Introduction
The FDA has recently approved a new combination therapy, marking a significant advance in the treatment of endocrine-resistant, PIK3CA-mutated, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, advanced breast cancer. This combination involves inavolisib (Itovebi), palbociclib, and fulvestrant, offering new hope to patients with recurrent disease after adjuvant endocrine therapy.
Current Regulatory Status
Inavolisib, developed by Genentech, Inc., has been approved alongside palbociclib and fulvestrant for adults with locally advanced or metastatic breast cancer. The approval follows a rigorous clinical evaluation and was conducted under the FDA’s Project Orbis, in collaboration with regulatory agencies in Australia, Canada, and Switzerland. The FDA has also approved the FoundationOne Liquid CDx assay as a companion diagnostic tool to identify patients eligible for this treatment.
Drug Details
Inavolisib is an oral PIK3CA inhibitor, designed to target and inhibit the PIK3CA mutations that drive cancer growth. When combined with palbociclib, a CDK4/6 inhibitor, and fulvestrant, an estrogen receptor antagonist, the regimen provides a multi-targeted approach to slow disease progression in patients resistant to traditional endocrine therapies.
Trial Details
Efficacy and safety of the combination therapy were evaluated in the INAVO120 trial (NCT04191499), a double-blind, placebo-controlled, multicenter study involving 325 patients. All participants had progressed during or within 12 months of completing adjuvant endocrine therapy. Patients were randomized to receive inavolisib or placebo, combined with palbociclib and fulvestrant, until disease progression or unacceptable toxicity.
Key Outcomes
The primary efficacy measure was progression-free survival (PFS), with inavolisib showing a median PFS of 15.0 months compared to 7.3 months in the placebo group. The objective response rate (ORR) in the inavolisib arm was 58%, significantly higher than the 25% observed in the placebo group. Additionally, the median duration of response (DOR) was 18.4 months for inavolisib compared to 9.6 months for the placebo group. Though overall survival analysis is still ongoing, interim results indicate a promising trend toward improved outcomes.
Conclusion
The FDA’s approval of inavolisib in combination with palbociclib and fulvestrant introduces a crucial new option for patients with advanced breast cancer, particularly those with PIK3CA mutations. Supported by strong efficacy data and careful international collaboration, this combination therapy promises to fill a significant gap in the treatment landscape for patients resistant to endocrine therapies.
Dr. Vinoth Khandelwal, Ph.D.
Disclaimer
The editors take care to share authentic information. In case of any discrepancies please write to newsletter@medness.org
The sponsors do not have any influence on the nature or kind of the news/analysis reported in MedNess. The views and opinions expressed in this article are those of the authors and do not necessarily reflect the official policy or position of MedNess. Examples of analysis performed within this article are only examples. They should not be utilized in real-world analytic products as they are based only on very limited and dated open-source information. Assumptions made within the analysis are not reflective of the position of anyone volunteering or working for MedNess. This blog is strictly for news and information. It does not provide medical advice, diagnosis or treatment nor investment suggestions. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
MedNess is a part of STEMPeers® which is a 501(c)(3) organization registered in PA as PhD Career Support Group. The organization helps create a growing network of STEM scientists that is involved in peer-to-peer mentoring and support.
