Research Summary · Oncology

FDA Approves Inavolisib for PIK3CA‑Mutant HR+ HER2− Breast Cancer: Cuts Progression Risk 57% in INAVO120

September 08, 2026

FDA approval date

October 10, 2024

Primary trial

INAVO120 (NCT04191499)

Median PFS

15.0 months vs 7.3 months

Hazard ratio (PFS)

HR 0.43 (95% CI: 0.32-0.59)

Objective response rate

58% vs 25%

Recommended dose (inavolisib)

9 mg orally once daily

Clinical Perspective

This affects healthcare professionals responsible for treating adults with endocrine‑resistant, PIK3CA‑mutated, HR‑positive, HER2‑negative locally advanced or metastatic breast cancer who must select patients using an FDA‑approved test. The INAVO120 results and FDA approval support using inavolisib 9 mg orally once daily in combination with palbociclib and fulvestrant in the indicated patient population, with required patient selection by PIK3CA mutation testing and specified monitoring and dose‑modification strategies for adverse reactions. Will mature overall survival data and longer follow‑up confirm an overall survival benefit and clarify long‑term tolerability profiles?

Dr. Rahul Verma, MBBS, MD (General Medicine), DM (Medical Oncology) · Oncology

The FDA approved inavolisib (Itovebi) with palbociclib and fulvestrant for adults with endocrine‑resistant, PIK3CA‑mutated, hormone receptor (HR)‑positive, HER2‑negative, locally advanced or metastatic breast cancer on October 10, 2024, based on the randomized INAVO120 trial that showed a median investigator‑assessed progression‑free survival (PFS) of 15.0 months versus 7.3 months (HR 0.43; 95% CI: 0.32–0.59) versus placebo plus palbociclib and fulvestrant ^[3]^[6].

Clinical Context

INAVO120 enrolled patients with endocrine‑resistant, PIK3CA‑mutated, HR‑positive, HER2‑negative locally advanced or metastatic breast cancer whose disease progressed during or within 12 months of completing adjuvant endocrine therapy and who had not received prior systemic therapy for locally advanced or metastatic disease ^[6]. The approval is accompanied by a companion diagnostic, the FoundationOne Liquid CDx assay, to identify PIK3CA mutations for patient selection as required by the label and FDA announcement ^[3]^[6]. The inavolisib label describes patient selection based on one or more PIK3CA mutations in plasma specimens and provides recommended monitoring and dose modification guidance for adverse reactions, including hyperglycemia, stomatitis, and diarrhea ^[1]^[6]. Roche and the NEJM‑published phase III report framed the PFS improvement as reduction in the risk of disease worsening or death by 57% versus the control arm in INAVO120 ^[4]^[3].

Key Findings

INAVO120 (randomized, double‑blind, placebo‑controlled) showed that inavolisib plus palbociclib and fulvestrant reduced the risk of progression or death by 57% versus placebo plus palbociclib and fulvestrant (HR 0.43; 95% CI: 0.32–0.59) with median investigator‑assessed PFS 15.0 months versus 7.3 months ^[6]^[3].
Confirmed objective response rate (ORR) was 58% (95% CI: 50, 66) in the inavolisib arm versus 25% (95% CI: 19, 32) in the placebo arm, and median duration of response (DOR) was 18.4 months versus 9.6 months, respectively ^[3]^[6].
Interim overall survival (OS) analysis (based on an interim information fraction) did not reach the prespecified boundary for statistical significance but showed a favorable point estimate with HR 0.64 (95% CI: 0.43–0.97) reported in regulatory and peer‑reviewed summaries; follow‑up for OS will continue ^[3]^[5]^[6].
The FDA concurrently approved the FoundationOne Liquid CDx assay as the companion diagnostic to identify patients with PIK3CA‑mutated disease for treatment eligibility ^[3].

