first-line treatment.26 Second and third-line treatment options include targeted therapies (e.g., capivasertib, alpelisib) based on tumor genomics and prior endocrine therapy.26 For patients with tumors harboring PIK3CA who have recurrence while on or with recent exposure to endocrine therapy, the ASCO guideline recommends fulvestrant in combination with capivasertib or fulvestrant in combination with alpelisib.26 Inavolisib is not currently mentioned in the ASCO guidelines.26 Guidelines from the European Society for Medical Oncology (ESMO) recommend combination therapy with fulvestrant, palbociclib, and inavolisib as a treatment option for patients with HR-positive, HER2-negative, metastatic breast cancer who have a PIK3CA mutation.5
Inavolisib is administered orally with or without food at approximately the same time each day.1 The drug is commercially available as 3 mg and 9 mg tablets.1
Swallow tablets whole; do not chew, crush, or split.1
If a dose of inavolisib is missed, the missed dose should be taken as soon as possible within 9 hours.1 If a dose of inavolisib is missed after more than 9 hours, the missed dose should be skipped and the next dose should be taken at the scheduled time.1
If a dose of inavolisib is vomited, patients should not take an extra dose.1 The next dose should be taken at the regularly scheduled time.1
Store inavolisib tablets at 20-25ºC, excursions permitted between 15-30ºC.1
The recommended adult dosage of inavolisib in combination with palbociclib and fulvestrant for the treatment of endocrine-resistant, PIK3CA -mutated, hormone receptor (HR)-positive, human epidermal growth-factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer is 9 mg once daily.1
Treatment should continue until disease progression or unacceptable toxicity.1
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.1 Refer to the full prescribing information for palbociclib and fulvestrant for respective dosing information.1
Dosage Modification for Adverse Reactions
If adverse reactions occur, dosage interruption and/or reduction, or discontinuance of inavolisib may be necessary (see Table 1).1
If dosage reduction from 9 mg once daily is necessary, the dosage should be reduced to 6 mg daily.1 If the toxicity recurs at a dosage of 6 mg daily, the dosage should be reduced to 3 mg daily.1 If patients are unable to tolerate the second dosage reduction, inavolisib should be permanently discontinued.1
Adverse Reaction | Dosage Modification Based on Severity |
|---|---|
Hyperglycemia | Fasting glucose levels (FPG or FBG) >ULN to 160 mg/dL: No adjustment required. Consider dietary modifications and ensure adequate hydration; initiate or intensify oral anti-hyperglycemic medications for patients with risk factors for hyperglycemia. Fasting glucose levels >160 to 250 mg/dL: Withhold until FPG or FBG ≤160 mg/dL; initiate or intensify anti-hyperglycemic medications. Resume inavolisib at the same dose level. If FPG or FBG persists >200-250 mg/dL for 7 days under the appropriate anti-hyperglycemic treatment, consider consultation with a healthcare professional experienced in hyperglycemia management. Fasting glucose levels >250 to 500 mg/dL: Withhold therapy. Initiate or intensify anti-hyperglycemic medications. Administer appropriate hydration if required. If FPG or FBG decreases to ≤160 mg/dL within 7 days, resume inavolisib at the same dose. If FPG or FBG decreases to ≤160 mg/dL in ≥8 days, resume at 1 lower dose level. If FPG or FBG >250 to 500 mg/dL recurs within 30 days, withhold until FPG or FBG decreases to ≤160 mg/dL, then resume at 1 lower dose level. Fasting glucose levels >500 mg/dL: Withhold therapy. Initiate or intensify anti-hyperglycemic medications. Assess for volume depletion and ketosis and administer appropriate hydration. If FPG or FBG decreases to ≤160 mg/dL, resume inavolisib at 1 lower dose level. If FPG or FBG >500 mg/dL recurs within 30 days, permanently discontinue therapy. |
