On October 10, 2024, the Food and Drug Administration (FDA) approved Inavolisib, in combination with Palbociclib and Fulvestrant, for adults with advanced breast cancer that meets specific criteria. This approval is essential for patients who have:
- Endocrine-resistant breast cancer
- PIK3CA-mutated tumors
- Hormone receptor (HR)-positive status
- HER2-negative status
- Locally advanced or metastatic disease, as identified by an FDA-approved test
- Experienced recurrence after finishing the previous endocrine therapy
Study Overview
The INAVO120 study is a Phase III clinical trial that tested the effectiveness and safety of inavolisib in combination with Palbociclib and fulvestrant, compared with placebo plus Palbociclib and fulvestrant. It focused on PIK3CA-mutated, hormone receptor (HR)-positive, HER2-negative breast cancer that had advanced locally or metastasized and was resistant to endocrine therapy. These are some key points from the study.
The study involved 325 patients with advanced breast cancer whose condition worsened after completing endocrine therapy.
Patients were divided into two groups:
- One group received Inavolisib (9 mg once daily), Palbociclib (125 mg once daily for 21 days, followed by seven days off), and Fulvestrant (500 mg administered on specific days).
- The other group received a placebo instead of Inavolisib.
The primary endpoint was progression-free survival (PFS), defined as the time to progression or death.
Results of the Study
- The median PFS was 15.0 months in the treatment group (Inavolisib + Palbociclib + Fulvestrant) compared with 7.3 months in the placebo group.
- The overall response rate (ORR) was 58% in the treatment group, compared with only 25% in the placebo group.
- The duration of response (DOR) was 18.4 months in the treatment group, compared with 9.6 months in the placebo group.
Common Side Effects
Patients taking this combination of treatments experienced some side effects. The most common effects include:
- Decreased neutrophils (a type of white blood cell)
- Decreased hemoglobin (which can lead to anemia)
- Increased fasting glucose
- Stomatitis (inflammation of the mouth)
- Diarrhea
- Fatigue
Companion Diagnostic Device Approved
The FoundationOne Liquid CDx assay was approved as a companion diagnostic tool. This test helps identify breast cancer patients who may benefit from Inavolisib, Palbociclib, and Fulvestrant.
Fast-Tracked Approval
This approval was part of Project Orbis, which allows multiple countries to review cancer drugs simultaneously. The FDA collaborated with health authorities from Australia, Canada, and Switzerland. This application received priority review and breakthrough designation, allowing approval seven weeks earlier than expected.
About Hormone Receptor-Positive Breast Cancer
What is HR-Positive Breast Cancer?
- This type of breast cancer makes up about 70% of all breast cancer cases.
- Tumor cells have receptors for hormones like estrogen and progesterone, which fuel their growth.
- Many patients with this type of cancer face challenges with disease progression and resistance to treatments.
Role of PI3K Pathway
The PI3K pathway is often too active in HR-positive breast cancer because of PIK3CA mutations. This makes the cancer resistant to standard hormone treatments.
How Does Inavolisib Work?
Inavolisib is an oral drug that targets PIK3CA mutations, which are found in about 40% of HR-positive breast cancers. These mutations can accelerate tumor growth and confer resistance to standard treatments. It specifically inhibits PI3Kα, slowing cancer growth driven by these mutations.
Roche’s Commitment to Breast Cancer Research
About Roche
- Roche has been at the forefront of breast cancer research for over 30 years, working to develop better treatments for patients across different types of breast cancer.
- The company focuses on personalized healthcare and works to bring innovative treatments, such as Inavolisib, to those in need.
Next Steps
- Roche plans to submit the data from this study to health authorities so that this treatment can be made available to patients as soon as possible.
- PIK3CA mutations lead to resistance to traditional hormone therapies.
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