Ribociclib
| Evidence Level: L4 | Predicted Indications: 4 |
Table of Contents
- Ribociclib
- Pharmacist Assessment Report
- Ribociclib: From HR+/HER2- Breast Cancer to Myeloid Leukaemia
- One-Sentence Summary
- Quick Overview
- Why is This Prediction Reasonable?
- Clinical Trial Evidence
- Literature Evidence
- Australia Market Information
- Cytotoxicity
- Safety Considerations
- Conclusion and Next Steps
- Disclaimer
Ribociclib: From HR+/HER2- Breast Cancer to Myeloid Leukaemia
One-Sentence Summary
Ribociclib (Kisqali) is an oral CDK4/6 inhibitor used for hormone receptor-positive, HER2-negative breast cancer. The TxGNN model predicts it may be effective for myeloid leukaemia, but the data compiled for this report contain no registered clinical trials and only 1 relevant preclinical publication for this indication, so the prediction remains unvalidated.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | HR+/HER2- breast cancer (the ARTG entry in the data carries no indication text; this is taken from the trials and literature) |
| Predicted New Indication | Myeloid leukaemia |
| TxGNN Prediction Score | 0.9935 |
| Evidence Level | L4 |
| Australia Market Status | Listed on the PBS Schedule (1 of 1 items) – TGA (ARTG) registration status is not included in this data |
| Number of PBS Items | 1 (valid: 1) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data are not available in the compiled data. Ribociclib belongs to the selective CDK4/6 inhibitor class. In breast cancer these drugs block Rb phosphorylation and G1-to-S cell cycle progression. Their efficacy there is well established in Phase 3 trials (MONALEESA-2, -3 and -7, and NATALEE).
Mechanistically, CDK4/6 signalling is thought to drive proliferation in acute myeloid leukaemia (AML), so the prediction is biologically plausible. A 2020 preclinical paper (PMID 32560251) reports that CDK4/6 inhibitors can target pharmacokinetic drug resistance in AML cells. This resistance is linked to ABCB1/ABCG2 transporter overexpression and anthracycline metabolism. This is indirect, in vitro evidence only. It does not show that ribociclib treats leukaemia in patients.
Clinical Trial Evidence
Currently no related clinical trials registered for myeloid leukaemia.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 32560251 | 2020 | Preclinical (in vitro) | Cancers | CDK4/6 inhibitors may target pharmacokinetic drug resistance in AML cells (ABCB1/ABCG2 transporters and anthracycline biotransformation) |
| 41641105 | 2026 | Case report | Frontiers in Oncology | Vulvar adenocarcinoma in a patient with breast cancer. Not relevant to leukaemia and should not be counted as supporting evidence |
Australia Market Information
| ARTG Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 11385F | Kisqali | Tablet 200 mg (oral) | Not stated in the data compiled |
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Targeted therapy (CDK4/6 inhibitor) |
| Myelosuppression Risk | Notable. Neutropenia is the key haematological toxicity, and thrombocytopenia and anaemia are also reported. This is especially relevant in a haematological malignancy, where marrow function is already compromised |
| Emetogenicity Classification | Please refer to the Product Information (PI) |
| Monitoring Items | FBC with differential, liver function tests, electrolytes and ECG (QTc) |
| Handling Protection | Please refer to the PI and local cytotoxic or hazardous drug handling policies |
Safety Considerations
- Drug Interactions: The interaction query returned 100 entries. Two are rated Major: clarithromycin and dolasetron. Many are rated Moderate, including corticosteroids (dexamethasone, hydrocortisone, budesonide, betamethasone, triamcinolone), metformin, pioglitazone, saxagliptin, cimetidine, famotidine, aprepitant and loperamide. The published literature describes ribociclib’s metabolism via CYP3A4 as a high-risk pathway for interactions.
- Other signals from the literature: QT prolongation and arrhythmia, hepatotoxicity (raised transaminases), pneumonitis, thromboembolic events, and haematological toxicity.
Please refer to the TGA-approved Product Information (PI) for full warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale:
- The only supporting evidence for myeloid leukaemia is a single in vitro study. There are no registered trials and no clinical data. Ribociclib’s myelosuppressive profile is also a particular concern in a marrow-based malignancy.
- Other top-ranked TxGNN predictions for ribociclib (thrombocytopenia and related platelet disorders) appear to be artefacts of the drug’s adverse-event profile and are not credible treatment targets. The breast carcinoma prediction is simply the existing approved use.
To proceed, the following is needed:
- In vivo and further in vitro studies of ribociclib in AML and other myeloid models
- Mechanism of action data (MOA) and a clear rationale for combination partners
- A safety assessment of myelosuppression, QT prolongation and CYP3A4 interactions in patients with leukaemia
- The full TGA Product Information (warnings, contraindications and approved indication text)
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.