Inavolisib (Itovebi) — Clinical FAQs

Question 1

What is Inavolisib FDA-approved to treat?

Accepted Answer

Inavolisib is FDA-approved for the following oncology indications: 1. PIK3CA-mutated, hormone receptor-positive (HR+), HER2-negative, endocrine-resistant, locally advanced or metastatic breast cancer — in combination with palbociclib and fulvestrant (approved October 2024, based on INAVO120).

Question 2

How does Inavolisib work (mechanism of action)?

Accepted Answer

Highly selective PI3Kα inhibitor with a dual mechanism of action — catalytic inhibition of the p110α subunit of PI3Kα combined with selective degradation of mutant p110α protein via the ubiquitin-proteasome pathway (a "degrader-inhibitor" mechanism). This dual action achieves deeper and more durable PI3Kα pathway suppression than catalytic inhibition alone. High isoform selectivity (α >> β, δ, γ) reduces hyperinsulinemia and hyperglycemia relative to less selective PI3K inhibitors. Active specifically in tumors harboring PIK3CA-activating mutations.

Question 3

How is Inavolisib administered?

Accepted Answer

Inavolisib is administered Oral (PO). Inavolisib 9 mg orally once daily on days 1–28 of each 28-day cycle, in combination with palbociclib 125 mg PO once daily on days 1–21 and fulvestrant 500 mg IM on days 1 and 15 of cycle 1, then day 1 of each subsequent cycle.

Question 4

What are the most common side effects of Inavolisib?

Accepted Answer

The most commonly reported side effects of Inavolisib (≥10% incidence) include: Hyperglycemia (79%, grade ≥3: 33%), Stomatitis / oral mucositis (68%, grade ≥3: 5%), Diarrhea (45%), Nausea (34%), Fatigue (33%) and others (10 total). Consult your oncologist for complete prescribing information.

Question 5

Does Inavolisib have a black box warning?

Accepted Answer

Yes. Inavolisib carries FDA black box warning(s) regarding: 1. Hyperglycemia and ketoacidosis: Inavolisib can cause severe or life-threatening hyperglycemia, including diabetic ketoacidosis. Optimize glycemic control before initiation; do not initiate in patients with fasting plasma glucose ≥126 mg/dL or HbA1c ≥7% that cannot be adequately controlled. Monitor fasting glucose and HbA1c frequently. Initiate antidiabetic treatment as clinically indicated and manage with dose modifications per labeling. Fatal hyperglycemic events have been reported. 2. Embryo-fetal toxicity: Inavolisib can cause fetal harm. Advise females of reproductive potential to use effective non-hormonal contraception during treatment and for 1 week after the last dose.

Question 6

Is Inavolisib safe during pregnancy?

Accepted Answer

Inavolisib pregnancy safety: Can cause fetal harm (no traditional FDA letter category per current labeling). PI3K pathway signaling is essential for normal embryonic development. Females of reproductive potential must use effective non-hormonal contraception during treatment and for 1 week after the last dose. Palbociclib co-administration carries an additional requirement: contraception for ≥3 weeks after palbociclib completion. Breastfeeding is not recommended during and for 1 week after inavolisib. Male patients with female partners of reproductive potential should use contraception during treatment.. Oncologists should review the complete prescribing information and discuss reproductive risks with patients before initiating therapy.

Inavolisib — Drug Monograph

Mechanism of Action

FDA Indications

Common Side Effects

Clinical Pearl

Related Therapies & Mechanisms