Dr Ansley on Inavolisib Plus Palbociclib/Fulvestrant in PIK3CA-Mutated HR+/HER2– Breast Cancer

"The phase 3 INAVO120 trial was an interesting study for patients who seemed to have very high-risk disease. It was actually a first-line study right now. Prior to this, we'd only been using PIK3CA inhibitors in the second line, but this study [involved] patients who had progressed during or within 12 months of stopping their adjuvant endocrine therapy."

Katherine C. Ansley, MD, an associate professor in the Section of Hematology and Oncology in the Department of Internal Medicine at Wake Forest University School of Medicine and a breast cancer leader at Atrium Health Wake Forest Baptist Hematology and Oncology - Cancer Center, discussed findings from the phase 3 INAVO120 trial (NCT04191499), which evaluated the addition of inavolisib (Itovebi) to palbociclib (Ibrance) and fulvestrant (Faslodex) in the first-line treatment of patients with endocrine-resistant, PIK3CA-mutated, hormone receptor (HR)–positive, HER2-negative advanced breast cancer.

Ansley noted that INAVO120 addressed a particularly high-risk population: patients whose disease recurred either during adjuvant endocrine therapy or within 12 months of completing it. Prior to this study, PIK3CA inhibitors had only been used in later-line settings. However, this trial moved the use of inavolisib into the first-line setting, reflecting a significant shift in treatment strategy for patients with aggressive disease biology.

Updated findings demonstrated a clinically meaningful improvement in progression-free survival (PFS) with the triplet combination. Patients who received inavolisib plus palbociclib and fulvestrant experienced a median PFS of 15.0 months (95% CI, 11.3-20.5), compared with 7.3 months (95% CI, 5.6-9.3) for those who received palbociclib and fulvestrant alone. The hazard ratio for disease progression or death was 0.43 (95% CI, 0.32-0.59; P < .0001), representing a 57% reduction in risk with the triplet regimen, Ansley explained.

These results supported the October 2024 FDA approval of inavolisib (Itovebi) paired with palbociclib (Ibrance) and fulvestrant (Faslodex) as a treatment for adult patients with endocrine-resistant, PIK3CA-mutated, hormone receptor–positive, HER2-negative, locally advanced or metastatic breast cancer after recurrence on or following completion of adjuvant endocrine therapy. Ansley concluded by emphasizing the significance of the approval, given the high-risk nature of this patient subset and the demonstrated efficacy of the targeted approach.