Osimertinib
| Evidence Level: L4 | Predicted Indications: 10 |
Table of Contents
Osimertinib: From EGFR-Mutant Non-Small Cell Lung Cancer to Thrombocytopenia
One-Sentence Summary
Osimertinib is an oral EGFR tyrosine kinase inhibitor marketed in Singapore as Tagrisso. The TxGNN model predicts it for thrombocytopenia with a very high score, but no clinical trials and only literature describing osimertinib as a cause of low platelets support it. This looks like an adverse-event signal rather than a therapeutic opportunity.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not stated in the Singapore licence data (the literature describes it as an EGFR-TKI for EGFR-mutant non-small cell lung cancer) |
| Predicted New Indication | Thrombocytopenia |
| TxGNN Prediction Score | 98.46% |
| Evidence Level | L4 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 2 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available. Based on the literature, osimertinib is a third-generation, irreversible EGFR tyrosine kinase inhibitor used for EGFR-mutant non-small cell lung cancer (NSCLC), including T790M-positive disease.
The prediction does not appear to be mechanistically reasonable. The literature describes osimertinib as a cause of thrombocytopenia: a meta-analysis of randomised trials reports haematological toxicity, and case reports describe severe thrombocytopenia, including one with rechallenge. No plausible mechanism is identified by which EGFR inhibition would raise platelet counts. The high TxGNN score most likely reflects a drug-disease association in the knowledge graph, not a therapeutic effect.
The other top predictions show the same pattern. Heart neoplasm, thrombotic disease, heart conduction disease, cardiovascular disease and heart disease are all supported mainly by osimertinib's cardiac and thrombotic adverse events, such as cardiomyopathy, heart failure, QT prolongation and thrombosis. The remaining rare platelet and haematological conditions (marcothrombocytopenia with mitral valve insufficiency, hereditary thrombocytopenia with normal platelets, transient neonatal thrombocytopenia, dense granule disease) have no trials or literature at all.
Clinical Trial Evidence
Currently no related clinical trials registered for thrombocytopenia.
For context, trials linked to other predicted indications (heart neoplasm, cardiovascular disease, heart disease) are oncology studies that do not test osimertinib for those conditions:
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT03989115 | Phase 1/2 | Completed | 113 | RMC-4630 with cobimetinib in solid tumours, and RMC-4630 with osimertinib in EGFR-mutant NSCLC; safety and dosing |
| NCT04959981 | Phase 1 | Completed | 24 | MAPK-pathway agents (ERAS-007/ERAS-601) with other therapies in advanced NSCLC |
| NCT06303167 | Phase 2 | Active, not recruiting | 19 | NCI-MATCH subprotocol E: osimertinib in tumours with EGFR T790M or rare activating mutations |
| NCT02465060 | Phase 2 | Active, not recruiting | 6452 | NCI-MATCH umbrella trial of genetically directed therapy in refractory solid tumours |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 39159992 | 2024 | Meta-analysis of RCTs | BMJ Support Palliat Care | Quantifies osimertinib-related haematological toxicity in NSCLC |
| 40135231 | 2025 | Network meta-analysis / pharmacovigilance | Front Pharmacol | Adverse-event profiles of EGFR-TKIs |
| 36729978 | 2023 | Case report | Anti-Cancer Drugs | Severe thrombocytopenia with osimertinib plus sitagliptin; successful rechallenge after recovery |
| 36730569 | 2023 | Case report | Anti-Cancer Drugs | Osimertinib-induced severe thrombocytopenia; switched to aumolertinib |
| 40115544 | 2025 | Case report | Case Rep Oncol | Thrombocytopenia in EGFR-mutant lung adenocarcinoma with ARDS treated with ECMO and osimertinib |
| 33755621 | 2021 | News/nursing summary | Am J Nurs | Lists thrombocytopenia among common adverse effects of adjuvant osimertinib |
| 34491978 | 2021 | Case report | Am J Case Rep | Osimertinib-induced erythrocytosis with arterial thrombosis; thrombocytopenia noted as a known haematological adverse effect |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN15139P | TAGRISSO TABLET 80MG | Tablet, film coated | Not stated in the licence data |
| SIN15140P | TAGRISSO TABLET 40MG | Tablet, film coated | Not stated in the licence data |
Both licences are held by AstraZeneca AB, are single-ingredient products, and are currently valid. The only dosage form is oral.
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Targeted therapy (EGFR tyrosine kinase inhibitor) |
| Myelosuppression Risk | Low to medium; leukopenia, lymphopenia, thrombocytopenia, anaemia and neutropenia are reported, and severe thrombocytopenia is rare |
| Emetogenicity Classification | Low |
| Monitoring Items | CBC with differential (especially platelets), liver and renal function, ECG/QT and cardiac function (LVEF) |
| Handling Protection | Please refer to the package insert warnings and precautions |
Safety Considerations
- Drug Interactions: 100 interactions were identified. The major-level ones among those listed include clarithromycin, dolasetron, palonosetron and levofloxacin. Several moderate interactions were also listed, for example famotidine, cimetidine, dexamethasone, aprepitant, loperamide, empagliflozin and miconazole. A reported case of severe thrombocytopenia occurred when osimertinib was combined with sitagliptin.
- Literature safety signals: Cardiotoxicity (cardiomyopathy, heart failure, QT prolongation, atrial fibrillation), thrombotic events (pulmonary embolism, arterial thrombosis), interstitial lung disease and haematological toxicity are reported.
Package insert warnings and contraindications were not available for this report; please refer to the package insert.
Conclusion and Next Steps
Decision: Hold
Rationale: The high TxGNN score for thrombocytopenia is driven by osimertinib causing the condition, not treating it. There are no supporting trials, no plausible mechanism, and the cardiac and thrombotic predictions point to risk rather than benefit.
To proceed, the following is needed:
- Singapore package insert warnings, contraindications and approved indication text
- Detailed mechanism of action data
- Any prospective evidence that osimertinib improves platelet counts (none was found, so reconsideration is unlikely without it)
- If the interest is in the safety signals, a separate pharmacovigilance and monitoring review (platelets, cardiac function, QT) rather than a repurposing assessment
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.