FDA Approves Companion Diagnostic for Inavolisib in HR+/HER2–, PIK3CA-Mutated Breast Cancer

The FDA has approved FoundationOne CDx for use as a companion diagnostic for inavolisib (Itovebi) in combination with palbociclib (Ibrance) and fulvestrant (Faslodex) in the treatment of adult patients with endocrine-resistant, PIK3CA-mutated, hormone receptor–positive, HER2-negative, locally advanced or metastatic breast cancer.¹

Previously, the FDA approved the FoundationOne Liquid CDx for use as a companion diagnostic in the same indication in October 2024.^1,2

In October 2024, the regulatory agency approved inavolisib in combination with palbociclib and fulvestrant for the treatment of adult patients with endocrine-resistant, PIK3CA-mutated, hormone receptor–positive, HER2-negative, locally advanced or metastatic breast cancer, as detected by an FDA-approved test, following recurrence on or after completing adjuvant endocrine therapy.²

“The prevalence of PIK3CA mutations found in hormone receptor–positive, HER2-negative breast cancer makes it extremely important to have high quality, FDA-approved tests to match patients to the most effective therapy options in a timely manner,” Todd Druley, MD, PhD, chief medical officer at Foundation Medicine, stated in a news release.¹ “While actionable genomic alterations like PIK3CA may be identified by blood-based biopsy, some patients’ tumors may not be shedding adequate levels of tumor DNA into the blood for these alterations to be detected. In these cases, confirmatory tissue testing may help match more breast cancer patients to this therapy.”

What data supported the FDA approval of the inavolisib-based combination in hormone receptor–positive breast cancer?

The approval of inavolisib in combination with palbociclib and fulvestrant was based on findings from the phase 3 INAVO120 trial (NCT04191499).² Data from the study supporting the approval demonstrated that patients treated with inavolisib plus palbociclib and fulvestrant achieved a median progression-free survival (PFS) of 15.0 months (95% CI, 11.3-20.5) vs 7.3 months (95% CI, 5.6-9.3) for patients treated with placebo plus palbociclib and fulvestrant (HR, 0.43; 95% CI, 0.32-0.59; P < .0001).

The inavolisib-based combination also yielded an overall response rate (ORR) of 58% (95% CI, 50%-66%) compared with 25% (95% CI, 19%-32%) for the placebo-based treatment. The median durations of response (DOR) were 18.4 months (95% CI, 10.4-22.2) and 9.6 months (95% CI, 7.4-16.6), respectively.

An overall survival (OS) trend favoring the inavolisib regimen, based on a 63% information fraction, was observed (HR, 0.64; 95% CI, 0.43-0.97); although this difference did not reach statistical significance, the FDA noted at the time of approval that this trend supported the overall benefit:risk assessment.

How was the INAVO120 trial conducted?

INAVO120 was a randomized, double-blind, placebo-controlled study that enrolled patients at least 18 years of age with confirmed locally advanced or metastatic, hormone receptor–positive, HER2-negative breast cancer that was not amenable to curative-intent therapy.³ Patients were required to have disease progression during adjuvant endocrine therapy or within 12 months of completing adjuvant endocrine therapy. Confirmed PIK3CA-mutated disease was also necessary for inclusion.

Other key inclusion criteria comprised measurable disease per RECIST 1.1 criteria, an ECOG performance status of 0 or 1, a life expectancy of more than 6 months, and adequate hematologic and organ function.

Investigators excluded patients who had metaplastic breast cancer; had a history of leptomeningeal disease or carcinomatous meningitis; received any prior systemic therapy in the metastatic setting; had prior treatment with fulvestrant or any selective estrogen receptor degrader, unless given as part of neoadjuvant therapy lasting no longer than 6 months; had active or known/untreated central nervous system metastases; and received any prior treatment with a PI3K, AKT, or mTOR inhibitor.

Patients were randomly assigned 1:1 to receive inavolisib at 9 mg or placebo once per day on days 1 to 28 of each 28-day cycle in combination with palbociclib at 125 mg once per day on days 1 to 21 of each cycle and fulvestrant at 500 mg on days 1 and 15 of cycle 1, then on day 1 of subsequent cycles.¹ Treatment continued until disease progression or unacceptable toxicity.

PFS served as the trial’s primary end point. Secondary end points included ORR, best overall response, duration of response, clinical benefit rate, OS, quality of life, and safety.³

References

1. U.S. Food and Drug Administration approves FoundationOne CDx as a companion diagnostic for Itovebi (inavolisib) to identify patients with hormone receptor-positive, HER2-negative breast cancer with a PIK3CA mutation. News release. Foundation Medicine. June 2, 2026. Accessed June 4, 2026. https://www.foundationmedicine.com/press-release/fda-foundationone-cdx-itovebi
2. FDA approves inavolisib with palbociclib and fulvestrant for endocrine-resistant, PIK3CA-mutated, HR-positive, HER2-negative, advanced breast cancer. FDA. October 10, 2024. Accessed June 4, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-inavolisib-palbociclib-and-fulvestrant-endocrine-resistant-pik3ca-mutated-hr-positive
3. A study evaluating the efficacy and safety of inavolisib + palbociclib + fulvestrant vs placebo + palbociclib + fulvestrant in patients with PIK3CA-mutant, hormone receptor-positive, Her2-negative, locally advanced or metastatic breast cancer (INAVO120). ClinicalTrials.gov. Updated March 17, 2026. Accessed October 10, 2024. https://clinicaltrials.gov/ct2/show/NCT04191499