Experimental Inavolisib Seems Promising for Certain Metastatic Breast Cancers
Inavolisib, a type of targeted therapy medicine called a PI3K inhibitor, in combination with Ibrance (chemical name: palbociclib), a CDK4/6 inhibitor, and Faslodex (chemical name: fulvestrant), more than doubled progression-free survival time compared to Ibrance and Faslodex alone in people diagnosed with advanced-stage, hormone receptor-positive, HER2-negative breast cancer with a PIK3CA mutation that had grown or come back (recurred) during or within 12 months of completing hormonal therapy treatment after surgery.
Advanced-stage breast cancer is either locally advanced or metastatic:
Locally advanced breast cancer has spread to tissue near the breast, but not to parts of the body away from the breast.
Metastatic breast cancer has spread to parts of the body away from the breast, such as the bones or liver.
Progression-free survival is how long a person lives without the cancer growing.
The research was presented on Dec. 8, 2023, at the San Antonio Breast Cancer Symposium.
Why do the study?
Up to 40% of hormone receptor-positive, HER2-negative breast cancers have a PIK3CA mutation. Currently, there is only one medicine, Piqray (chemical name: alpelisib), also a PI3K inhibitor, approved to treat breast cancer with this mutation.
PI3K inhibitors block the PI3K pathway. The PI3K pathway helps all cells — both healthy and cancer cells — get the energy they need. When this pathway is over-activated because of a mutation in the PIK3CA gene, it can allow cancer cells to survive and grow. PI3K inhibitors block this pathway, with the goal of killing cancer cells.
Different mutations in the PIK3CA gene make different forms of the PI3 protein, called isoforms by researchers. There are several isoforms of PI3; one of them is the alpha isoform. Piqray specifically targets the alpha isoform.
Because it targets the alpha isoform, Piqray can cause very high blood sugar levels, as well as severe skin reactions, including rashes and blisters.
Inavolisib also targets the alpha isoform, but in addition, it also damages mutant forms of the isoform. Researchers think this will make its side effects less severe than Piqray’s.
About the study
The study included 325 people diagnosed with advanced-stage, hormone receptor-positive, HER2-negative breast cancer with a PIK3CA mutation that had grown or recurred during treatment with hormonal therapy after surgery or within the 12 months after hormonal therapy was completed.
None of the people had received treatment for advanced-stage breast cancer.
The researchers randomly assigned the people to one of two treatment groups:
161 people received inavolisib, Ibrance, and Faslodex
164 people received a placebo — a pill that looked just inavolisib but contained no medicine — plus Ibrance and Faslodex
The people received the treatments until the cancer grew or until unacceptable side effects developed.
Median follow-up time was 21.3 months. This means that half the people were followed for a longer time and the other half were followed for a shorter time.
At median follow-up, progression-free survival was more than twice as long for people who received inavolisib with Ibrance and Faslodex, compared to people who received only Ibrance and Faslodex. Progression-free survival was:
15 months for people receiving inavolisib, Ibrance, and Faslodex
7.3 months for people receiving only Ibrance and Faslodex
This difference was statistically significant, which means that it was likely due to the difference in treatment and not just because of chance.
The information on overall survival — how long the people lived whether or not the cancer grew — was not ready to be analyzed yet, but there was a trend toward better overall survival in people who received inavolisib.
“Inavolisib in combination with palbociclib and fulvestrant may represent a new standard of care for patients with PIK3CA-mutated, hormone receptor-positive, HER2-negative advanced-stage breast cancer,” said Komal Jhaveri, MD, FACP, who presented the results. Dr. Jhaveri is a medical oncologist at Memorial Sloan Kettering Cancer Center, section head of the Endocrine Therapy Research Program, and clinical director of the Early Drug Development Service, and holds the Patricia and James Cayne Chair for Junior Faculty.
“I am very impressed with these results,” said Virginia Kaklamani, MD, professor of medicine in the Division of Hematology/Oncology at UT Health San Antonio, who moderated the media briefing where the results were presented. “Progression-free survival was more than doubled.”
The results suggest that the researchers’ hopes for inavolisib causing less severe side effects than Piqray were realized.
The most common side effects caused by inavolisib, occurring in more than 25% of people, were:
high blood sugar levels
And while mouth sores, high blood sugar levels, diarrhea, and rash were common side effects, they were not serious for most people:
5.6% of people had serious mouth sores
5.6% of people had serious high blood sugar levels
3.7% of people had serious diarrhea
none of the people had serious rash
Only about 7% of the people receiving inavolisib, Ibrance, and Faslodex stopped treatment because of side effects.
What this means for you
While these results are very promising, it’s important to know that inavolisib is not yet approved by the U.S. Food and Drug Administration.
It’s expected that Genentech, the company that makes inavolisib, will apply for approval, but it’s not clear when that will happen.
If you’ve been diagnosed with advanced-stage, hormone receptor-positive, HER2-negative breast cancer with a PIK3CA mutation and are deciding on treatments, you may want to talk to your doctor about this study and ask if a clinical trial on inavolisib makes sense for you.
Editor's Note: On Oct. 10, 2024, the U.S. Food and Drug Administration approved inavolisib (brand name: Itovebi) in combination with Ibrance (chemical name: palbociclib) and Faslodex (chemical name: fulvestrant) to treat advanced stage or metastatic hormone receptor-positive, HER2-negative breast cancer with a PIK3CA mutation. The cancer has to have grown during hormonal therapy treatment or come back after hormonal therapy ended.
Updated on July 3, 2025