Trabectedin
| Evidence Level: L5 | Predicted Indications: 1 |
Table of Contents
- Trabectedin
- Pharmacist Assessment Report
- Trabectedin: From Ovarian Cancer to Female Breast Carcinoma
- One-Sentence Summary
- Quick Overview
- Why is This Prediction Reasonable?
- Clinical Trial Evidence
- Literature Evidence
- India Market Information
- Cytotoxicity
- Safety Considerations
- Conclusion and Next Steps
- Disclaimer
Trabectedin: From Ovarian Cancer to Female Breast Carcinoma
One-Sentence Summary
Trabectedin is a marine-derived DNA-binding cytotoxic drug, originally used to treat ovarian cancer (and, in Europe, soft tissue sarcoma). The TxGNN model predicts it may be effective for Female Breast Carcinoma, with 1 clinical trial (a safety-focused QT study) and 20 publications currently related to this direction. Published single-agent Phase 2 breast cancer data show only modest activity.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Ovarian cancer (including ovarian adenocarcinoma, clear cell, endometrioid and mucinous subtypes, and related germ cell tumours) |
| Predicted New Indication | Female breast carcinoma |
| TxGNN Prediction Score | 0.9973 |
| Evidence Level | L5 |
| India Market Status | Listed in a compiled Indian medicine price dataset (1 of 1) – CDSCO approval status is not included in this data |
| Number of Listed Products | 1 (valid: 1) |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Trabectedin binds the minor groove of DNA and causes DNA damage. It interferes with transcription and DNA-repair machinery. It is particularly active in cells with deficient homologous recombination repair, such as BRCA1/2-deficient tumours. Formal mechanism-of-action data were not available in the data compiled for this report, so this description draws on the published literature.
Ovarian and breast cancers share DNA-repair biology, especially in BRCA-associated disease and triple-negative breast cancer. Trabectedin also reduces tumour-associated macrophages and modulates the tumour microenvironment. Preclinical work suggests it enhances the antitumour effect of IL-12 in triple-negative breast cancer.
The high TxGNN score is a model prediction, not clinical proof. Published single-agent Phase 2 data in anthracycline- and taxane-pretreated advanced breast cancer show only modest activity, so efficacy in breast cancer remains unestablished.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00786838 | Phase 2 | Completed | 76 | Single-blind, placebo-controlled study of trabectedin’s effect on QT interval in advanced solid tumours. It addresses cardiac safety, not breast cancer efficacy, so it gives limited support |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 25239225 | 2014 | Phase 2 randomised study | Clin Breast Cancer | Compared two trabectedin regimens as a single agent in advanced breast cancer after anthracycline and taxane treatment |
| 24692579 | 2014 | Phase 2 trial | Ann Oncol | Efficacy and safety in pretreated metastatic breast cancer with germline BRCA1/2 mutations |
| 27266804 | 2016 | Phase 2 trial | Clin Breast Cancer | Trabectedin in HR-positive, HER2-negative advanced breast cancer, by XPG gene expression |
| 19114300 | 2009 | Phase 1 trial | Eur J Cancer | Trabectedin plus doxorubicin in 38 patients (29 sarcoma, 9 breast); feasibility and activity, mostly in sarcoma |
| 26592307 | 2016 | Review | Expert Opin Investig Drugs | Overview of trabectedin in breast cancer, including its microenvironment effects |
| 27710871 | 2016 | Review | Cancer Treat Rev | Trabectedin as a chemotherapy option in BRCA-deficient tumours |
| 39777457 | 2025 | Preclinical | Cancer Immunol Res | Trabectedin enhances IL-12 antitumour effects in triple-negative breast cancer |
| 24941346 | 2014 | Preclinical | Eur Cytokine Netw | Anti-angiogenic effects on human breast cancer cells |
| 23792433 | 2013 | Preclinical | Toxicol Lett | Apoptosis induction in MCF-7 and MDA-MB-453 breast cancer cells |
| 25722380 | 2015 | Exploratory analysis of Phase 3 | Ann Oncol | Effect of BRCA1 and XPG mutations on response to trabectedin plus PLD in ovarian cancer (OVA-301) |
India Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 217905 | Trabec 1mg Solution for Infusion (Natco Pharma Ltd) | Vial of 1 solution for infusion | Not specified in the registration data |
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Conventional cytotoxic (DNA minor-groove alkylating agent, marine-derived) |
| Myelosuppression Risk | High (literature reports grade 3-4 neutropenia in about 50% and thrombocytopenia in about 20% of patients) |
| Emetogenicity Classification | Please refer to the package insert warnings and precautions |
| Monitoring Items | CBC with differential, liver function (hepatic toxicity is reported), renal function; consider cardiac monitoring given the QT study |
| Handling Protection | Must follow cytotoxic drug handling regulations |
Safety Considerations
- Drug Interactions: 450 interactions were identified. Among those listed, clarithromycin is rated Major. Moderate interactions include aprepitant, dexamethasone, cimetidine, metronidazole, miconazole, levofloxacin, minocycline, bupropion, naltrexone, rosuvastatin and simvastatin. Several others are also listed, including antidiabetic agents (acarbose, pioglitazone, rosiglitazone). The full list should be reviewed before any clinical use.
Please refer to the package insert for other safety information (warnings and contraindications).
Conclusion and Next Steps
Decision: Hold
Rationale: The mechanism is plausible, especially for BRCA-deficient and triple-negative breast cancer, and the TxGNN score is high. However, the only registered trial is a QT safety study, and published single-agent Phase 2 data show modest activity. There is no completed Phase 3 evidence in breast cancer. This is best treated as a research question rather than a candidate for advancing.
To proceed, the following is needed:
- Package insert warnings and contraindications from the India registration (currently a blocking gap for safety screening)
- Approved indication text for the Indian registration
- Detailed mechanism-of-action data from DrugBank
- Full review of the Phase 2 breast cancer results (PMIDs 25239225, 24692579, 27266804), focusing on BRCA-mutated and triple-negative subgroups
- A biomarker-driven trial design (e.g., BRCA or XPG status) if development continues
- Review of the clarithromycin and other drug interactions for the proposed patient population
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.