Alpelisib: how it targets PIK3CA-mutant breast cancer

Alpelisib is a targeted cancer drug that zeros in on tumors with a PIK3CA mutation. That mutation is common in hormone receptor–positive, HER2-negative advanced breast cancer. If your tumor carries PIK3CA, alpelisib plus hormonal therapy can slow cancer growth where standard hormone therapy alone may no longer work.

How alpelisib works

Alpelisib blocks the PI3K alpha enzyme, a signaling switch inside cancer cells that helps them grow and resist hormone therapy. By shutting that switch off, alpelisib makes hormone drugs—most often fulvestrant—work better. Important: treatment only makes sense when a validated test shows a PIK3CA mutation. Your oncologist will order a tissue or liquid biopsy to confirm that.

The usual approved dose is 300 mg once daily with food, given with fulvestrant in the approved setting. Doctors may pause or reduce dose if side effects become a problem. Alpelisib is prescription-only and given as oral tablets, so you'll take it at home but with close clinic follow-up.

Side effects and monitoring

Some side effects are common and can be serious if not watched. The most frequent are high blood sugar (hyperglycemia), rash, diarrhea, nausea, and mouth sores (stomatitis). Less common but serious issues include inflammation of the lungs (pneumonitis) and liver test changes.

Before starting, expect baseline labs: fasting glucose or A1c, liver tests, and electrolytes. During treatment, your team will check fasting glucose regularly—often weekly at first—because hyperglycemia can appear quickly. If blood sugar rises, doctors may start metformin or adjust alpelisib dosing and involve an endocrinologist.

For skin rash and mouth sores, simple measures help: protect your skin from sun, use gentle oral rinses, report new blisters or severe mouth pain early. For diarrhea, stay hydrated and use anti-diarrheal meds if advised. Any new shortness of breath, cough, or unexplained fever needs prompt review.

Drug interactions matter. Alpelisib is affected by strong CYP3A modifiers, so tell your doctor about all medicines and supplements (including St. John's wort). Avoid starting new prescriptions without checking.

Who should avoid alpelisib? Pregnant people must not take it because of harm to a fetus. If you have uncontrolled diabetes, ask your team how to stabilize sugars first—high blood sugar is a known risk with this drug.

Bottom line: alpelisib gives a clear benefit when a PIK3CA mutation is present, but it demands active monitoring and prompt symptom reporting. Talk openly with your oncologist about mutation testing, blood sugar plans, and what to do at the first sign of side effects—early action keeps treatment on track.