The randomized, double-blind, placebo-controlled trial enrolled 325 adult patients with endocrine resistant, PIK3CA-mutated, hormone receptor–positive, HER2-negative breast cancer that was locally advanced or metastatic.2 Patients were required to have experienced disease progression during or within 12 months of completing adjuvant endocrine therapy. Prior receipt of systemic therapy for locally advanced or metastatic disease was not permitted.

Upon enrollment, patients were randomly assigned 1:1 to receive either 9 mg of oral inavolisib or placebo once daily during a 28-day cycle. This was administered alongside 125 mg of daily palbociclib for 21 days per cycle and 500 mg of fulvestrant administered intramuscularly on days 1 and 15 of cycle 1, and day 1 of each subsequent cycle. Treatment continued until disease progression or unacceptable toxicity.

Stratification factors included the presence of visceral disease (yes vs no), endocrine resistance (primary vs secondary), and geographic region (North America/Western Europe vs Asia vs other).

The study’s primary end point was investigator-assessed PFS per RECIST 1.1 criteria. Secondary efficacy end points comprised OS, investigator-assessed ORR, and DOR.

The most common adverse effects reported in at least 20% of patients treated with the inavolisib-based regimen were decreased neutrophils, decreased hemoglobin, increased fasting glucose, decreased platelets, decreased lymphocytes, stomatitis, diarrhea, decreased calcium, fatigue, decreased potassium, increased creatinine, increased alanine aminotransferase levels, nausea, decreased sodium, decreased magnesium, rash, decreased appetite, COVID-19 infection, and headache. In the updated OS analysis, no new safety signals were observed.

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In addition to INAVO120, 3 phase 3 trials evaluating inavolisib-based combinations in patients with PIK3CA-mutated locally advanced or metastatic breast cancer are being conducted.1

These include the INAVO121 trial (NCT05646862), which is evaluating the agent in combination with fulvestrant vs alpelisib (Piqray) plus fulvestrant in hormone receptor–positive, HER2-negative breast cancer following progression on a CDK4/6 inhibitor and endocrine therapy; the INAVO122 study (NCT05894239) investigating inavolisib plus a subcutaneous fixed dose of pertuzumab (Perjeta) and trastuzumab (Herceptin) as maintenance therapy in HER2-positive disease; and the INAVO123 study (NCT06790693) evaluating first-line inavolisib plus a CDK4/6 inhibitor and letrozole in endocrine-sensitive, PIK3CA-mutated hormone receptor–positive, HER2-negative breast cancer.