Inavolisib

FDA approves inavolisib triplet therapy for ER+/HER2- breast cancer with PIK3CA mutation, significantly extending progression-free survival in phase 3 trial.

The FDA approved inavolisib in combination with palbociclib and fulvestrant for endocrine-resistant, PIK3CA-mutated, HR-positive, HER2-negative, locally advanced or metastatic breast cancer. The FoundationOne Liquid CDx assay was also approved as a companion diagnostic. The approval was based on the INAVO120 trial, showing median PFS of 15 months vs. 7.3 months with ORR of 58% vs. 25%. Common adverse reactions included decreased neutrophils, decreased hemoglobin, and increased fasting glucose.

The FDA approved inavolisib (Itovebi) plus palbociclib and fulvestrant for endocrine-resistant, PIK3CA-mutant, HR-positive, HER2-negative advanced breast cancer. The approval is based on the INAVO120 trial, showing improved progression-free survival (PFS) and objective response rate (ORR) with inavolisib. Common adverse events included decreased neutrophils, hemoglobin, and platelets, and increased fasting glucose and creatinine.

FDA approves inavolisib (Itovebi) with palbociclib and fulvestrant for endocrine-resistant, PIK3CA-mutated, HR-positive, HER2-negative, locally advanced or metastatic breast cancer. INAVO120 trial showed median PFS of 15.0 months vs 7.3 months with placebo, and ORR of 58% vs 25%. Inavolisib recommended dose is 9 mg once daily.

Yuan Yuan discusses the rise of CDK4/6 inhibitors and ADCs in breast cancer treatment, highlighting uncertainties in eligibility, resistance, and sequencing. She mentions clinical trials like monarchE and NATALEE, and the importance of personalized radiation therapy and emerging ADCs. Yuan also addresses the need for research to understand drug resistance and the future of ADCs in breast cancer treatment.

Inavolisib (GDC-0077) showed a disease control rate (DCR) of 60% at 8 weeks and 32% at 16 weeks in patients with PIK3CA-mutated advanced solid tumors, with a favorable safety profile. The median progression-free survival was 3.52 months, and the 12-month overall survival rate was 51%. The most common adverse effects were hyperglycemia, diarrhea, fatigue, and constipation, mostly grade 1 or 2.

FDA reviews DFD-29 for rosacea, eladocagene exuparvovec for AADC deficiency, inavolisib for PIK3CA-mutated HR-positive breast cancer, acoramidis for transthyretin amyloid cardiomyopathy, and zanidatamab for HER2-amplified biliary tract cancer, with PDUFA dates in November 2024.

Novel anti-estrogen therapies, including PI3K pathway inhibitors like inavolisib, show promise in treating ER-positive advanced breast cancer, particularly in patients with PIK3CA mutations. These therapies, often used in combination with existing treatments like palbociclib and fulvestrant, aim to improve progression-free survival and overall outcomes. Personalized treatment strategies are evolving, focusing on identifying specific patient subgroups that may benefit most from these novel agents.