Stomatitis | Grade 1: No adjustment necessary. Initiate or intensify appropriate medical therapy (e.g., corticosteroid-containing mouthwash) as clinically indicated. Grade 2: Withhold until improvement to grade 1 or lower. Initiate or intensify appropriate medical therapy. Resume inavolisib at the same dose level. For recurrent grade 2 stomatitis, withhold until recovery to grade 1 or lower, then resume at one lower dose level. Grade 3: Withhold until recovery to grade 1 or lower. Initiate or intensify appropriate medical therapy. Resume inavolisib at 1 lower dose level. Grade 4: Permanently discontinue therapy. |
Diarrhea | Grade 1: No adjustment required. Initiate appropriate medical therapy and monitor as clinically indicated. Grade 2: Withhold until recovery to grade 1 or lower, then resume inavolisib at same dose level. Initiate or intensify appropriate medical therapy and monitor as clinically indicated. For recurrent grade 2 diarrhea, withhold until recovery to grade 1 or lower, then resume inavolisib at one lower dose level. Grade 3: Withhold until recovery to grade 1 or lower, then resume inavolisib at one lower dose level. Initiate or intensify appropriate medical therapy and monitor as clinically indicated. Grade 4: Permanently discontinue therapy. |
Hematologic toxicities | Grade 1, 2, or 3: No adjustment required. Monitor CBC and for signs or symptoms of hematologic toxicities as clinically indicated. Grade 4: Withhold until recovery to grade 2 or lower. Resume inavolisib at the same dose level or reduce to one lower dose level as clinically indicated. |
Other adverse reactions | Grade 1: No adjustment required. Grade 2: Consider withholding, if clinically indicated, until recovery to grade 1 or lower. Resume inavolisib at the same dose level. Grade 3 (first event): Withhold until recovery to grade 1 or lower. Resume inavolisib at the same dose level or one lower dose level based on clinical evaluation. Grade 3 (recurrent): Withhold until recovery to grade 1 or lower. Resume inavolisib at one lower dose level. Grade 4: Permanently discontinue therapy. |
The manufacturer makes no specific dosage recommendation for patients with hepatic impairment.1
In patients with moderate renal impairment (eGFR 30 to <60 mL/min), the recommended starting dosage of inavolisib is 6 mg orally once daily.1
The manufacturer makes no specific dosage recommendations for geriatric patients.1
Inavolisib can cause severe or fatal hyperglycemia, including ketoacidosis.1 Ketoacidosis with a fatal outcome has occurred in the postmarketing setting.1
In patients receiving inavolisib, increased fasting blood glucose occurred in 85% of patients, including 22% of patients with Grade 2, 12% with Grade 3, and 0.6% with Grade 4 events.1 The median time to initial onset of hyperglycemia was 7 days (range 2-955 days).1 Hyperglycemia led to dose interruption in 28%, to dose reduction in 2.5%, and to discontinuation of inavolisib in 1.2% of patients.1
The safety of inavolisib in patients with Type 1 diabetes mellitus, or Type 2 diabetes mellitus requiring ongoing antihyperglycemic treatment, has not been studied.1
Prior to initiating treatment, evaluate fasting glucose levels and hemoglobin A1C (HbA1C), and optimize fasting glucose.1 After initiating therapy, or in patients who experience hyperglycemia during treatment, monitor or self-monitor fasting glucose levels once every 3 days for the first week, then once every week for the next 3 weeks, then once every 2 weeks for the next 8 weeks, then once every 4 weeks thereafter, and as clinically indicated.1 Monitor HbA1c every 3 months and as clinically indicated.1
Manage hyperglycemia with anti-hyperglycemic medications as clinically indicated.1 Monitor fasting blood glucose levels while on anti-hyperglycemic medications.1
Consider consultation with a healthcare professional experienced with hyperglycemia and monitoring patient's blood glucose levels at home for patients with risk factors for hyperglycemia or those who experience hyperglycemia.1 Advise patients of the signs and symptoms of hyperglycemia; counsel patients on lifestyle changes.1 Interrupt, reduce, or discontinue inavolisib based on hyperglycemia severity.1
