PIK3 Inhibitor Inavolisib Could Delay The Need For Chemo
- About 35 to 40% of people with a type of advanced breast cancer known as hormone-receptor positive (HR+), HER2 negative (HER2-) have something called a PIK3CA mutation.
- These mutations are often stubborn and find ways to outsmart standard therapies like hormone treatment and CDK4/6 inhibitors — but now, a new treatment combination is providing hope.
- A large study showed that adding a PIK3 inhibitor called inavolisib to the standard of care, a combination of palbociclib and fulvestrant, extended survival and more than doubled the time before cancer grew again.
- Adding the drug extended overall survival to 34 months vs. 27 months with the standard and delayed the need for chemotherapy by an average of two years.
Inavolisib (brand name Itovebi) is designed to address that issue. Earlier drugs in its class have worked, but caused widespread side effects. Inavolisib offers a more targeted approach.
Read More- People lived about seven months longer on average (34 months vs. 27 months)
- The cancer stayed quiet more than twice as long (17.2 months vs. 7.3 months)
- The need for chemotherapy was pushed back from roughly one year to almost three years
Because of these benefits, the FDA approved inavolisib in October 2024 for women and men whose metastatic, estrogen-driven breast cancers carry the PIK3CA mutation.
This study involved 325 participants with hormone receptor-positive (HR+), HER2-negative locally advanced or metastatic breast cancer.
What Is HR+ Breast Cancer?
Hormone receptors are proteins found on breast cells that pick up either estrogen or progesterone signals and promote cell growth. If the cancer has one of those receptors, meaning it is hormone receptor-positive (HR+), the hormones help the cancer to grow.
Breast tumors may be positive for estrogen receptors (ER+), progesterone receptors (PR+) or both (ER/PR+). About 80% of all HR+ breast cancers are ER+ or ER/PR+, according to Penn Medicine.
What Is HER2- Breast Cancer?
HER2 stands for human epidermal growth factor receptor 2. It’s a protein that can be found on the surface of breast cancer cells and make them grow quickly.
Tumors can be HER-negative, meaning they show minimal or no expression of the protein.
Tumors can also be HER2-low or HER2-positive, depending on the level of the protein present. These respond well to treatments that target the HER2 protein, such as Enhertu (trastuzumab deruxtecan) or Herceptin (trastuzumab).
Could Inavolisib Be Part Of Your Treatment?
To be eligible for the treatment approach that uses inavolisib, you must have:
- Metastatic or inoperable HR+, HER2- breast cancer
- A documented PIK3CA mutation (by blood test or tissue biopsy)
- No prior treatment for metastatic disease or progression after endocrine therapy alone
If that sounds like your situation, ask your oncologist whether the triple regimen fits your overall plan. For some, inavolisib treatment starts right away; for others, it joins the team when earlier therapies lose steam. Either way, getting genomic testing early ensures the option is on the table.
Inavolisib Treatment: What To Expect
If inavolisib is added to your treatment plan, you can expect a treatment schedule like the following:
- Fulvestrant injections: Given on day 1 and 15 of the first month, then once a month
- Palbociclib capsules: Taken daily for 21 days, then one week off (repeated every 28 days)
- Inavolisib tablet: One pill taken every day, without breaks
The drugs work together because fulvestrant blocks estrogen signaling, palbociclib slows cell-cycle churn, and inavolisib disables the PI3K escape hatch.
Side Effects: What To Expect
The triple combo is not without bumps. Most side effects are manageable when you address them early, much like patching a small roof leak before storm season.
The most common issues include:
- High blood sugar
- Diarrhea
- Mouth sores
- Eye irritation
- Low white-blood-cell counts
To track and mitigate these side effects early on, patients can do things like checking fasting glucose regularly, having anti-diarrhea medication available at home, rinsing with special solutions after meals, using eye drops, and more.
Looking To The Future
While the results of the INAVO120 trial are promising, it’s important to understand a few limitations.
For example, many patients in the study received palbociclib, which is used less frequently now. Some doctors prefer ribociclib or abemaciclib instead.
Also, most participants hadn’t received CDK4/6 inhibitors earlier in their treatment, which is more common today.
Finally, because high blood sugar was a common side effect, patients with diabetes were not included in the trial. It’s not yet clear if this drug is for them.
Even with these caveats, the data is strong, but ongoing studies will help clarify how best to use this new drug in real-world settings.
The Importance Of Biomarker Testing
This study underscores the importance of biomarker testing for patients with advanced or metastatic breast cancer. A single test can expand your treatment options, making it crucial to ask your doctor about testing for biomarkers like the PIK3CA mutation.
“This treatment is an excellent example of what’s called precision oncology. We need to match the right patient to the right treatment at the right time. To do that, we have to follow a specific criteria,” Dr. Dejan Juric, Medical Oncologist at Mass General Cancer Center, told SurvivorNet in a previous conversation.
“Patients have to ask their physicians, do I qualify for this type of treatment? Have you analyzed my disease? Are you just relying on old school methods of analysis, estrogen receptor, progesterone receptor, HER2? Have you checked for mutations in this cancer? Drivers of this disease?”
Ask your doctor if the cancer was already tested for biomarkers, including PIK3CA mutations. If not, ask about testing options.
Approximately 40% of hormone receptor-positive metastatic breast cancers have this mutation and Inavolisib works by blocking the activity of the PI3K protein. If the tumor tests positive, Inavolisib could be a potential treatment.
Questions To Ask Your Doctor
- Have we already tested my tumor or blood for a PIK3CA mutation?
- If I start inavolisib now, what labs and scans will monitor safety and success?
- How would you handle high blood sugar if it shows up?
- Could a dose break or reduction keep me on therapy longer if diarrhea becomes an issue?
- What’s our game plan if the cancer grows again—clinical trials, new combinations, or something else?
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