FDA Approves Inavolisib, With Palbociclib and Fulvestrant, for Endocrine-Resistant, PIK3CA-Mutated, HR-Positive, HER2-Negative Advanced Breast Cancer

On October 10, 2024, the US Food and Drug Administration (FDA) approved inavolisib plus palbociclib and fulvestrant for patients with endocrine-resistant, PIK3CA-mutated, HR-positive, HER2-negative locally advanced or metastatic breast cancer, as detected by an FDA-approved test, who progressed on or after adjuvant endocrine therapy. In addition, the FDA approved the FoundationOne Liquid CDx assay as a companion diagnostic device to identify patients with breast cancer for this regimen.

This regulatory decision is based on results from the phase 3 INAVO120 study. This double-blind, placebo-controlled, multicenter trial enrolled 325 patients with endocrine-resistant, PIK3CA-mutated HR-positive, HER2-negative advanced breast cancer who progressed during or within 12 months of endocrine therapy and who had not received systemic therapy in this setting. Patients were randomized on a 1-to-1 basis to receive palbociclib plus fulvestrant, either with 9 mg inavolisib or placebo. The primary efficacy outcome measure was investigator-assessed progression-free survival (PFS). Additional efficacy measures included overall survival (OS), investigator-assessed objective response rate (ORR), and duration of response (DOR).

The media PFS in the inavolisib arm was 15.0 months vs 7.3 months in the placebo arm (hazard ratio [HR], 0.43; confidence interval [CI] 95%, 0.32 to 0.59; P < .0001). The ORR was 58% in the inavolisib arm and 25% in the placebo arm and the median DOR was 18.4 months and 9.6 months, respectively. According to an interim analysis of the OS (based on 63% of information), the fraction with inavolisib was not statistically significant, but was supportive of an overall benefit-risk assessment, with an HR of 0.64.

The most common adverse events occurring in ≥20% of patients, 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 ALT, nausea, decreased sodium, decreased magnesium, rash, decreased appeptite, COVID-19 infection, and headache.

The recommended dose of inavolisib is 9 mg taken orally once daily, with or without food.

Source:

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