Inavolisib can cause severe stomatitis.1 In patients receiving inavolisib in combination with palbociclib and fulvestrant, stomatitis was reported in 51% of patients, including Grade 3 events in 6% of patients.1 The median time to initial onset was 13 days (range 1-60 days).1 Stomatitis led to dose interruption in 10%, to dose reduction in 3.7%, and to discontinuation of inavolisib in 0.6% of patients.1
A mouthwash containing a corticosteroid was used in 38% of patients receiving inavolisib in combination with palbociclib and fulvestrant for the management or prophylaxis of stomatitis.1
Monitor patients for signs and symptoms of stomatitis.1 Interrupt, reduce, or discontinue inavolisib based on severity.1
Inavolisib can cause severe diarrhea, including dehydration and acute kidney injury.1 In patients receiving inavolisib in combination with palbociclib and fulvestrant, diarrhea was reported in 48% of patients, including Grade 3 events in 3.7% of patients.1 The median time to initial onset was 15 days (range 2-602 days).1 Antidiarrheal medications were used in 28% of patients receiving inavolisib in combination with palbociclib and fulvestrant for symptom management.1 Diarrhea led to dose interruption in 7% and dose reduction in 1.2% of patients.1
Monitor patients for signs and symptoms of diarrhea.1 Advise patients to increase oral fluids and start antidiarrheal treatment at the first sign of diarrhea.1 Interrupt, reduce, or discontinue inavolisib based on severity.1
Fetal/Neonatal Morbidity and Mortality
Based on findings of animal reproductive studies and its mechanism of action, inavolisib may cause embryo-fetal harm when administered to pregnant females.1 Oral administration of inavolisib to pregnant rats 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 once daily.1
Advise pregnant women and females of reproductive potential of the potential risk to a fetus.1 Advise females of reproductive potential to use effective non-hormonal contraception during treatment and for 1 week after the last dose.1 Advise male patients with female partners of reproductive potential to use effective contraception during treatment and for 1 week after the last dose.1
There are no adequate and well-controlled studies of inavolisib in pregnant women; however, based on findings of animal reproductive studies and its mechanism of action, inavolisib may cause embryo-fetal harm when administered to pregnant females.1
It is not known whether inavolisib is distributed into human milk, or if the drug has any effects on the breastfed infant or on milk production.1 Because of the potential for serious adverse reactions to inavolisib in nursing infants, advise patients to discontinue breastfeeding during and for 1 week after final dose.1
Females and Males of Reproductive Potential
Results of animal studies suggest that inavolisib may impair female and male fertility.1
Verify pregnancy status in females of reproductive potential prior to initiating treatment.1 Advise females of reproductive potential to use effective non-hormonal contraception during treatment and for 1 week after the last dose.1 Advise male patients with female partners of reproductive potential to use effective contraception during treatment and for 1 week after the last dose.1
Safety and efficacy of inavolisib have not been established in pediatric patients.1
In the INAVO120 study, 15% of patients were ≥65 years of age and 3% were ≥75 years of age.1 Patients ≥65 years of age in this study had a higher incidence of dosage modifications or interruptions of therapy due to adverse effects than younger patients (79 versus 68%).1 An insufficient number of patients ≥65 years of age were included in clinical studies to determine whether they respond differently from younger patients.1
No clinically significant differences in pharmacokinetics were observed in patients with mild hepatic impairment.1 Inavolisib has not been studied in patients with moderate and severe hepatic impairment.1
No clinically significant differences in pharmacokinetics were observed in patients with mild renal impairment.1 AUC was 73% higher in patients with moderate renal impairment compared to patients with normal renal function; dosage reduction is recommended in patients with moderate renal impairment.1 Safety and efficacy of inavolisib have not been established in patients with severe renal impairment.1
