FDA Approves Itovebi as First-Line Therapy for PIK3CA-Mutated Breast Cancer

The US Food and Drug Administration (FDA) has approved Genentech’s Itovebi™ (inavolisib) as a targeted therapy for adults with advanced hormone receptor-positive, HER2-negative breast cancer harboring the PIK3CA mutation. This approval, based on the results from the Phase III INAVO120 trial, marks a significant advancement in the treatment of this challenging form of breast cancer.

Doubling Progression-Free Survival

The PIK3CA mutation, found in approximately 40% of HR-positive breast cancers, has been associated with a poor prognosis and resistance to standard endocrine therapies. According to the INAVO120 study, the Itovebi-based regimen, when combined with palbociclib (Ibrance®) and fulvestrant, more than doubled progression-free survival (PFS), significantly reducing the risk of disease worsening or death.

“The PI3K pathway plays a pivotal role in disease progression and has been challenging to target. The Itovebi-based regimen more than doubled progression-free survival and maintained a manageable safety and tolerability profile, adding a new standard in how PIK3CA-mutated breast cancers are treated,” said Dr. Komal Jhaveri, one of the principal investigators of the INAVO120 study.

The results were compelling: patients treated with the Itovebi regimen experienced a median PFS of 15 months compared to 7.3 months for those on palbociclib and fulvestrant alone. This marked a 57% reduction in disease progression risk (HR=0.43), highlighting the potential of Itovebi to shift the treatment landscape for these patients.

A New Standard in Care

“With the approval of this Itovebi-based regimen, we continue our long-standing track record of cancer therapeutic discovery by offering an important new first-line option for people living with HR-positive breast cancer with a PIK3CA mutation. Despite the high prevalence of PIK3CA mutations in this setting, treatment options have thus far remained limited, which makes today’s approval all the more significant,” said Dr. Levi Garraway, Genentech’s chief medical officer and head of Global Product Development.

While overall survival data from the INAVO120 trial is still maturing, initial results are promising. A positive trend in survival was observed, with further analysis expected in upcoming follow-up studies.

The FDA’s approval underscores the importance of early, comprehensive biomarker testing for patients with advanced breast cancer. Genentech emphasizes the necessity of using FDA-approved tests, such as Foundation Medicine’s FoundationOne® Liquid CDx, to identify patients with the PIK3CA mutation early in their treatment journey.

The Itovebi-based regimen was granted FDA Priority Review and Breakthrough Therapy Designation in May 2024 based on the INAVO120 study results. Data from INAVO120 are also being used for filing submissions to other global health authorities, including the European Medicines Agency. Itovebi is currently being investigated in various combinations across three company-sponsored Phase III clinical studies (INAVO120, INAVO121, INAVO122) in PIK3CA-mutated locally advanced or metastatic breast cancer.