New findings from the phase III INAVO120 trial showed that adding inavolisib to palbociclib and fulvestrant may help extend survival and delay the time until treatment with chemotherapy in previously treated patients with PIK3CA-mutated, HR-positive, HER2-negative advanced breast cancer. The research was presented during a press briefing ahead of the 2025 ASCO Annual Meeting by Nicholas C. Turner, MD, PhD, FRCP, FMedSci, and colleagues (Abstract 1003).
“The INAVO120 study was designed to address a need for more potent and tolerable therapies for PIK3CA-mutated, HR-positive, HER2-negative advanced breast cancer in the first-line setting. The INAVO120 trial findings support an inavolisib-based regimen as an emerging new standard of care that helps people live longer, as well as substantially improving how long treatment works,” said lead study author Dr. Turner, of the Royal Marsden Hospital, London.
HR-positive, HER2-negative breast cancer is the most common subtype of breast cancer, accounting for about 70% of breast cancers in the United States. Previous research has found that about 40% of people with HR-positive, HER2-negative breast cancer have a mutation in the PIK3CA gene, which is often associated with a poor prognosis.
INAVO120
Inavolisib, a PI3K inhibitor, works by targeting the PIK3CA mutation, which can stop cancer cells from dividing and spreading. In 2024, the U.S. Food and Drug Administration (FDA) approved inavolisib in combination with palbociclib and fulvestrant to treat people with HR-positive, HER2-negative advanced breast cancer with a PIK3CA mutation that has grown after treatment with hormone therapy. Palbociclib is a targeted therapy that inhibits the activity of CDK4/6 enzymes, and fulvestrant is a hormonal therapy. The 2024 FDA approval was based on previous results from INAVO120, which found that progression-free survival significantly improved in patients who received inavolisib in combination with palbociclib and fulvestrant. In this INAVO120 update, researchers analyzed the final overall survival data.
Key Findings
INAVO120 included 325 patients with PIK3CA-mutated, HR-positive, HER2-negative locally advanced or metastatic breast cancer that had grown during or after treatment with hormone therapy. The patients were randomly assigned to receive either inavolisib in combination with palbociclib and fulvestrant (n = 161) or a placebo with palbociclib and fulvestrant (n = 164).
After a median follow-up of 34.2 months, researchers found the following results:
- The median overall survival was 34 months for patients in the inavolisib group vs 27 months for those in the placebo group.
- Overall, the inavolisib combination reduced the risk of death by 33%.
- For those who received inavolisib, the probability that they would still be alive after treatment was 96.8% at 6 months after treatment vs 90.1% in the placebo group; at 1 year, the rate was 87% vs 76.7%; at 1.5 years, 74.3% vs 67.2%; at 2 years, 65.8% vs 56.3%; and at 2.5 years, 56.5% vs 46.3%.
- The objective response rate was 62.7% for patients in the inavolisib group vs 28% in the placebo group.
- The median time until patients needed to start chemotherapy was 35.6 months in the inavolisib group vs 12.6 months in the placebo group.
- The median progression-free survival was recalculated from 15 months in the inavolisib group to 17.2 months, whereas the median progression-free survival remained 7.3 months in the placebo group.
Serious side effects were reported in most patients in both groups:
- A total of 7% of patients in the inavolisib group experienced a grade 3 or 4 adverse event compared with 84.7% of those in the placebo group.
- Hyperglycemia of any grade was particularly common in the inavolisib group (63.4% of patients vs 13.5% in the placebo group).
- A total of 8% of patients in the inavolisib group discontinued treatment because of side effects vs 0.6% in the placebo group.
Next Steps
Beyond INAVO120, inavolisib is currently being investigated in three other phase III studies: INAVO121, INAVO122, and INAVO123. All studies are in PIK3CA-mutated locally advanced or metastatic breast cancer using various treatment combinations.
ASCO Expert Perspective
“The INAVO120 trial has identified a targeted treatment regimen that meaningfully improves survival in patients with untreated PIK3CA-mutated, HR-positive, HER2-negative metastatic breast cancer—a big step forward for these patients. This study illustrates the importance of genomic testing at the time of diagnosis of HR-positive metastatic breast cancer, so that patients with PIK3CA mutations who qualify for this approach can be readily identified,” commented Jane Lowe Meisel, MD, FASCO, Co-Director, Breast Medical Oncology, at the Winship Cancer Institute of Emory University School of Medicine, and an ASCO expert in breast cancer.
Disclosure: This study was funded by F. Hoffmann–La Roche and a grant (P30CA008748) to the Memorial Sloan Kettering Cancer Center. For full disclosures of the study authors, visit coi.asco.org.
