FDA Approves Inavolisib in Locally Advanced, Metastatic Breast Cancer

The FDA announced the approval of inavolisib (Itovebi, Genentech, Inc.) to be used in patients who have locally advanced or metastatic breast cancer that is endocrine resistant, PIK3CA-mutated, hormone receptor (HR)-positive, and HER2-negative. The treatment can be given after recurrence either on or after completing adjuvant endocrine therapy.^1,2

The Phase 3 INAVO120 study provided the basis for the approval. The study was randomized, placebo-controlled, double-blind, and conducted through multiple centers to ultimately include 325 patients who had progression of their locally advanced or metastatic breast cancer during or within 12 months of completing their therapy. All patients also did not receive prior systemic therapy for their cancer. A relapse while on the first 2 years of adjuvant endocrine therapy (ET) was defined as primary endocrine resistance. Secondary endocrine resistance was defined as a relapse on ET after at least 2 years or a relapse within a year of completing adjuvant ET.

Patients were separated into 2 groups, with 1 group receiving inavolisib 9 mg and 1 group receiving a placebo; both were taken orally once per day. Both groups received palbociclib 125 mg orally once daily for 3 weeks and off of therapy for 1 week; they also received fulvestrant 500 mg on days 1 and 15 of the first cycle and then once per every 28 days. Unacceptable toxicity or disease progression marked the points when treatment was halted. Progression-free survival (PFS) was the main marker of efficacy for the treatment.

The median PFS was 15.0 months (95% CI, 11.3-20.5) in the group receiving inavolisib, compared with 7.3 (95% CI, 5.6-9.3) in the placebo group (HR, 0.43; 95% CI, 0.32-0.59). The objective response rate (ORR) was 58% (95% CI, 50%-66%) in patients taking the inavolisib compared with 25% (95% CI, 19%-32%) in the patients receiving a placebo. The median duration of response also significantly different, with those in the placebo arm having a median duration of 9.6 months (95% CI, 7.4-16.6) compared with 18.4 months (95% CI, 10.4-22.2).¹

Decreased neutrophils, increased fasting glucose, decreased hemoglobin, decreased lymphocytes, decreased platelets, diarrhea, fatigue, decreased calcium, stomatitis, increased creatinine, decreased sodium, decreased potassium, increased ALT, nausea, rash, decreased appetite, decreased magnesium, headache, and COVID-19 infection were all common adverse reactions, affecting at least 20% of the population.

The news of the FDA approval comes after it received FDA Priority Review and Breakthrough Therapy Designation in May of 2024. Inavolisib is also currently the focus of other phase 3 clinical studies in PIK3CA-mutated locally advanced or metastatic breast cancer.

“With the approval of this [inavolisib]-based regiment, 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,” Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development at Genentech, said in a press release.²

References

1. FDA approves inavolisib with palbociclib and fulvestrant for endocrine-resistant, PIK3CA-mutated, HR-positive, HER2-negative, advanced breast cancer. News release. FDA; October 10, 2024. Accessed October 11, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-inavolisib-palbociclib-and-fulvestrant-endocrine-resistant-pik3ca-mutated-hr-positive
2. FDA approves Genentech’s Itovebi, a targeted treatment for advanced hormone receptor-positive, HER2-negative breast cancer with a PIK3CA mutation. News release. Genentech; October 10, 2024. Accessed October 11, 2024. https://www.gene.com/media/press-releases/15039/2024-10-10/fda-approves-genentechs-itovebi-a-target