Adding Inavolisib to the Current Palbociclib-Fulvestrant Therapy to Treat Breast Cancer
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Reviewed & Translated by Dat Tien Nguyen, B.A, ScM.
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Posted on August 1st, 2025
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Hormone receptor-positive breast cancer has a complicated pathogenesis with different pathways influencing tumorigenesis. The 3 significant markers associated with disease include estrogen receptor, cyclin-dependent kinase 4 & 6 (CDK4/6), and phosphatidylinositol 3-kinase (PI3K). Of them, mutation to the latter, specifically the PIK3CA mutation is found in 40% of patients and is associated with worse prognosis. With funding from Roche, a study was conducted to investigate the addition of inavolisib to the current therapy to treat breast cancer.
The phase 3 clinical trial was conducted in 28 different countries and it included 161 participants with locally advanced or metastatic breast cancer. The trial included patients who had a tumor biopsy with PIK3CA mutation, with hormone receptor but without HER2 mutation. All of the patients were treated with the standard therapy of palbociclib 125 mg and fulvestrant 500 mg. Then, the participants were randomly assigned to be treated with either 9 mg of inavolisib or a placebo. Inavolisib works by binding to the mutated p110α catalytic subunit of the phosphatidylinositol 3-kinase enzyme. This interaction inhibits downstream growth and survival signals.
The researchers found that the addition of inavolisib to the standard palbociclib-fulvestrant combination significantly decreased the risk of death by 33% and increased average survival duration. Disease progression was observed more in patients treated only with the palbociclib-fulvestrant therapy. However, inavolisib usage is associated with a higher frequency and more severe adverse events that cause discontinuation in 6.8% of the patients, significantly more than the 0.6% observed in the placebo group. Ocular toxicity and gastrointestinal side effects were significantly more common in patients treated with inavolisib.
The phase 3 clinical trial was conducted in 28 different countries and it included 161 participants with locally advanced or metastatic breast cancer. The trial included patients who had a tumor biopsy with PIK3CA mutation, with hormone receptor but without HER2 mutation. All of the patients were treated with the standard therapy of palbociclib 125 mg and fulvestrant 500 mg. Then, the participants were randomly assigned to be treated with either 9 mg of inavolisib or a placebo. Inavolisib works by binding to the mutated p110α catalytic subunit of the phosphatidylinositol 3-kinase enzyme. This interaction inhibits downstream growth and survival signals.
The researchers found that the addition of inavolisib to the standard palbociclib-fulvestrant combination significantly decreased the risk of death by 33% and increased average survival duration. Disease progression was observed more in patients treated only with the palbociclib-fulvestrant therapy. However, inavolisib usage is associated with a higher frequency and more severe adverse events that cause discontinuation in 6.8% of the patients, significantly more than the 0.6% observed in the placebo group. Ocular toxicity and gastrointestinal side effects were significantly more common in patients treated with inavolisib.