Inavolisib vs Alpelisib Plus Fulvestrant For Patients With PIK3CA-Mutated Advanced Breast Cancer

The Ongoing Phase 3 INAVO121 Trial

Demetria Smith-Graziani, MD, MPH, Winship Cancer Institute at Emory University, Nashville, Tennessee, describes the ongoing INAVO121 study. In this phase 3 trial, inavolisib plus fulvestrant is compared to alpelisib plus fulvestrant for the treatment of patients with PIK3CA-mutated, HR-positive, HER2-negative, locally advanced or metastatic breast cancer who progressed on or after treatment with a CDK4/6-inhibitor–based regiment.

Dr Smith-Graziani commented, “There are some difficulties with PI3-kinase inhibitors having certain toxicities…and so there have been attempts to try to find options that cause less side effects for patients and are better for their quality of life.”

Transcript:

Hi, I'm Demetra Smith Graziani. I'm an assistant professor and breast medical oncologist at Winship Cancer Institute of Emory University. I'm just going to be giving a brief overview of the INAVO-121 trial, which is a phase 3 trial that is currently in progress.

This trial is comparing the use of 2 different PI3-kinase inhibitors. One is a novel PI3-kinase inhibitor in inavolisib, and the other one is an already approved by the FDA, PI3-kinase inhibitor, alpelisib. This trial is comparing the use of both of them in combination with fulvestrant.

We have some data on the use of an inavolisib among patients with PI3-kinase–mutated, hormone receptor-positive, HER2-negative metastatic breast cancer. And as I mentioned, alpelisib is already approved in this population. There are some difficulties with PI3-kinase inhibitors having certain toxicities, specifically hyperglycemia, stomatitis, rash, and diarrhea. And so there have been attempts to try to find options that cause less side effects for patients and are better for their quality of life. It's thought that inavolisib might be a good option for that.

In this trial, which is currently enrolling and ongoing, they're looking at patients who have metastatic, hormone receptor-positive, HER2-negative breast cancer that have had progression either after the use of a CDK4/6 inhibitor or while still on a CDK4/6 inhibitor. Patients in the study are allowed to have received up to 2 prior lines of treatment in the metastatic setting, including up to 1 prior line of chemotherapy. In this study, they're going to have the primary end point as progression-free survival with a number of secondary end points, including overall survival, safety and tolerability, as well as patient-reported outcomes. They're going to be stratifying by a number of criteria, such as whether or not a patient has visceral disease or whether or not they received their CDK4/6 inhibitor in the adjuvant or the metastatic setting.

I'm very interested in seeing what the results of this trial will be. I think it's important because it may provide us with another option for patients with these PI3-kinase–mutated tumors. And it might be an option that potentially provides less toxicity compared to alpelisib, which can sometimes be difficult to maintain patients on due to issues with hyperglycemia and other side effects.

I'm really interested to see what the results are, and I think it is a good option for patients that fall into this population to consider as an alternative to standard of care.

Source:

Juric D, Kalinsky K, Im S-A, et al. INAVO121: Phase III study of inavolisib (INAVO) + fulvestrant (FUL) vs. alpelisib (ALP) + FUL in patients (pts) with hormone receptor-positive, HER2-negative (HR+, HER2–), PIK3CA-mutated (mut) locally advanced or metastatic breast cancer (LA/mBC). J Clin Oncol. 2024;42(16_suppl). doi: 10.1200/JCO.2024.42.16_sppl.TPS1136.