There are differences in terms of breast cancer at the molecular level despite the similarity of their location within the body. There are genetic mutations that affect the growth of cancerous cells, survival of such cells, and even their response to any medication. One of the genetic mutations seen in breast cancer cases is PIK3CA mutation. Such mutation results in the activation of the PI3K signaling pathway. Alpelisib is a target-based drug that affects this particular pathway.
What Is PIK3CA-Mutated Breast Cancer?
PIK3CA is associated with the synthesis of one part of the PI3K protein, whose function is essential in the signaling pathways that regulate cell growth, metabolism, proliferation, and survival. Mutations may lead to a persistent activation of this pathway, thus giving cancer cells signals for their continuous growth. Mutations in PIK3CA are common in hormone receptor-positive breast cancer. However, the mutation itself is not the only factor that influences treatmen some other aspects should also be considered as well, such as the status of hormone receptors, HER2, tumor stage, prior therapy, etc.
What Is Alpelisib?
It is a medication that can be taken orally and is classified as targeted therapy. It mainly targets the alpha subunit of class I PI3K which is called PI3Kα. Unlike conventional chemotherapy which has a general effect on all rapidly dividing cells, this targeted therapy acts to inhibit a certain signal transduction pathway responsible for tumor growth. However, the medicine is combined with Fulvestrant for treatment of HR-positive, HER2-negative, and PIK3CA-mutated advanced or metastatic breast cancer in adult patients who have progressed after an endocrine therapy.
Why Is PIK3CA Testing Important?
PIK3CA testing is used to determine whether a tumor has a mutation that can make PI3K inhibitors a valid choice for treatment. This is a critical element of personalized medicine for breast cancer patients because not all breast cancer patients have the same response to the same targeted drug. Tests may be done by means of biopsy of tumor tissues or, using some FDA-approved diagnostics, through the use of blood samples with circulating tumor DNA. The FDA also provides a companion diagnostic tool for detecting PIK3CA mutations for the administration of Alpelisib.
What Is the Mechanism of Action of Targeted Therapy in Breast Cancer?
The medicine acts through the inhibition of PI3Kα, an important element of the PI3K signaling pathway. Mutations in the gene of PIK3CA lead to increased activity of this pathway, thus allowing cancer cells to receive proliferative and survival signals. Inhibition of PI3Kα by the tablet prevents such signals from appearing. It is used together with other medications because they have different modes of action. Alpelisib influences the PI3K signaling pathway while Fulvestrant inhibits the activity of the estrogen receptor in hormone receptor positive cancer cells.
When Is the Medicine Used?
The tablet is prescribed for a certain category of patients who have advanced or metastatic breast cancer with the following features:
- HR-positive breast cancer
- HER2-negative breast cancer
- PIK3CA-mutated breast cancer
- Advanced or metastatic disease
What Are the Benefits of Targeted Therapy In Breast cancer treatment?
One of the biggest advantages of tablet is that it acts upon a unique biological pathway instead of targeting all rapidly growing cells uniformly. Thus, the medicine exemplifies the concept of precision oncology wherein the drug treatment is decided based on the biological traits of the tumor. For appropriate patients, it has the potential to:
- Target abnormal PI3Kα pathway activity.
- Serve as a potential therapeutic approach for patients with PIK3CA mutations.
- Be used with other medications for inhibiting complementary pathways.
- Enable a personalized treatment approach for breast cancer treatment.
- Delay disease progression in selected patients.
The magnitude of benefit can differ, and the treatment response needs to be evaluated with appropriate clinical follow-up.
What Side Effects Should Be Expected By The Medicine?
Side effects associated with the medicine may vary from mild to severe. The primary problem that needs to be considered is hyperglycemia, or high blood glucose. It can affect glucose metabolism, which makes glucose monitoring necessary during therapy. Some of the most common side effects are:
- Diarrhea
- Rash
- Nausea
- High blood glucose
- Loss of appetite
- Weight loss
- Fatigue
- Vomiting
- Stomatitis
Which Brands Contain Alpelisib?
Some of the brands of this medicine are:
Availability of the brands may vary from one country to another. Patients should not choose a particular dosage on their own but must follow the prescription given by their healthcare provider.
