Metastatic Breast Cancer Drugs That Target PI3 Kinase, PTEN, AKT and mTOR
The PI3 kinase, AKT, PTEN and mTOR cellular pathway
The PI3 kinase, AKT, PTEN and mTOR enzymes are all on the same cellular pathway. They are important in cell growth and cell division.
PI3 kinase inhibitors, AKT inhibitors and mTOR inhibitors are drugs that target different parts of this pathway to block cancer growth.
Drugs that target the PI3 kinase, AKT, PTEN and mTOR cellular pathway
Drug category |
Drug name |
Brand name |
How is it given? |
PI3 kinase inhibitors |
Piqray |
Pill |
|
Itovebi |
Pill |
||
AKT inhibitor |
Truqap |
Pill |
|
mTOR inhibitor |
Afinitor |
Pill |
PI3 kinase inhibitors
What are PI3 kinase inhibitors?
The PI3 kinase, AKT, PTEN and mTOR enzymes are all on the same cellular pathway. They are important in cell growth and cell division.
Some breast cancers have a PIK3CA gene mutation. These are mutations in the genes of the breast cancer cells, not the genes of the person.
A PIK3CA tumor gene mutation can affect PI3 kinase activity and cause the cancer to grow. PI3 kinase inhibitors are designed to block this action. Metastatic breast cancers that have a PIK3CA tumor gene mutation can be treated with a PI3 kinase inhibitor.
The PI3 kinase inhibitors used for metastatic breast cancer treatment are:
- Alpelisib (Piqray)
- Inavolisib (Itovebi)
Testing for PIK3CA tumor gene mutations
All hormone receptor-positive, HER2-negative metastatic breast cancers are tested for PIK3CA tumor gene mutations [4,6].
Testing for tumor gene mutations can be done by testing the tumor DNA in your blood or by testing tumor tissue (from a biopsy) [6].
Alpelisib (Piqray) and metastatic breast cancer treatment
Alpelisib in combination with the hormone therapy drug fulvestrant is FDA-approved to treat hormone receptor-positive, HER2-negative metastatic breast cancers that:
- Have a PIK3CA tumor gene mutation
- Have been treated with at least one hormone therapy in the past
The combination of alpelisib and fulvestrant can give people more time before the cancer worsens compared to fulvestrant alone [25].
| For a summary of research studies on PI3 kinase inhibitors and metastatic breast cancer treatment, visit the Breast Cancer Research Studies section. |
Learn about emerging areas in treatment for metastatic breast cancer.
Inavolisib (Itovebi) and metastatic breast cancer treatment
Inavolisib in combination with the CDK4/6 inhibitor palbociclib and the hormone therapy drug fulvestrant is FDA-approved to treat hormone receptor-positive, HER2-negative metastatic breast cancers that:
- Have a PIK3CA tumor gene mutation
- Have progressed on past hormone therapy
The combination of inavolisib, palbociclib and fulvestrant can give people more time before the cancer worsens and can improve survival compared to palbociclib and fulvestrant alone [26-28].
Of note, the clinical trial that led to the FDA approval of inavolisib only included people who had breast cancers with high-risk features and who got the combination of inavolisib, palbociclib and fulvestrant as their first treatment for metastatic breast cancer [27].
| For a summary of research studies on PI3 kinase inhibitors and metastatic breast cancer treatment, visit the Breast Cancer Research Studies section. |
Learn more about treatment for metastatic breast cancer.
Learn about emerging areas in treatment for metastatic breast cancer.
How are alpelisib and inavolisib given?
Alpelisib and inavolisib are pills.
Talk with your health care provider if you have any questions or concerns about taking your medications.
Side effects of alpelisib and inavolisib
Before you begin taking alpelisib or inavolisib, talk with your health care provider about possible side effects and how to manage them.
|
Side Effects |
Alpelisib |
Possible side effects include diarrhea, nausea, decreased appetite, rash, vomiting, mouth sores, fatigue and hair loss. Alpelisib can cause high blood sugar levels. Your blood sugar levels will be checked before and during treatment because nearly everyone who takes alpelisib gets high blood sugar levels. It’s recommended you take an antihistamine, such as cetirizine (Zyrtec), to lower the risk of rash. |
Inavolisib |
Possible side effects include mouth sores, diarrhea, decreased white blood cell counts, nausea, decreased appetite, rash, vomiting, fatigue and hair loss. Inavolisib can cause high blood sugar levels. Your blood sugar levels will be checked before and during treatment because over half of the people who take inavolisib get high blood sugar levels. |
Adapted from select sources [27,29]. |
|
Learn more about side effects.
