Trastuzumab Emtansine
| Evidence Level: L4 | Predicted Indications: 10 |
Table of Contents
- Trastuzumab Emtansine
- Trastuzumab emtansine: From HER2-Positive Breast Cancer to Progesterone-Receptor Positive Breast Cancer
Trastuzumab emtansine: From HER2-Positive Breast Cancer to Progesterone-Receptor Positive Breast Cancer
One-Sentence Summary
Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate originally used to treat HER2-positive breast cancer. The TxGNN model predicts it may be effective for progesterone-receptor positive breast cancer, but no clinical trials are registered for this entry. The 15 publications retrieved are mostly guidelines, reviews and case reports, and this prediction largely overlaps with the drug's existing approved indication rather than representing a true new use.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | HER2-positive breast carcinoma (the Singapore licence records contain no approved indication text, so this comes from the knowledge graph) |
| Predicted New Indication | Progesterone-receptor positive breast cancer |
| TxGNN Prediction Score | 99.82% |
| Evidence Level | L4 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 2 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed mechanism-of-action data are not available in the data compiled for this report. Based on known information, T-DM1 combines the antibody trastuzumab, which binds HER2, with DM1, a microtubule-inhibiting cytotoxic payload released after the conjugate is internalised by the cell. Its activity depends on HER2 expression, not on hormone receptor status.
Many tumours that are both progesterone-receptor positive and HER2-positive (HR+/HER2+ breast cancer) are therefore already within the scope of the approved HER2-positive indication. The prediction is largely an overlap with the original indication, not a true repurposing signal. Tumours that are progesterone-receptor positive but HER2-negative would not be expected to respond through this mechanism.
For context, the other predicted indications range from reasonable to unsupported:
- Progesterone-receptor negative breast cancer (score 99.82%): within the HER2-driven mechanism. One terminated Phase 2 trial is listed (see below).
- Breast tumour, luminal A or B (score 99.81%): plausible only for HER2-positive luminal B tumours. Luminal A tumours are generally HER2-negative.
- Normal breast-like subtype, synovium cancer, tenosynovial giant cell tumour (including the localised type), malignant giant cell tumour, HHV-8-related tumour and ectomesenchymoma: no HER2-dependent mechanism and no supporting clinical evidence. These are computational predictions only and are recommended to be held.
Clinical Trial Evidence
Currently no related clinical trials registered for progesterone-receptor positive breast cancer.
For the related prediction of progesterone-receptor negative breast cancer, one trial is listed:
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT04675827 | Phase 2 | Terminated | 139 | DECRESCENDO: single-arm de-escalation study in HER2-positive, ER-negative, node-negative early breast cancer after neoadjuvant chemotherapy with dual HER2 blockade. Terminated, so unlikely to give conclusive efficacy evidence. |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 35640077 | 2022 | Guideline | J Clin Oncol | ASCO guideline update on systemic therapy for advanced HER2-positive breast cancer |
| 24799465 | 2014 | Guideline | J Clin Oncol | ASCO clinical practice guideline on systemic therapy for advanced HER2-positive breast cancer |
| 29939838 | 2018 | Guideline | J Clin Oncol | ASCO guideline update, 2018, based on a systematic review of 622 articles |
| 28259011 | 2017 | Guideline | Eur J Cancer | EGTM biomarker guidelines. HER2 testing is mandatory to select patients for anti-HER2 therapy, including T-DM1. ER and PR testing guides endocrine therapy. |
| 33726508 | 2021 | Review | Future Oncol | Trends in HR+/HER2+ breast cancer. Hormone plus anti-HER2 combinations without chemotherapy give long-term control in some patients. Neratinib and T-DM1 are discussed. |
| 39631485 | 2024 | Review | Pharmacol Res | Targeted and cytotoxic inhibitors in breast cancer, organised by HER2, HR, ER and PR status |
| 24892840 | 2013 | Review | Clin Adv Hematol Oncol | Metastatic breast cancer developments, by receptor subtype |
| 34215766 | 2021 | Cohort (real-world) | Sci Rep | ChangeHER: prognostic relevance of gaining HER2 positivity in metastatic disease, in patients treated with pertuzumab and/or T-DM1 |
| 25873876 | 2015 | Case report | Case Rep Oncol | Dose-reduced T-DM1 was active and safe in a patient with acute hepatic dysfunction |
| 33482449 | 2021 | Case report | Int J Surg Case Rep | Metastatic breast cancer in a patient on haemodialysis |
None of these is a randomised trial of T-DM1 in progesterone-receptor positive disease. All are indirect evidence.
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN14497P | KADCYLA powder for concentrate for solution for infusion 100 mg/vial | Injection, powder, for solution | Not stated in the licence record |
| SIN14496P | KADCYLA powder for concentrate for solution for infusion 160 mg/vial | Injection, powder, for solution | Not stated in the licence record |
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Antibody-drug conjugate (HER2-targeted antibody linked to a microtubule-inhibiting cytotoxic payload, DM1) |
| 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. Haematological parameters, liver function and renal function are standard for cytotoxic therapy. |
| Handling Protection | Follow institutional cytotoxic drug handling regulations |
Safety Considerations
- Drug Interactions: The interaction screen returned 100 interacting drugs in total. Examples include:
- Major: acetylsalicylic acid, deferasirox, and several antithrombotic or anticoagulant agents (abciximab, apixaban, argatroban, betrixaban, bivalirudin, cangrelor, caplacizumab, cilostazol). These are consistent with a bleeding-risk concern when combined with agents that affect clotting.
- Moderate: clarithromycin, metronomidazole, tinidazole, naltrexone, rosuvastatin, simvastatin, cobicistat, and the appetite-suppressant agents fenfluramine, dexfenfluramine and sibutramine.
Package insert warnings and contraindications were not available for this report. Please refer to the package insert for further safety information.
Conclusion and Next Steps
Decision: Hold
Rationale: The model score is high (99.82%), but there are no registered trials for this indication, and the supporting literature consists of guidelines, reviews and case reports. The plausible use is HR+/HER2+ disease, which falls inside the already approved HER2-positive indication, so this is not a new-use finding. Several other predictions (synovium cancer, tenosynovial giant cell tumours, HHV-8-related tumours, ectomesenchymoma) have no mechanistic or clinical support.
To proceed, the following is needed:
- Confirmation of the approved indication wording from the Singapore package insert, to check whether HR+/HER2+ disease is already covered
- Package insert warnings and contraindications, which are currently missing and block safety screening
- Detailed mechanism-of-action data
- Direct clinical data (trial results or subgroup analyses) for T-DM1 in HR+/HER2+ breast cancer
- Re-framing of the question toward a genuinely new setting, for example HER2-low or HER2-mutant disease, rather than hormone receptor subtypes
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.