From the FDA Drug Label
- 1 Mechanism of Action Inavolisib is an inhibitor of phosphatidylinositol 3-kinase (PI3K) with inhibitory activity predominantly against PI3Kα In vitro, inavolisib induced the degradation of mutated PI3K catalytic alpha subunit p110α (encoded by the PIK3CA gene), inhibited phosphorylation of the downstream target AKT, reduced cellular proliferation, and induced apoptosis in PIK3CA-mutated breast cancer cell lines. In vivo, inavolisib reduced tumor growth in PIK3CA-mutated, estrogen receptor-positive, breast cancer xenograft models The combination of inavolisib with palbociclib and fulvestrant increased tumor growth inhibition compared to each treatment alone or the doublet combinations.
The current indications for Inavolisib (SAR245409, XL147) are for the treatment of breast cancer, specifically PIK3CA-mutated, estrogen receptor-positive breast cancer 1.
- Key points:
- Inavolisib is a PI3K inhibitor with activity against PI3Kα.
- It has shown efficacy in reducing tumor growth in PIK3CA-mutated breast cancer models.
- The combination of inavolisib with other therapies (palbociclib and fulvestrant) has shown increased tumor growth inhibition.
From the Research
Inavolisib is currently indicated for the treatment of hormone receptor-positive (HR+), HER2-negative, PIK3CA-mutated advanced or metastatic breast cancer in adult patients, in combination with palbociclib and fulvestrant, after disease progression following at least one line of endocrine therapy, as supported by the most recent evidence from 2.
Key Points
- The FDA approved this indication in October 2024, as reported in 2.
- The typical dosing is not explicitly stated in the most recent and highest quality study, but based on the available evidence, patients must have confirmed PIK3CA mutations before starting treatment.
- Common side effects include hyperglycemia, diarrhea, rash, and stomatitis, so regular monitoring of blood glucose levels is essential, particularly in patients with diabetes, as seen in 3.
- Inavolisib works by selectively inhibiting the PI3K-alpha isoform, which is often abnormally activated in breast cancers with PIK3CA mutations, leading to uncontrolled cell growth and proliferation.
- By blocking this pathway, inavolisib helps overcome resistance to endocrine therapy and improves progression-free survival in these patients, as demonstrated in 3.
Important Considerations
- The most recent study 2 provides the strongest evidence for the current indications of inavolisib.
- The study 3 provides additional information on the efficacy and safety of inavolisib in combination with palbociclib and fulvestrant.
- Other studies, such as 4, 5, and 6, provide preclinical and clinical data on inavolisib, but are not as relevant to the current indications as the most recent study 2.