Alpelisib

證據等級: L5

預測適應症: 1 個

Alpelisib: From Breast Cancer to Pulmonary Hypertension

One-Sentence Summary

Alpelisib is a PI3Kα inhibitor whose real-world use context in the evidence pack points to HR+/HER2-negative advanced or metastatic breast cancer (formal original-indication and MOA fields are not populated in this dataset). The TxGNN model predicts it may be effective for Pulmonary Hypertension, with a prediction score of 99.03%, but currently 0 directly relevant clinical trials and 2 publications support this direction — and both publications describe drug-induced pulmonary/cardiac toxicity rather than therapeutic benefit.

Quick Overview

Item	Content
Original Indication	Breast cancer (HR+/HER2-negative, advanced/metastatic) — inferred from clinical trial context; not formally recorded in `taiwan_regulatory`/`original_indications`
Predicted New Indication	Pulmonary Hypertension
TxGNN Prediction Score	99.03%
Evidence Level	L5
Taiwan Market Status	✗ Not Marketed
Number of Authorizations	0
Recommended Decision	Hold

Why is This Prediction Reasonable?

Detailed mechanism of action data is not available for alpelisib in this evidence pack (original_moa: [Data Gap]). Based on the retrieved literature context, alpelisib is a PI3Kα (phosphoinositide 3-kinase alpha) inhibitor used in oncology, and its efficacy in HR+/HER2-negative breast cancer is well established in the clinical trial ecosystem referenced here (e.g., the REASSURE real-world study).

The biological rationale behind the TxGNN model's high score (0.99) appears to rest on the PI3Kα/AKT/mTOR signaling pathway, which has been implicated in preclinical literature as a contributor to pulmonary vascular remodeling — a core pathological mechanism in pulmonary arterial hypertension (PAH). This shared pathway is a plausible reason the model links a breast cancer drug to a pulmonary vascular disease.

However, the actual evidence retrieved for this candidate does not support a therapeutic benefit — it points in the opposite direction. The single clinical trial identified evaluates a different drug (ribociclib) in breast cancer and has no bearing on alpelisib or pulmonary hypertension. The two literature sources describe alpelisib-induced interstitial lung disease and PI3Kα-pathway-inhibition-associated biventricular cardiac atrophy/dysfunction — both of which suggest alpelisib may pose cardiopulmonary risk in a population that already has compromised cardiopulmonary reserve (PH patients), rather than offering benefit. This is a case of a "prediction-driven, mechanism-only" signal with no clinical support and a countervailing safety signal.

Clinical Trial Evidence

Currently no clinical trials directly supporting alpelisib for pulmonary hypertension are registered.

(One trial, NCT06705504, was retrieved by the search but excluded — it is a retrospective real-world study of ribociclib and alpelisib in HR+/HER2-negative breast cancer patients, unrelated to alpelisib or pulmonary hypertension; graded "C — not relevant" in the evidence review.)

Literature Evidence

PMID	Year	Type	Journal	Key Findings
35730191	2023	Case Report	Journal of Oncology Pharmacy Practice	Reports a case of alpelisib-induced interstitial lung disease (progressive pulmonary fibrosis) in a patient being treated for advanced breast cancer — a safety signal, not efficacy evidence, for pulmonary indications
31039672	2019	Preclinical/Translational	Journal of the American Heart Association	Preclinical study showing PI3Kα pathway inhibition (the mechanistic class alpelisib belongs to) causes distinct biventricular cardiac atrophy, remodeling, and right ventricular dysfunction — right ventricular dysfunction is a key concern in pulmonary hypertension management

Taiwan Market Information

Alpelisib is currently not marketed in Taiwan — taiwan_regulatory.total_licenses = 0, and no authorization records are available in the evidence pack.

Cytotoxicity

(Included because alpelisib is an oncology agent per its known clinical use context in the retrieved trial evidence.)

Item	Content
Cytotoxicity Classification	Targeted therapy (PI3Kα inhibitor) — not a conventional cytotoxic chemotherapy agent, based on available context
Myelosuppression Risk	No myelosuppression data available in this evidence pack — please refer to the package insert
Emetogenicity Classification	No data available in this evidence pack — please refer to the package insert
Monitoring Items	Beyond routine CBC/liver/renal monitoring, the retrieved literature signals suggest pulmonary function/imaging surveillance (risk of interstitial lung disease) and cardiac function monitoring (risk of biventricular atrophy/right ventricular dysfunction) warrant attention
Handling Protection	Oral small-molecule targeted therapy; no cytotoxic-drug handling requirement is established in this evidence pack — refer to institutional oncology drug handling policy

Safety Considerations

Please refer to the package insert for safety information.

(Note: TFDA package insert warnings and contraindications are flagged as a Blocking data gap (DG001) in this evidence pack — safety review for this candidate cannot proceed to Stage 1 until this is resolved. DDI query also returned no data.)

Conclusion and Next Steps

Decision: Hold

Rationale: This candidate rests entirely on a model prediction (Evidence Level L5) with no supporting clinical trials and no efficacy literature; the only clinical trial retrieved is unrelated, and the two available publications instead describe alpelisib-induced pulmonary and cardiac toxicity — a safety signal that runs counter to use in pulmonary hypertension. Combined with a blocking gap in TFDA safety data, this candidate does not currently meet the bar to advance past initial safety screening (S0).

To proceed, the following is needed:

TFDA package insert / safety warnings and contraindications (resolves blocking gap DG001)
Confirmed mechanism of action (MOA) documentation from DrugBank (DG002)
Dedicated preclinical or clinical studies evaluating alpelisib specifically in pulmonary hypertension models or patients
A cardiopulmonary safety monitoring plan addressing the interstitial lung disease and right ventricular dysfunction signals identified in existing literature
Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.