FDA Approves Inavolisib with Palbociclib and Fulvestrant for Advanced Breast Cancer

On October 10, 2024, the FDA approved inavolisib (Itovebi, Genentech, Inc.) in combination with palbociclib and fulvestrant for adults with endocrine-resistant, PIK3CA-mutated, hormone receptor (HR)-positive, HER2-negative advanced breast cancer.

This approval targets patients with locally advanced or metastatic disease who have experienced recurrence after completing adjuvant endocrine therapy.

Efficacy was assessed in the INAVO120 trial (NCT04191499), a randomized study of 325 patients with endocrine-resistant, PIK3CA-mutated, HR-positive, HER2-negative advanced breast cancer. Participants had disease progression during or within 12 months of adjuvant therapy and no prior systemic treatment.

First-line inavolisib/placebo + palbociclib + fulvestrant (Inavo/Pbo+Palbo+Fulv) in patients (pts) with PIK3CA-mutated, hormone receptor-positive, HER2-negative locally advanced/metastatic breast cancer who relapsed during/within 12 months (mo) of adjuvant endocrine therapy completion: INAVO120 Phase III randomized trial additional analyses.

Authors: Dejan Juric, Kevin Kalinsky, Nicholas C. Turner, Komal L. Jhaveri, Peter Schmid, Sherene Loi, Cristina Saura, Seock-Ah Im, Patrapim Sunpaweravong, Huiping Li, Antonino Musolino, Qingyuan Zhang, Zbigniew Nowecki, Roland Ching-Yu Leung, Eirini Thanopoulou, Noopur Shankar, Guiyuan Lei, Jacob Devine, Thomas J Stout, and Sibylle Loibl

Patients received either inavolisib 9 mg or placebo, alongside palbociclib 125 mg daily for 21 days with 7 days off, and fulvestrant 500 mg on specified days. The median progression-free survival (PFS) was 15.0 months for inavolisib versus 7.3 months for placebo (Hazard ratio 0.43, p < 0.0001). The overall response rate (ORR) was 58% for inavolisib compared to 25% for placebo.

Common adverse reactions (≥20%) included decreased neutrophils, anemia, and diarrhea.

The recommended dose of inavolisib is 9 mg orally once daily until disease progression. The FDA also approved the FoundationOne Liquid CDx assay as a companion diagnostic.

This review was part of Project Orbis, facilitating concurrent regulatory review among international partners, including the TGA and Health Canada.

The principal investigator for the trial is Komal Jhaveri.

Komal Jhaveri is a prominent breast oncologist and early drug development specialist at Memorial Sloan Kettering (MSK) Cancer Center in New York. She serves as the section head of the Endocrine Therapy Research Program and the clinical director of the Early Drug Development Service, where she focuses on early-phase clinical trials for novel breast cancer therapies.

Dr. Jhaveri holds the Patricia and James Cayne Chair for Junior Faculty at MSK, reflecting her commitment to mentoring the next generation of oncologists. She earned her Doctor of Medicine (MD) from the University of Mumbai and completed her Internal Medicine residency there.

With numerous publications in leading medical journals, Dr. Jhaveri is dedicated to advancing treatment options and improving outcomes for patients with advanced breast cancer through innovative research and clinical practice.

Doctors and healthcare organisations shared their insights on social media.

Oncology Brothers:

“Inavolisib now FDA approved based off INAVO120: Ph III, Inavolisib (iPI3Ka) + Fulv + Palbo vs Palbo/Fulvestrant HR+ metastatic breast cancer:

– OS immature (favoring Inavo HR 0.64)
– PFS 15.0 vs 7.3mos (HR 0.43)
– AEs: and 50% hyperglycemia & stomatitis.”

MSK Department of Medicine:

“Breaking: The FDA approved inavolisib with palbociclib and fulvestrant for endocrine-resistant, PIK3CA-mutated, HR-positive, HER2-negative, advanced breast-cancer. Congrats to Komal Jhaveri.”

Paolo Tarantino:

“The triplet of inavolisib (PI3Kinh) and fulvestrant and palbocicilb is now approved for patients with PIK3CA-mut HR+/HER2- BC

When do you want to use this?

Patients with rapidly recurrent PIK3CA mutant disease (ie with recurrence on or shortly after adjuvant ET).”

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