What Monitoring Is Needed During Treatment?
Monitoring is an essential component of the treatment process with alpelisib, especially with regard to the impact of the drug on glucose levels. Before administration, fasting glucose and HbA1c must be evaluated, and blood sugar levels should be checked periodically thereafter. However, according to the condition of the patient, further monitoring can include:
- Skin manifestations
- Diarrhea and other gastrointestinal disorders
- Laboratory values related to the functioning of the liver
- Tolerance of the treatment regimen
- Body mass and appetite
- Effectiveness of the treatment in general
In the event of severe adverse effects, the oncologist might need to suspend the treatment temporarily or even permanently.
What Is the Future of Targeted Therapy in Breast Cancer?
Targeted therapy is becoming more and more associated with breakthroughs in the field of molecular diagnostics. With each additional biomarker discovered, scientists can create treatment methods based on certain molecular processes. Testing for PIK3CA mutations is an illustration of such a process. In the future, there might be even more sensitive diagnostics, better drug combinations, and techniques to overcome drug resistance. All of these will only enhance the role of personalized treatment in breast cancer therapy.
Can Alpelisib Interact With Other Medicines?
The use of medicine can cause drug interaction with some therapies, which means that the use of the tablet needs to be properly considered if there is an intake of other medications. According to the FDA prescribing information, there should be avoidance of strong CYP3A4 inducer and avoidance of BCRP inhibitor whenever possible because of toxicity during the treatment.
Conclusion
The Alpelisib is an example of how information gained from genes can contribute to the treatment of breast cancer. This medication works by inhibiting PI3Kα, and it is used to treat abnormal signaling that is caused by mutations in PIK3CA. It is combined with other medicines to treat advanced or metastatic breast cancer that is estrogen receptor positive and HER2 negative, after failure to respond to endocrine therapy.
FAQs
1. Does the medicine lead to hyperglycemia?
Yes, the tablet may cause hyperglycemia in some patients which is why it imprortant to monitor, blood sugar levels need before and during the treatment.
2. PIK3CA testing need to be done before the administration of the targeted therapy?
Yes, the selection of this drug is based on testing for an appropriate mutation in the PIK3CA gene.
References
- André, F., Ciruelos, E., Rubovszky, G., Campone, M., Loibl, S., Rugo, H. S., … & Juric, D. (2019). Alpelisib for PIK3CA-mutated, hormone receptor–positive advanced breast cancer. New England Journal of Medicine, 380(20), 1929-1940. Https://www.nejm.org/doi/full/10.1056/NEJMoa1813904
- Tufail, M., Hu, J. J., Liang, J., He, C. Y., Wan, W. D., Huang, Y. Q., … & Li, N. (2024). Predictive, preventive, and personalized medicine in breast cancer: targeting the PI3K pathway. Journal of translational medicine, 22(1), 15. Https://www.researchgate.net/publication/377112270_Predictive_preventive_and_personalized_medicine_in_breast_cancer_targeting_the_PI3K_pathway
- Narayan, P., Prowell, T. M., Gao, J. J., Fernandes, L. L., Li, E., Jiang, X., … & Beaver, J. A. (2021). FDA approval summary: alpelisib plus fulvestrant for patients with HR-positive, HER2-negative, PIK3CA-mutated, advanced or metastatic breast cancer. Clinical Cancer Research, 27(7), 1842-1849. Https://pubmed.ncbi.nlm.nih.gov/33168657/
- Chang, D. Y., Ma, W. L., & Lu, Y. S. (2021). Role of alpelisib in the treatment of PIK3CA-mutated breast cancer: patient selection and clinical perspectives. Therapeutics and clinical risk management, 193-207. Https://www.researchgate.net/publication/350041551_Role_of_Alpelisib_in_the_Treatment_of_PIK3CA-Mutated_Breast_Cancer_Patient_Selection_and_Clinical_Perspectives
- Masoud, V., & Pagès, G. (2017). Targeted therapies in breast cancer: New challenges to fight against resistance. World journal of clinical oncology, 8(2), 120. https://pmc.ncbi.nlm.nih.gov/articles/PMC5385433/
