Ramucirumab
| Evidence Level: L5 | Predicted Indications: 10 |
Table of Contents
Ramucirumab: From Lung, Gastric and Liver Cancers to Uterine Ligament Adenocarcinoma
One-Sentence Summary
Ramucirumab is a monoclonal antibody that blocks VEGFR2. It was originally used for cancers such as gastric adenocarcinoma, non-small cell lung carcinoma and hepatocellular carcinoma. The TxGNN model predicts it may be effective for uterine ligament adenocarcinoma, but there are currently 0 clinical trials and 0 publications supporting this direction, so the prediction rests on the model score alone.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Non-small cell lung carcinoma, gastric adenocarcinoma, hepatocellular carcinoma (the Singapore licence records contain no indication text; these come from the knowledge graph) |
| Predicted New Indication | Uterine ligament adenocarcinoma |
| TxGNN Prediction Score | 99.95% |
| Evidence Level | L5 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 2 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism of action data is not available in the data compiled for this report. Based on known drug class information, ramucirumab is a VEGFR2-blocking antibody that inhibits tumour angiogenesis. Its efficacy in gastric, lung and liver cancers is established, and mechanistically it may be applicable to other angiogenesis-dependent adenocarcinomas.
Adenocarcinomas of gynaecological origin are generally angiogenesis-dependent, so a VEGFR2-mediated rationale is plausible. However, this link is inferred only from the TxGNN score (0.9995) and class-level reasoning. No trial or literature data were available for this specific entity.
Other high-ranking predictions are mostly gynaecological adenocarcinomas, mainly cervical and uterine ligament subtypes. They include endocervical carcinoma (99.95%), adenoid cystic carcinoma of the cervix uteri (99.95%) and several uterine ligament histologic variants. Two of them, signet ring cell variant cervical mucinous adenocarcinoma and intestinal variant cervical mucinous adenocarcinoma, bear a loose histologic resemblance to gastrointestinal adenocarcinomas. The high scores may partly reflect ontology proximity between related cervical and adenocarcinoma terms rather than disease-specific biology.
Clinical Trial Evidence
Currently no related clinical trials registered.
Literature Evidence
Currently no related literature available.
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN15036P | CYRAMZA Concentrate for Solution for Infusion 500mg/50mL | Injection, solution, concentrate | Not stated in the available records |
| SIN15035P | CYRAMZA Concentrate for Solution for Infusion 100mg/10mL | Injection, solution, concentrate | Not stated in the available records |
Both licences are valid single-ingredient products. The manufacturers are Eli Lilly and Company and Lilly France (Fegersheim).
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Targeted therapy (anti-VEGFR2 monoclonal antibody), not a conventional cytotoxic |
| Myelosuppression Risk | Please refer to the package insert warnings and precautions |
| Emetogenicity Classification | Please refer to the package insert warnings and precautions |
| Monitoring Items | Please refer to the package insert warnings and precautions |
| Handling Protection | Please refer to the package insert warnings and precautions |
Safety Considerations
- Drug Interactions: The interaction screen returned 100 interactions in total. The first 20 returned include 1 involving acetylsalicylic acid and 3 involving fenfluramine-type agents (dexfenfluramine, fenfluramine and sibutramine) at Moderate level, and many at Major level. The main groups are:
- Antithrombotics and anticoagulants (Major): acetylsalicylic acid, abciximab, alteplase, antithrombin III human, apixaban, betrixaban, bivalirudin, cangrelor, caplacizumab, cilostazol, clopidogrel, dalteparin and defibrotide. These raise concern about additive bleeding risk.
- Radiolabelled antibodies (Major): ibritumomab tiuxetan, tositumomab and tositumomab (I-131).
- Other (Major): deferasirox.
- Appetite suppressants (Moderate): dexfenfluramine, fenfluramine and sibutramine.
Please refer to the package insert for key warnings and contraindications.
Conclusion and Next Steps
Decision: Hold
Rationale: The prediction is supported only by the model score (L5), with no clinical trials or publications for uterine ligament adenocarcinoma or any of the other predicted gynaecological entities. The mechanistic argument is class-level reasoning rather than disease-specific evidence, and the package insert safety data have not yet been obtained.
To proceed, the following is needed:
- Package insert warnings and contraindications from the HSA website, including the approved indication text
- Detailed mechanism of action data from DrugBank
- A literature and trial search for ramucirumab in gynaecological adenocarcinomas, particularly cervical and uterine ligament tumours
- Assessment of whether the rare uterine ligament histologic subtypes are clinically meaningful targets, or whether a better-studied gynaecological indication should be prioritised
- Review of bleeding risk in patients taking antithrombotic or anticoagulant agents
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.