AKT inhibitors
What are AKT inhibitors?
The PI3 kinase, AKT, PTEN and mTOR enzymes are all on the same cellular pathway. They are important in cell growth and cell division.
Some breast cancers have a PIK3CA, AKT1 or PTEN gene mutation. These are mutations in the genes of the breast cancer cells, not the genes of the person.
A PIK3CA, AKT1 or PTEN tumor gene mutation can affect AKT activity and cause the cancer to grow. AKT inhibitors are designed to block this action.
The AKT inhibitor capivasertib (Truqap) can be used to treat some metastatic breast cancers that have a PIK3CA, AKT1 or PTEN tumor gene mutation.
Testing for PIK3CA, AKT1 or PTEN tumor gene mutations
All hormone receptor-positive, HER2-negative metastatic breast cancers are tested for PIK3CA, AKT1 and PTEN tumor gene mutations [4,6]. These mutations are in the genes of the tumor cells, not in the genes of the person.
Testing for tumor gene mutations can be done by testing the tumor DNA in your blood or by testing tumor tissue [6].
Capivasertib (Truqap) and metastatic breast cancer treatment
Capivasertib in combination with the hormone therapy drug fulvestrant is FDA-approved to treat some hormone receptor-positive, HER2-negative metastatic breast cancers that:
- Have a PIK3CA, AKT1 or PTEN tumor gene mutation
- Have been treated with at least one hormone therapy in the metastatic setting in the past
The combination of capivasertib and fulvestrant can give people more time before the cancer worsens compared to fulvestrant alone [30].
| For a summary of research studies on AKT inhibitors and metastatic breast cancer treatment, visit the Breast Cancer Research Studies section. |
Learn more about treatment for metastatic breast cancer.
Learn about emerging areas in treatment for metastatic breast cancer.
How is capivasertib given?
Capivasertib is a pill.
Talk with your health care provider if you have any questions or concerns about taking your medications.
Side effects of capivasertib
Before you begin taking capivasertib, talk with your health care provider about possible side effects and how to manage them.
|
Side Effects |
Capivasertib |
Possible side effects include diarrhea, rash and other skin problems, decreased white blood cell counts, nausea, vomiting, mouth sores and fatigue. Capivasertib can cause high blood sugar levels. Your blood sugar levels will be checked before and during treatment with capivasertib. |
Adapted from select sources [31]. |
|
Learn more about side effects.
mTOR Inhibitors
What are mTOR inhibitors?
The PI3 kinase, AKT, PTEN and mTOR enzymes are all on the same cellular pathway. They are important in cell growth and cell division.
mTOR (mammalian target of rapamycin) inhibitors are drugs that may slow the growth of cancer cells and increase the benefit of hormone therapy.
The mTOR inhibitor everolimus (Afinitor) can be used to treat some hormone receptor-positive metastatic breast cancers.
Everolimus (Afinitor) and metastatic breast cancer treatment
Everolimus is FDA-approved for the treatment of hormone receptor-positive, HER2-negative metastatic breast cancers in postmenopausal women.
The combination of everolimus and hormone therapy can slow the growth of these cancers better than hormone therapy alone [32-33].
Learn more about treatment for metastatic breast cancer.
Learn about emerging areas in treatment for metastatic breast cancer.
How is everolimus given?
Everolimus is a pill.
Talk with your health care provider if you have any questions or concerns about taking your medications.
Side effects of everolimus
Before you begin taking everolimus, talk with your health care provider about possible side effects and how to manage them.
|
Side Effects |
Everolimus |
Possible side effects include mouth sores, infections, rash, fatigue, diarrhea, high blood sugar and decreased appetite. In rare cases, everolimus can cause lung inflammation, which can lead to death. Tell your health care provider right away if you have shortness of breath or other breathing problems while taking this drug. Mouth sores with everolimus can be prevented with a dexamethasone (steroid) mouthwash. |
Adapted from select sources [34]. |
|
Learn more about side effects.
Ashley Fernandez, living with metastatic breast cancer
“What keeps me going is my new normal. My life with cancer is completely different, I know I have it and I live with it every single day but it doesn’t take over every single day.”
