Inavolisib is an oral, selective inhibitor of phosphatidylinositol 3-kinase alpha (PI3Kα).
It is indicated for the treatment of adults with endocrine-resistant, PIK3CA-mutated, hormone receptor (HR)-positive, HER2-negative, locally advanced or metastatic breast cancer.
It is administered in combination with palbociclib and fulvestrant, and patient selection is based on the presence of PIK3CA mutations in plasma specimens.
The recommended dosage is 9 mg orally once daily, with dose adjustments for moderate renal impairment.
Inavolisib induces degradation of the mutated PI3K catalytic alpha subunit (p110α), inhibits downstream AKT phosphorylation, reduces cellular proliferation, and induces apoptosis in PIK3CA-mutated breast cancer cell lines.
Inavolisib has been characterized as a highly potent, oral, and selective inhibitor of the PI3Kα isoform, with unique activity in promoting the degradation of mutant p110α, the catalytic subunit encoded by PIK3CA.
This dual mechanism of selective inhibition and targeted degradation—distinguishes inavolisib from earlier PI3K inhibitors and promotes its clinical activity in PIK3CA-mutated, hormone receptor–positive, HER2-negative advanced breast cancer.
Clinical trials have demonstrated that inavolisib, when combined with palbociclib and fulvestrant, significantly improves progression-free survival and objective response rates compared to standard regimens in the first-line setting for endocrine-resistant, PIK3CA-mutated, HR-positive, HER2-negative advanced breast cancer.
The INAVO120 phase 3 trial reported a median progression-free survival of 15.0 months for the inavolisib combination versus 7.3 months for placebo, with manageable toxicity and a low rate of treatment discontinuation due to adverse events.
The most common grade 3–4 adverse events include neutropenia, hyperglycemia, and stomatitis, consistent with the class effects of PI3K inhibition, but the overall safety profile is considered acceptable.
A highly potent and selective inhibitor of the alpha isoform of the p110 catalytic sub unit of the PI 3K complex.
The FDA FoundationOne Liquid CDx assay can identify patients who qualify for the newly approved treatment.
A first-line option for people living with HR+ breast cancer with a PIK3CA mutation.
The oncogenic PIK3CA mutation is found in approximately 40% HR+ metastatic breast cancers.
Novartis’ alpelisib (Piqray) also targets the mutation and carries a similar breast cancer indication for combination with fulvestrant.
Approval of inavolisib was based on the INAVO120 trial, which randomized 325 qualifying patients equally to receive either inavolisib 9 mg or placebo orally once daily on a background of palbociclib and fulvestrant in 28-day treatment cycles.
In the INAVO120 study, patients taking inavolisib had a median progression-free survival of 15 months, compared to 7.3 months for those taking a placebo.
The overall response rate was also higher for patients taking inavolisib.
Common side effects include decreased neutrophils, increased fasting glucose, and fatigue.
In patients with PIK3CA mutated hormone receptor positive, HER2 negative locally advanced or metastatic breast cancer inavolisib plus palbociclib-fulvestrant led to longer progression free survival than placebo plus palbociclib-fulvestrant with a greater incidence of toxic effects.