Inavolisib

Recent advancements in sequencing targeted therapies are reshaping HR-positive, HER2-negative metastatic breast cancer management, emphasizing the critical role of NGS in personalizing treatment decisions. Key factors include considering CDK 4/6 inhibitors, biomarker assessment, and sequencing new therapies like inavolisib and capivasertib. Trials such as SOLAR-1, INAVO120, and CAPItello-291 highlight improved progression-free survival and tolerable adverse effects. NGS is crucial for identifying PIK3CA/AKT mutations to determine optimal frontline and second-line treatments.

The 2024 NCCN Breast Cancer guidelines update includes ribociclib plus an aromatase inhibitor as a preferred regimen for HR-positive, HER2-negative early breast cancer. Ribociclib is the only category 1 CDK4/6 inhibitor for first-line treatment in combination with an AI. The guidelines also add adjuvant ribociclib for premenopausal patients with HR-positive, HER2-negative disease, and revise other treatment pathways. The FDA approval of adjuvant ribociclib may apply to a wider population than abemaciclib, with ribociclib given at 400 mg for 3 years, compared to abemaciclib's 2 years.

FDA approved inavolisib with palbociclib and fulvestrant for PIK3CA-mutated, HR-positive, HER2-negative breast cancer, based on INAVO120 study showing improved PFS and ORR. Common adverse reactions include decreased neutrophils and haemoglobin. The treatment is part of Project Orbis, involving international regulatory collaboration.

The INAVO120 trial shows that adding the PI3Kα inhibitor inavolisib to standard endocrine plus CDK4/6 inhibitor therapy for PIK3CA-mutant HR+, HER2- breast cancer increases efficacy, with progression-free survival as the primary endpoint.

Inavolisib, a PI3Kα isoform-selective kinase inhibitor and monovalent degrader of mutant p110α, selectively depletes mutant p110α in cancer cells with active RTK signaling. It received FDA approval in October 2024 for use with palbociclib and fulvestrant in treating endocrine-resistant, PIK3CA-mutated, HR+/HER2- breast cancer.

FDA approvals in October 2024 include nivolumab for resectable NSCLC, inavolisib triplet for PIK3CA-mutated HR+/HER2– advanced breast cancer, Optune Lua for metastatic NSCLC, zolbetuximab plus chemotherapy for CLDN18.2+ gastric or GEJ adenocarcinoma, and asciminib for newly diagnosed Ph+ chronic-phase CML. Other approvals include Cologuard Plus for average-risk CRC and Ion Torrent Oncomine Dx Target Test for vorasidenib.

PredicineCARE™ enabled accurate identification of PIK3CA-mutated metastatic breast cancer patients in China, contributing to FDA approval of Inavolisib in the U.S.

PredicineCARE™ enabled accurate identification of PIK3CA-mutated metastatic breast cancer patients in China, contributing to FDA approval of Inavolisib. The PredicineCARE™ liquid biopsy assay demonstrated a 98.7% success rate and 5-day turnaround time, supporting targeted therapy like Itovebi.

FY 2025 appropriations negotiations are on hold due to the general election; NIH funding remains a focus for the medical research community. The FDA's Oncologic Drugs Advisory Committee discussed PD-L1 expression as a biomarker for anti-PD-1 therapies, potentially leading to changes in drug labeling. An FDA-AACR workshop on DPD deficiency testing before chemotherapy with fluoropyrimidines is scheduled for January 16, 2025. Representatives Wasserman Schultz and DeGette urged the FDA to finalize e-cigarette PMTA reviews. The FDA approved five oncology drugs and new indications between September 21 and October 25, 2024.

Inavolisib plus fulvestrant and palbociclib significantly improved progression-free survival (PFS) in HR+, HER2-, PIK3CA-mutated breast cancer patients, reducing progression risk by 57% compared to palbociclib alone (PFS 15.0 vs 7.3 months, HR 0.43). FDA approved inavolisib regimen in October 2024, supported by INAVO120 data.