Safety & Tolerability

The prescribing information and FDA materials list the most common adverse reactions (≥20%) observed with inavolisib in combination with palbociclib and fulvestrant, including 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]^[2]^[3]. Increased fasting glucose occurred in 85% of patients treated with inavolisib, including 22% 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); hyperglycemia led to dose interruption in 28%, dose reduction in 2.5%, and discontinuation in 1.2% of patients in INAVO120 ^[1]^[2]^[6]. Clinicians should consult current prescribing information for full dosing guidance. Stomatitis occurred in 51% of patients (Grade 3 in 6%), with a median time to first onset of 13 days and led to dose interruption in 10% and dose reduction in 3.7% ^[1]^[2]. Diarrhea occurred in 48% of patients (Grade 3 in 3.7%) with median time to first onset of 15 days ^[1]^[2]. The label provides detailed dose‑modification tables and monitoring recommendations for hyperglycemia, stomatitis, diarrhea, and other adverse reactions ^[1]^[2].

Study Design

INAVO120 (NCT04191499) was a randomized (1:1), double‑blind, placebo‑controlled, multicenter phase III trial that enrolled 325 patients with endocrine‑resistant, PIK3CA‑mutated, HR‑positive, HER2‑negative locally advanced or metastatic breast cancer who had disease progression during or within 12 months of completing adjuvant endocrine therapy and had not received prior systemic therapy for locally advanced or metastatic disease ^[6]^[3]. Randomization was stratified by presence of visceral disease (yes/no), endocrine resistance (primary/secondary), and geographic region (North America/Western Europe, Asia, other) ^[6]. Patients received inavolisib 9 mg once daily or placebo, each in combination with palbociclib 125 mg orally once daily (21 days on, 7 days off per 28‑day cycle) and fulvestrant 500 mg IM on Cycle 1 Days 1 and 15 and then Day 1 of every 28‑day cycle; treatment continued until disease progression or unacceptable toxicity ^[6]^[3]. Clinicians should consult current prescribing information for full dosing guidance. The prespecified primary endpoint was investigator‑assessed progression‑free survival per RECIST v1.1; secondary endpoints included overall survival, investigator‑assessed ORR, and DOR ^[6]. Full eligibility criteria required HbA1C < 6% and fasting blood glucose < 126 mg/dL at baseline, and excluded patients with Type 1 diabetes mellitus or Type 2 diabetes mellitus requiring ongoing anti‑hyperglycemic treatment at study entry ^[6].

FAQ

Q1 What is inavolisib (Itovebi) approved for?

Inavolisib (Itovebi) is approved 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. The approval and indication are described in the FDA announcement and the prescribing information.

Q2 How does inavolisib work?

Inavolisib is a PI3K inhibitor with inhibitory activity predominantly against PI3Kα; in vitro it induced degradation of mutated PI3K catalytic alpha subunit p110α (encoded by PIK3CA), inhibited phosphorylation of downstream AKT, reduced cellular proliferation, and induced apoptosis in PIK3CA‑mutated breast cancer cell lines. The label also reports that in vivo models showed reduced tumor growth in PIK3CA‑mutated, estrogen receptor‑positive xenografts and that combination with palbociclib and fulvestrant increased tumor growth inhibition versus single or doublet therapy.

Q3 What is the recommended dose of inavolisib?

The recommended dosage of inavolisib (Itovebi) is 9 mg taken orally once daily with or without food until disease progression or unacceptable toxicity. The FDA label specifies administering inavolisib in combination with palbociclib (recommended dosage 125 mg orally once daily, 21 days on/7 days off per 28‑day cycle) and fulvestrant (500 mg IM on Days 1 and 15 of Cycle 1, then Day 1 of each 28‑day cycle), and provides dose‑reduction steps and specific guidance for renal impairment and for management of adverse reactions.

Q4 What are the most common side effects of inavolisib in combination with palbociclib and fulvestrant?

The most common adverse reactions (incidence ≥20%) include 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. The label highlights hyperglycemia as frequent (increased fasting glucose in 85% of patients in INAVO120, including Grade 2–4 events) and provides monitoring schedules and management recommendations. For full safety details and dose‑modification tables, consult the full prescribing information.

FDA Approves Inavolisib for PIK3CA‑Mutant HR+ HER2− Breast Cancer: Cuts Progression Risk 57% in INAVO120

Direct Clinical Takeaway & Evidence Summary

FDA Approves Inavolisib for PIK3CA‑Mutant HR+ HER2− Breast Cancer: Cuts Progression Risk 57% in INAVO120

Clinical Perspective

Clinical Context

Key Findings

Safety & Tolerability

Study Design

FAQ

References

Cite & Reference This Monograph

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