The most common adverse reactions (≥ 20%) including laboratory abnormalities, reported with inavolisib in clinical studies 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.1
In vitro studies indicate that inavolisib induces cytochrome P-450 (CYP) isoenzyme 3A and CYP2B6.1
Inavolisib is a time-dependent inhibitor of CYP3A.1 Inavolisib does not inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, or CYP2D6.1
Inavolisib is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), but is not a substrate of organic anion transporting polypeptide (OATP)1B1, OATP1B3, organic cation transporter (OCT)1, OCT2, multidrug and toxin extrusion transporter (MATE)1, MATE2K, or organic anion transporter (OAT)1, OAT2.1
Inavolisib does not inhibit P-gp, BCRP, OATP1B1, OATP1B3, OCT1, OCT2, OAT1, OAT3, MATE1, or MATE2K.1
Concomitant use of proton pump inhibitors (PPIs) and inavolisib did not have a clinically meaningful effect on inavolisib exposure.1, 3
Inavolisib is a highly selective small molecule inhibitor of the p110 catalytic subunit alpha isoform protein of phosphatidylinositol 3-kinase (PI3K).1, 2, 3 Activation of PI3K pathway activity is frequently observed in breast cancer, leading to uncontrolled tumor cell growth and drug resistance.7 In vitro, inavolisib induced the degradation of mutated PI3K catalytic alpha subunits p110α, inhibited phosphorylation of the downstream target protein kinase B (AKT), reduced cellular proliferation, and induced apoptosis in PIK3CA -mutated breast cancer cell lines.1, 3 In vivo, inavolisib reduced tumor growth in PIK3CA -mutated, estrogen receptor-positive, breast cancer xenograft models.1, 3 The anti-tumor activity was more pronounced when inavolisib was used in combination with fulvestrant and palbociclib.1, 3
The time course of pharmacodynamic response of inavolisib is unknown.1 Higher systemic exposure of inavolisib was associated with higher incidence of Grade 2 or higher anemia, Grade 2 or higher hyperglycemia, and inavolisib dosage modifications due to adverse reactions.1 Steady state concentrations are predicted to be reached by day 5.1 Inavolisib absolute oral bioavailability is 76% and steady state median time to maximum plasma concentration is 3 hours.1 A high fat meal did not have any clinically significant effects on the pharmacokinetics of inavolisib.1 Inavolisib is 37% plasma protein bound.1 The elimination half-life of the drug is 15 hours.1 Inavolisib is primarily metabolized by hydrolysis.1 Inavolisib is minimally metabolized by P-450 (CYP) isoenzyme 3A in vitro.1 Following oral administration of a single dose, 49% of the dose was recovered in urine and 48% in feces.1
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.
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.
Inavolisib is available through designated specialty pharmacies.6 Contact the manufacturer, Genentech, for more information.6
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Tablets, film-coated | 3 mg | Itovebi® | Genentech |
9 mg | Itovebi® | Genentech |
AHFS® Drug Information. © Copyright, 1959-2026, Selected Revisions January 10, 2026. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
Only references cited for selected revisions after 1984 are available electronically.
1. Genentech, Inc. Itovebi® (Inavolisib) ORAL prescribing information. 2025 Sept. [Web]
2. Turner NC, Im SA, Saura C, et al. Inavolisib-based therapy in PIK3CA-mutated advanced breast cancer. N Engl J Med. 2024;391(17):1584-1596.
3. US Food and Drug Administration. Center for Drug Evaluations and Research Application Number: 219249Orig1s000 Multi-Discipline Review. From FDA website. Accessed 2025 Apr 30.
5. ESMO. HR-positive, HER2-negative Metastatic Breast Cancer. Published 2025. Accessed May 6, 2025. [Web]
6. Genentech. Contact Us. [Web]
7. Ellis H, Ma CX. PI3K inhibitors in breast cancer therapy. Curr Oncol Rep. 2019;21(12):110.
26. Burstein HJ, DeMichele A, Fallowfield L, et al. Endocrine and targeted therapy for hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer-capivasertib-fulvestrant: ASCO rapid recommendation update. J Clin Oncol. 2024;42(12):1450-1453.