Alpelisib Treatment Eligibility Checker
This tool helps determine if a patient meets the key criteria for Alpelisib treatment as described in the article.
Enter your patient's information above to check eligibility.
When treating hormone receptor‑positive breast cancer, doctors have a new weapon: Alpelisib. This oral drug targets a key growth signal in many tumors and has reshaped how oncologists approach advanced disease.
Quick Takeaways
- Alpelisib is a selective PI3K inhibitor approved for HR+ breast cancer with a PIK3CA mutation.
- It works best when combined with endocrine therapy such as fulvestrant.
- Major side effects include hyperglycemia, rash, and diarrhea; proactive management is essential.
- Guidelines from the NCCN now list alpelisib as a preferred option after CDK4/6 inhibitor failure.
- Cost and insurance coverage remain challenges, but patient‑assistance programs exist.
How Alpelisib Works
The drug blocks the PI3K pathway, a molecular cascade that tells cancer cells to grow and resist death. In about 40% of HR+ tumors, the gene PIK3CA is mutated, causing the pathway to stay permanently switched on. By inhibiting the alpha isoform of PI3K, alpelisib shuts down that signal, slowing tumor proliferation and making cells more vulnerable to hormone‑blocking drugs.
Who Can Benefit?
Alpelisib is not a blanket cure for every breast cancer case. It is specifically approved for patients whose tumors test positive for a PIK3CA mutation and who have already progressed on a CDK4/6 inhibitor. Genetic testing is therefore the first step-most major oncology labs now offer a simple PCR‑based assay that returns results in a week.
Clinical Evidence Behind the Approval
The pivotal SOLAR‑1 trial (2020) enrolled over 1,300 patients with HR+ disease. In the PIK3CA‑mutated cohort, the combination of alpelisib plus fulvestrant extended median progression‑free survival (PFS) to 11.0 months versus 5.7 months with fulvestrant alone. A follow‑up real‑world study, the BYLieve trial, confirmed similar benefits in patients who had already received a CDK4/6 inhibitor.
How It’s Used With Other Therapies
Current practice pairs alpelisib with endocrine therapy-most commonly fulvestrant-because the two drugs attack the tumor from complementary angles. Some clinicians start with an aromatase inhibitor, then switch to the alpelisib/fulvestrant combo after CDK4/6 inhibitor failure. Ongoing trials are exploring triplet regimens that add a checkpoint inhibitor, but those are still investigational.
Safety Profile and Managing Side Effects
Side effects are a major reason why patients stop treatment early. The hallmark is hyperglycemia. Even patients without diabetes can develop blood‑sugar spikes; proactive monitoring and early use of metformin greatly reduce severe events. Other common issues include rash (often manageable with antihistamines) and diarrhea (treated with loperamide). The FDA label advises dose interruptions for Grade3 or higher toxicities, then re‑starting at a lower dose once symptoms improve.
Practical Considerations for Patients and Providers
- Dosage: The standard starting dose is 300mg once daily on an empty stomach. Dose reductions are made in 100mg steps based on tolerance.
- Monitoring: Baseline fasting glucose and HbA1c are required, followed by weekly checks for the first two months, then monthly thereafter.
- Insurance & Cost: Alpelisib is priced around $12,000 per month in the U.S. Many insurers cover it under oncology benefits, and the manufacturer runs a co‑pay assistance program for eligible patients.
- Guideline Placement: The NCCN 2024 breast cancer guidelines list alpelisib as a Category1 recommendation for PIK3CA‑mutated, post‑CDK4/6 inhibitor disease.
Comparison With Other PI3K Inhibitors
| Drug | Target Isoform | FDA Approval (2025) | Typical Side‑Effects |
|---|---|---|---|
| Alpelisib | PI3K‑α (selective) | HR+breast cancer, PIK3CA‑mutated | Hyperglycemia, rash, diarrhea |
| Buparlisib | Pan‑PI3K | None (trial discontinued) | Depression, liver toxicity |
| Pictilisib | Pan‑PI3K | None (investigational) | Gastro‑intestinal, skin rashes |
| Copanlisib | PI3K‑α/δ | Relapsed follicular lymphoma | Hyperglycemia, hypertension |
Frequently Asked Questions
Who should be tested for the PIK3CA mutation?
All patients with metastatic hormone‑receptor‑positive breast cancer should have tumor tissue or circulating‑DNA tested for PIK3CA mutations at diagnosis. The result determines eligibility for alpelisib.
Can alpelisib be used before a CDK4/6 inhibitor?
Current guidelines recommend CDK4/6 inhibitors as the first line after endocrine therapy. Alpelisib is reserved for later lines when the disease progresses despite a CDK4/6 inhibitor.
What should I do if I develop high blood sugar while on alpelisib?
Notify your oncologist immediately. Most clinicians start metformin and may temporarily pause alpelisib until glucose levels stabilize. Severe hyperglycemia (≥250mg/dL) requires dose reduction or discontinuation.
Is alpelisib covered by Medicare?
Yes, Medicare PartB typically covers oncology drugs administered in a clinic, while PartD may cover oral therapies like alpelisib. Patients should check with their plan and may qualify for manufacturer co‑pay assistance.
How long can a patient stay on alpelisib?
Treatment continues until disease progression or intolerable toxicity. Some patients have remained on therapy for more than two years with manageable side effects.
