Inavolisib Combination Therapy Approved by FDA for Advanced Breast Cancer Subtype

By: JNCCN 360 Staff
Posted: Friday, October 11, 2024

Yesterday, the U.S. Food and Drug Administration (FDA) approved the PI3K inhibitor inavolisib (Itovebi) with the CDK4/6 inhibitor palbociclib and fulvestrant for adults with endocrine-resistant, PIK3CA-mutated, hormone receptor (HR)-positive, HER2-negative, locally advanced or metastatic breast cancer, as detected by an FDA-approved test, following recurrence on or after completion of adjuvant endocrine therapy. The FDA also approved the FoundationOne Liquid CDx assay as a companion diagnostic device to identify patients with breast cancer for treatment with this combination therapy.

Efficacy was evaluated in INAVO120 (ClinicalTrials.gov identifier NCT04191499), a randomized, double-blind, placebo-controlled, multicenter trial in 325 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. Patients were randomly assigned 1:1 to receive either inavolisib at 9 mg or placebo orally once daily, with palbociclib at 125 mg orally once daily for 21 consecutive days followed by 7 days off treatment to constitute a cycle of 28 days, and fulvestrant at 500 mg administered intramuscularly on cycle 1, days 1 and 15, and then on day 1 of every 28-day cycle.

Median progression-free survival (the major efficacy outcome measure) was 15.0 months (95% confidence interval [CI] = 11.3–20.5 months) with inavolisib plus palbociclib and fulvestrant and 7.3 months (95% CI = 5.6–9.3 months) with placebo plus palbociclib and fulvestrant (hazard ratio = 0.43 [95% CI = 0.32–0.59] P < .0001). The objective response rate was 58% (95% CI = 50%–66%) with inavolisib and 25% (95% CI = 19%–32%) without it. The median duration of response was 18.4 months (95% CI = 10.4–22.2 months) and 9.6 months (95% CI = 7.4–16.6 months), respectively. Interim analysis of overall survival based on 63% information fraction did not reach statistical significance but was supportive of the overall benefit risk assessment, with a hazard ratio of 0.64 (95% CI = 0.43–0.97).

The most common adverse reactions (≥ 20%), 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 alanine transaminase, nausea, decreased sodium, decreased magnesium, rash, decreased appetite, COVID-19 infection, and headache.

The recommended inavolisib dose is 9 mg taken orally once daily, with or without food, until disease progression or unacceptable toxicity. Refer to the prescribing information for palbociclib and fulvestrant dosing information.

U.S. Food and Drug Administration

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