New findings from the phase 3 INAVO120 trial show that adding inavolisib to palbociclib and fulvestrant can help extend survival and delay the time until treatment with chemotherapy in patients with previously treated PIK3CA-mutated, HR-positive, HER2-negative advanced breast cancer.

The research will be presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, taking place May 30-June 3 in Chicago.

“The INAVO120 study was designed to address a need for more potent and tolerable therapies for PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor 2-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 Nicholas C. Turner, MD, PhD, Royal Marsden Hospital, London, United Kingdom.

Inavolisib is a type of targeted therapy drug called a PI3K inhibitor. It works by targeting the PIK3CA mutation, which can stop cancer cells from dividing and spreading. In 2024, the U.S. Food and Drug Administration 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 following treatment with hormone therapy. Palbociclib is a targeted therapy drug that inhibits the activity of CDK4/6 enzymes, and fulvestrant is a hormone therapy drug.  

This approval was based on previous results from this phase 3 INAVO120 clinical trial, which found that progression-free survival (PFS) significantly improved in patients who received inavolisib in combination with palbociclib and fulvestrant. In this INAVO120 update, researchers analysed the final overall survival (OS) 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 following treatment with hormone therapy. The patients were randomly assigned to receive either inavolisib in combination with palbociclib and fulvestrant (161 patients) or a placebo with palbociclib and fulvestrant (164 patients). 

After a median follow-up of just under 3 years (34.2 months), researchers found that:

• The median OS 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 participants. 
• 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) 

  • 87% at 1 year after treatment (vs. 76.7%) 

  • 74.3% at 1.5 years after treatment (vs. 67.2%) 

  • 65.8% at 2 years after treatment (vs. 56.3%) 

  • 56.5% at 2.5 years after treatment (vs. 46.3%). 

• The objective response rate – the percentage of patients whose tumours shrank by more than 30% in response to treatment – 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. 
• With the final results now in hand, the median PFS was recalculated from 15 months in the inavolisib group to 17.2 months while the median PFS remained 7.3 months in the placebo group. 

Serious side effects occurred in most patients in both groups:

• 90.7% of patients in the inavolisib group experienced a grade 3 or 4 adverse event compared to 84.7% of those in the placebo group.
• Hyperglycemia, or high blood sugar, of any grade was particularly common in the inavolisib group (63.4% of patients vs. 13.5% in the placebo group).
• 6.8% of patients in the inavolisib group discontinued treatment due to side effects vs. 0.6% in the placebo group, though discontinuation rates were generally low. 

Beyond INAVO120, inavolisib is currently being investigated in three other phase 3 studies: INAVO121, INAVO122, and INAVO123. All 3 studies are in PIK3CA-mutated locally advanced or metastatic breast cancer using various treatment combinations. 

Source: ASCO