FDA Approves Itovebi for Metastatic Breast Cancer

The FDA has Genentech’s new drug application for Itovebi (inavolisib) to treat adult patients with cally advanced or metastatic breast cancer. It is indicated for use in combination with Pfizer’s Ibrance (palbociclib) and fulvestrant to treat adult patients whose cancer has PIK3CA-mutation and is hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative.

At the same time, the FDA approved Foundations Medicine’s FoundationOneLiquid CDx to be used as a companion diagnostic for Itovebi.

Approximately 70% of all breast cancers are hormone-receptor positive, HER2-negative. PIK3CA is the most commonly mutated gene these cancers, with about 40% of patients having this mutation. But available inhibitors of PIK3 can have serious side effects, such as rash, infections, hypertension, hyperglycemia, liver disease and pneumonitis.

Itovebi is an oral targeted treatment that is designed to minimize the toxicity of other PI3K inhibitors. Itovebi will be available in the U.S. in the coming weeks at a cost of $22,867 for a 28-day cycle.

“The PI3K pathway plays a pivotal role in disease progression and has been challenging to target,” Komal Jhaveri, M.D., section head for the endocrine therapy research portfolio and clinical director of the early drug development service at Memorial Sloan Kettering Cancer Center, and one of the principal investigators, said in a news release.

The approval is based on data from the phase 3 INAVO120, which showed that the Itovebi based regimen more than doubled progression-free survival compared with palbociclib and fulvestrant alone in the first-line setting.

The Itovebi-based regimen reduced the risk of disease worsening or death by 57% compared with palbociclib and fulvestrant alone (15.0 months vs. 7.3 months. Overall survival (OS) data were immature at the time of primary analysis, but a clear positive trend was observed, according to Genentech officials.

The study enrolled 325 patients, who were randomly assigned to either the investigational or control treatment arm. The primary endpoint is progression-free survival, as assessed by investigators, defined as the time from randomization in the clinical trial to the time when the disease progresses, or a patient dies from any cause. Secondary endpoints include overall survival, objective response rate, and clinical benefit rate.

The most common grade 3-4 adverse effects with the inavolisib combination compared with palbociclib and fulvestrant alone were neutropenia, thrombocytopenia, anemia, stomatitis and hyperglycemia. The discontinuation rate in the inavolisib treatment group was 6.8% compared with 0.6% for palbociclib and fulvestrant alone.

Genentech is studying inavolisib in two additional company-sponsored phase 3 clinical studies (INAVO121, INAVO122) in PIK3CA-mutated locally advanced or metastatic breast cancer in various combinations.