Who is this trial for?
This trial was for adults with a common type of advanced breast cancer that carries a specific mutation and had returned soon after finishing hormone treatment — a situation that tends to be harder to treat.
People in the trial had breast cancer that was:
- Hormone-receptor-positive, HER2-negative — the most common form of breast cancer, driven mainly by the hormone estrogen.
- Advanced (locally advanced or metastatic — spread beyond the breast).
- PIK3CA-mutated — carrying a change in the PIK3CA gene, which switches on an extra growth pathway.
- Quick to return — the cancer had come back during, or within 12 months of finishing, hormone therapy given after earlier surgery. This “endocrine-resistant” pattern signals a poorer prognosis.
What kind of trial is this?
This trial tested a new drug combination for treating advanced breast cancer that had become resistant to hormone therapy.
Background: why researchers asked this question
Hormone-receptor-positive breast cancer is usually treated by blocking estrogen. But cancers find ways around it. Doctors already combine hormone-blocking therapy with a CDK4/6 inhibitor (a drug that jams the cancer’s cell-division machinery) — a two-drug approach that works well for many people.
When a cancer also carries a PIK3CA mutation, it has a third growth route switched on. Researchers reasoned that blocking all three pathways at once — estrogen, cell division, and the PI3K pathway — might control the cancer better than blocking two. INAVO120 tested exactly that, in patients whose cancer had already shown it could resist hormone therapy.
The trial: what was tested and how
INAVO120 enrolled 325 people across 28 countries. They were randomly assigned to one of two groups:
- Inavolisib group (161 people): inavolisib plus palbociclib plus fulvestrant — all three drugs.
- Placebo group (164 people): a dummy pill plus palbociclib plus fulvestrant — the standard two-drug combination.
Neither the patients nor their doctors knew which group they were in (a “double-blind” design). The first goal was progression-free survival — how long people lived without the cancer growing. This report focused on the final overall survival results (how long people lived).
Results: what they found
Adding inavolisib improved every major measure — the cancer was held in check more than twice as long, more tumors shrank, and people lived longer.
Three drugs vs two drugs
The cancer was held in check for more than twice as long — the risk of it growing was cut by well over half (HR 0.42).
People lived about 7 months longer on average — a 33% lower risk of dying (HR 0.67). A survival gain of this size is uncommon in this hard-to-treat setting.
More than twice as many people saw their tumors shrink meaningfully.
The three-drug combination brought more side effects, as expected from adding a targeted drug. The most common were high blood sugar (hyperglycemia), mouth sores, diarrhea, and eye-related effects such as dry eye or blurred vision. Most were manageable: only 6.8% of people stopped inavolisib because of side effects. Low blood counts (from palbociclib) were common in both groups.
Why does inavolisib raise blood sugar?
The PI3K pathway that inavolisib blocks is the same pathway the body uses to respond to insulin and manage blood sugar. Blocking it in cancer cells also affects this normal process, so blood sugar can rise. This is expected, monitored with regular blood tests, and managed with diet, medication, and dose adjustments when needed.
The bottom line
For hormone-receptor-positive, HER2-negative advanced breast cancer with a PIK3CA mutation that returned quickly after hormone therapy, adding inavolisib to palbociclib and fulvestrant more than doubled the time without the cancer growing and extended overall survival by about 7 months. Blocking all three growth pathways at once worked better than blocking two — at the cost of more manageable side effects.
What this could mean for you
- It depends on a mutation test. This approach applies only to cancers with a PIK3CA mutation, which is found with a tumor or blood test. Ask your oncologist whether your cancer has been tested.
- The benefit was largest for a hard situation. These were cancers that had already resisted hormone therapy — a group with fewer good options.
- Side effects need monitoring. High blood sugar, mouth sores, and eye effects are expected and are managed with regular checks and dose adjustments.
Questions & comments
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