On October 10, 2024, the FDA approved a new and promising treatment for patients with advanced breast cancer: inavolisib (Itovebi), in combination with palbociclib and fulvestrant. This new approval offers fresh hope for patients with endocrine-resistant, PIK3CA-mutated, hormone receptor (HR)-positive, and HER2-negative breast cancer, especially those whose disease has progressed after endocrine therapy. The approval also includes the FoundationOne Liquid CDx assay, a diagnostic test used to identify patients who are likely to benefit from this treatment.
This breakthrough marks a significant advance in the treatment of breast cancer, particularly for those who have limited options after their cancer has become resistant to standard endocrine therapies.
Understanding Inavolisib and Its Combination Therapy
Inavolisib is a selective PI3K inhibitor, targeting a mutation in the PIK3CA gene, which is commonly found in HR-positive breast cancer and associated with cancer growth. By combining inavolisib with palbociclib (a CDK4/6 inhibitor) and fulvestrant (a selective estrogen receptor degrader), this regimen targets multiple pathways that breast cancer cells use to grow, aiming to improve outcomes for patients who have seen their disease progress despite previous treatments.
This approval was based on the results from the INAVO120 trial (NCT04191499), a randomized, double-blind, placebo-controlled study that enrolled 325 patients with locally advanced or metastatic PIK3CA-mutated breast cancer. These patients had already experienced progression during or shortly after completing adjuvant endocrine therapy and had not received prior systemic therapy for their advanced disease.
Promising Results: Efficacy of Inavolisib
The INAVO120 trial showed encouraging outcomes for patients treated with inavolisib, palbociclib, and fulvestrant:
- Progression-Free Survival (PFS): Patients in the inavolisib arm had a median PFS of 15.0 months, compared to 7.3 months in the placebo group. This nearly doubled the time patients remained progression-free, offering significantly more time before the disease worsened.
- Objective Response Rate (ORR): The response rate was also significantly higher, with 58% of patients in the inavolisib group experiencing a measurable response to treatment, compared to only 25% in the placebo group.
- Duration of Response (DOR): The median duration of response in the inavolisib group was 18.4 months, compared to 9.6 months in the placebo group, demonstrating the lasting impact of the treatment on cancer control.
Although the interim analysis of overall survival (OS) did not reach statistical significance, it did support a positive trend, with a hazard ratio of 0.64. This means patients receiving inavolisib had a 36% reduction in the risk of death compared to those receiving the placebo.
Side Effects: What to Expect
As with any cancer therapy, it’s important to understand the potential side effects. In the trial, the most common adverse reactions (occurring in more than 20% of patients) included:
- Decreased neutrophils (white blood cells)
- Increased blood glucose levels
- Fatigue
- Stomatitis (mouth sores)
- Diarrhea
- Rash
- Headache
- Decreased appetite
While these side effects are manageable, patients should be closely monitored during treatment, and adjustments may be necessary if severe side effects occur.
Who is Eligible for This New Treatment?
This new treatment is specifically for patients with PIK3CA-mutated, HR-positive, HER2-negative breast cancer who have developed endocrine resistance—meaning their cancer has progressed despite the use of hormone therapies like tamoxifen or aromatase inhibitors.
If your oncologist suspects that you may be a candidate for this treatment, the FoundationOne Liquid CDx assay can be used to determine whether your cancer harbors the PIK3CA mutation, making you eligible for this new therapy.
Why This Approval is Important
The approval of inavolisib offers a new lifeline for patients with endocrine-resistant breast cancer who previously had limited options. By targeting a specific genetic mutation (PIK3CA) that drives cancer growth, this treatment allows for a more personalized approach, improving the chances of controlling the disease and prolonging survival.
With more than half of the patients in the trial experiencing a significant tumor response, this combination of inavolisib, palbociclib, and fulvestrant represents a powerful new option for women and men battling this aggressive form of breast cancer.
What’s Next?
Patients with advanced breast cancer should talk to their healthcare providers about whether inavolisib might be an option for them. As treatments continue to evolve, being aware of new therapies, clinical trials, and diagnostic tools can make a significant difference in managing the disease and improving quality of life.
About the Author
Dr. Thomas is a distinguished medical professional and a compassionate guide in the field of oncology. With over a decade of dedicated experience as a board-certified medical oncologist/internal medicine specialist, Dr. Thomas has become a trusted expert in the treatment of melanoma, sarcoma, and gastrointestinal conditions. With his many years of experience, he brings a wealth of expertise to the complex and challenging world of oncology. About Dr Thomas – MedOncMD