FDA Approves Itovebi Combo for Some With Advanced Breast Cancer

The Food and Drug Administration (FDA) has approved Itovebi (inavolisib) with Ibrance (palbociclib) and Faslodex (fulvestrant) for certain patients with advanced or metastatic breast cancer.

Specifically, the Itovebi regimen is for the treatment of adult patients with endocrine-resistant, PIK3CA-mutated, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced or metastatic breast cancer. This is detected and determined by an FDA-approved test after patients have experienced recurrence on or after the completion of adjuvant endocrine therapy.

The agency also announced that it has approved the FoundationOne Liquid CDx assay as a companion diagnostic device to identify patients with breast cancer for treatment with Itovebi with Ibrance and Faslodex, according to a news release from the FDA.

The approval was based on the findings of the INAVO120 trial, which included 325 patients with endocrine-resistant, PIK3CA-mutated HR-positive, HER2-negative locally advanced or metastatic breast cancer who experienced disease progression during or within 12 months of completing adjuvant endocrine therapy and who had not received prior systemic therapy for locally advanced or metastatic disease.

Patients received 9 milligrams of Itovebi or placebo orally daily with 125 milligrams of oral Ibrance daily for 21 consecutive days followed by seven days off, and 500 milligrams of Faslodex on days 1 and 15 of cycle 1 and then day 1 of every 28-day cycle.

The median progression-free survival (the time a patient lives without their disease spreading or worsening) was 15 months in the Itovebi group and 7.3 months in the placebo group. The objective response rate (patients who responded partially or completely to treatment) was 58% in the Itovebi group and 25% in the placebo arm. The median duration of response was 18.4 months in the Itovebi group and 9.6 months in the placebo group.

The most common side effects experienced by at least 20% of patients included decreased neutrophils (a type of white blood cell), decreased hemoglobin, increased fasting glucose, decreased platelets, decreased lymphocytes, stomatitis (inflammation of the mouth and lips), diarrhea, decreased calcium, fatigue, decreased potassium, increased creatinine, increased ALT (enzyme in the liver), nausea, decreased sodium, decreased magnesium, rash, decreased appetite, COVID-19 infection and headache.

“The PI3K pathway plays a pivotal role in disease progression and has been challenging to target,” said Dr. Komal Jhaveri, 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 of the INAVO120 study, in a news release issued by Itovebi manufacturer Genentech. “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."

The PIK3CA mutation is present in approximately 40% of HR-positive breast cancers and is associated with tumor growth, disease progression and treatment resistance, according to the news release.

“We are thrilled by the approval of the Itovebi-based regimen, which is a huge step forward for advanced breast cancer patients with a PIK3CA mutation,” said Jean Sachs, CEO of Living Beyond Breast Cancer, in a statement included in the news release. “It remains critical that all patients have access to early, comprehensive biomarker testing so they can better understand what treatment options may be most beneficial for them and their tumor type.”

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