Treatment guidelines for metastatic breast cancer
Although the exact treatment for metastatic breast cancer varies from person to person, guidelines help make sure high-quality care is given. These guidelines are based on the latest research and agreement among experts.
The National Comprehensive Cancer Network (NCCN) and the American Society of Clinical Oncology (ASCO) are respected organizations that regularly review and update their guidelines.
In addition, the National Cancer Institute (NCI) has treatment overviews.
Talk with your health care team about which treatment guidelines they follow.
Monitoring metastatic breast cancer
You’ll be monitored (checked) regularly with scans to see if the cancer is responding to treatment. If the treatment is no longer working, or you’re having a lot of side effects, your health care provider will change your treatment or discuss other options.
Learn more about how metastatic breast cancer is monitored.
Clinical trials
Clinical trials offer the chance to try new treatments and possibly benefit from them. They can also study other parts of care, such as ways to manage side effects. We encourage you to talk with your oncologist and consider joining a clinical trial if there’s one right for you.
Some clinical trials are available as the first step in treating metastatic breast cancer. Others are for later in the disease course.
Consider joining a clinical trial when you’re newly diagnosed, when your oncologist is considering changing treatments or when there are limited treatment options.
Read our blogs:
- Four Things to Know About Clinical Trials When You’re Diagnosed with Breast Cancer
- How Do You Thank Someone for Time
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Susan G. Komen® Patient Care Center |
If you or a loved one needs information or resources about clinical trials, the Patient Care Center can help. Contact the Komen Breast Care Helpline at 1-877-465-6636 or email clinicaltrialinfo@komen.org. Se habla español. |
Metastatic Trial Search |
The Metastatic Trial Search is an online clinical trial matching tool that can help you find clinical trials that fit your needs. You can also register to receive Trial Alerts. |
Learn more about clinical trials for people with metastatic breast cancer.
Learn what Komen is doing to help people find and participate in breast cancer clinical trials, including trials supported by Komen.
Learn how Komen-funded research is improving treatment for breast cancer.
Prescription drug assistance
The cost of drug therapies for metastatic breast cancer can quickly become a financial burden for you and your family.
Medicare and many insurance companies offer prescription drug plans. One may already be included in your policy, or you may be able to buy an extra plan for prescriptions.
Many hospitals have financial counselors who can discuss insurance and cost coverage with you.
You may qualify for programs that help with drug costs or offer low-cost or free prescriptions. A financial counselor or social worker at your hospital can help you learn about these programs.
Learn more about insurance plans and prescription drug assistance programs.
Learn more about other financial assistance programs.
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Komen Financial Assistance Program |
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Susan G. Komen® created the Komen Financial Assistance Program to help those struggling with the costs of breast cancer treatment by providing financial assistance to eligible individuals. To learn more about this program and other helpful resources, call the Komen Patient Care Center at 1-877 GO KOMEN (1-877-465-6636) or email helpline@komen.org. Se habla español. Learn about other financial assistance programs. |
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Susan G. Komen®‘s position on fairness in oral cancer drug coverage |
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Insurance coverage of oral cancer drugs Cancer medications given through an IV into a vein or by an injection (under the skin or into a muscle) are usually covered under a health insurance plan’s medical benefit. However, oral cancer drugs (cancer medications that are pills) are usually covered under a health insurance plan’s prescription drug benefit. As a result, people often find themselves facing high out-of-pocket costs when filling prescriptions for oral cancer drugs. Sometimes these costs can be thousands of dollars a month. The impact of high cost-sharing High prescription drug costs and the resulting out-of-pocket burden on patients are a barrier to health care. They can prevent people from getting the medications prescribed by their health care providers. No one should be forced to get less appropriate treatment because an insurer gives more coverage for IV and injectable drugs than for pills. Efforts to increase fairness in drug coverage Komen supports state and federal efforts to require insurers to provide the same or better coverage for oral cancer drugs as they do for IV and injectable cancer drugs. This would help make sure patients have access to affordable, appropriate treatment. Become a Komen Advocacy Insider Sign up to be a Komen Advocacy Insider and get informed when action is needed on oral drug coverage parity at the state or national level. |
SUSAN G. KOMEN® METASTATIC BREAST CANCER SUPPORT RESOURCES |
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Updated 03/13/26
This content is regularly reviewed by an expert panel including researchers, practicing clinicians and patient advocates.
