FDA Approves Inavolisib Regimen for PIK3CA-mutated, HR+, HER2— Breast Cancer

The FDA approved inavolisib (Itovebi) plus palbociclib (Ibrance) and fulvestrant for the treatment of endocrine-resistant, PIK3CA-mutant, hormone-receptor (HR)-positive, HER2-negative locally advanced or metastatic breast cancer that is determined by an FDA-approved test. The indication is specifically for patients who experienced recurrence on or after adjuvant endocrine therapy.

The approval is based on findings from the randomized, double blind INAVO120 trial (NCT04191499), which included 325 patients whose disease progressed within 12 months of completing adjuvant endocrine therapy and who did not have prior systemic therapy for locally advanced or metastatic disease.

Researchers defined primary endocrine resistance as relapse within the first 2 years of adjuvant endocrine therapy, while secondary endocrine resistance was relapse while on adjuvant endocrine therapy after 2 or more years or relapse within 12 months of completing endocrine therapy.

Patients were randomly assigned 1:1 to receive an oral dose of either 9 mg of inavolisib or a placebo once per day, alongside 125 mg of daily palbociclib and 500 mg of fulvestrant administered on days 1 and 15 during cycle 1, followed by day 1 of every 28-day cycle thereafter. Participants continued treatment until disease progression or unacceptable toxicity.

The primary end point of the trial was progression-free survival (PFS) per RECIST version 1.1. Median PFS was 15.0 months (95% CI, 11.3-20.5) in the inavolisib arm and 7.3 months (95% CI, 5.6-9.3) in the placebo arm (hazard ratio, 0.43; 95% CI, 0.32-0.59; P < .0001).

Secondary end points were overall survival (OS), investigator-assessed objective response rate (ORR), and duration of response (DOR).

Median DORs were 18.4 months (95% CI, 10.4-22.2) and 9.6 months (95% CI, 7.4-16.6), respectively. Meanwhile, the ORR was 58% (95% CI, 50%-66%) in the inavolisib-containing arm and 25% (95% CI, 19%-32%) in the placebo arm.

An interim analysis of OS did not reach statistical significance but was supportive of the overall benefit risk assessment with the addition of inavolisib, reducing the risk for death by 36% (hazard ratio, 0.64; 95% CI, 0.43-0.97).

The most common adverse events (including laboratory abnormalities) that occurred in 20% or more of patients 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.

Reference

FDA news release. FDA approves inavolisib with palbociclib and fulvestrant for endocrine-resistant, PIK3CA-mutated, HR-positive, HER2-negative, advanced breast cancer. October 10, 2024. Accessed October 10, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-inavolisib-palbociclib-and-fulvestrant-endocrine-resistant-pik3ca-mutated-hr-positive