Trastuzumab
| Evidence Level: L5 | Predicted Indications: 6 |
Table of Contents
Trastuzumab: Malignant cutaneous granular cell skin tumor
One-Sentence Summary
Trastuzumab is a HER2-targeted monoclonal antibody, originally used to treat HER2-positive breast carcinoma. This is largely a subtype of the already established HER2-positive breast cancer indication, so the repurposing novelty is low even though the evidence is strong.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not recorded in the local data |
| Predicted New Indication | Malignant cutaneous granular cell skin tumor |
| TxGNN Prediction Score | 0.9948 |
| Evidence Level | L5 |
| India Market Status | Listed in a compiled Indian medicine price dataset (at least 20) – CDSCO approval status is not included in this data |
| Number of Listed Products | at least 20 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Currently, detailed mechanism of action data is not available in the data compiled for this report. Based on known pharmacology, trastuzumab binds HER2 and blocks its signalling. Its established effects include antibody-dependent cellular cytotoxicity (ADCC) and inhibition of downstream PI3K/AKT signalling.
HER2-positive breast cancer frequently co-occurs with hormone receptor (progesterone/estrogen receptor) positivity. Patients with PR-positive, HER2-positive tumours therefore fall within the population already treated with trastuzumab. Combining HER2 blockade with endocrine therapy is a recognised strategy in this group.
This should be viewed as an approved-indication subtype rather than a truly new indication. Benefit is expected only in confirmed HER2-positive patients. PR-positive tumours that are HER2-negative (for example luminal A) are not expected to respond.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT01275677 | Phase 3 | Completed | 3270 | Adjuvant chemotherapy with vs without trastuzumab in node-positive or high-risk node-negative breast cancer; the most direct Phase 3 evidence |
| NCT01750073 | Phase 2 | Completed | 92 | Neoadjuvant paclitaxel and cyclophosphamide with or without trastuzumab |
| NCT00194779 | Phase 2 | Completed | 50 | Neoadjuvant chemotherapy regimen followed by a trastuzumab-containing regimen in HER2-positive breast cancer |
| NCT02260531 | Phase 2 | Completed | 36 | Cabozantinib alone or with trastuzumab in breast cancer with brain metastases; small and exploratory |
| NCT00134680 | Phase 2 | Completed | 33 | Letrozole plus trastuzumab in ErbB2-positive, ER and/or PR-positive metastatic breast cancer |
| NCT04886531 | Phase 2 | Recruiting | 30 | Pre-operative neratinib, endocrine therapy and trastuzumab in ER-positive, HER2-positive cancers |
| NCT04334330 | Phase 2 | Unknown | 34 | Palbociclib, trastuzumab, pyrotinib and fulvestrant in ER/PR-positive, HER2-positive brain metastases; trastuzumab effect cannot be isolated |
| NCT02152943 | Phase 1 | Completed | 37 | Everolimus, letrozole and trastuzumab in hormone receptor-positive, HER2-positive advanced cancers |
| NCT04629846 | Phase 3 | Completed | 517 | Pertuzumab biosimilar QL1209 with trastuzumab and docetaxel in HER2-positive, ER/PR-negative breast cancer; limited relevance to PR-positive disease |
| NCT05868226 | Phase 1/2 | Recruiting | 280 | Platform trial on response prediction; indirect |
Note: NCT00053339, a Phase 3 trial of trastuzumab with or without tamoxifen, was withdrawn with no participants enrolled and provides no evidence.
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 27179402 | 2016 | RCT | Lancet Oncol | NeoSphere 5-year analysis: neoadjuvant pertuzumab plus trastuzumab in HER2-positive breast cancer |
| 32353342 | 2020 | RCT | Lancet Oncol | monarcHER: abemaciclib plus trastuzumab with or without fulvestrant in HR-positive, HER2-positive advanced breast cancer |
| 28945833 | 2017 | RCT | Ann Oncol | WSG-ADAPT HER2+/HR-: de-escalation with dual HER2 blockade |
| 26874901 | 2016 | RCT | Lancet Oncol | ExteNET: neratinib after trastuzumab-based adjuvant therapy |
| 29117498 | 2017 | Meta-analysis | N Engl J Med | 20-year recurrence risk after stopping endocrine therapy in ER-positive early breast cancer |
| 15894097 | 2005 | Meta-analysis | Lancet | Overview of randomised trials of chemotherapy and hormonal therapy in early breast cancer |
| 31410192 | 2019 | Multi-cohort analysis | Theranostics | Molecular features and trastuzumab responsiveness of ER+/PR+/HER2+ (triple-positive) breast cancer |
| 21151204 | 2011 | Review | Nat Rev Clin Oncol | HER2 and hormone receptor-positive breast cancer: aromatase inhibitors with anti-HER2 therapy |
| 33726508 | 2021 | Review | Future Oncol | Current trends in HR+/HER2+ treatment, including chemotherapy-free combinations |
| 35640077 | 2022 | Guideline | J Clin Oncol | ASCO guideline update on systemic therapy for advanced HER2-positive breast cancer |
India Market Information
Trastuzumab has 20 valid single-ingredient registrations in India and no cancelled ones. The data compiled for this report did not include approved indication text for any of them. The first five are listed below.
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| 73635 | Eleftha 150mg Injection (Intas) | Vial of 1 injection | Not stated in compiled data |
| 105738 | Herticad 440mg Injection (Sayre Therapeutics) | Vial of 1 injection | Not stated in compiled data |
| 217215 | Trumab Injection (Glenmark) | Vial of 1 powder for infusion | Not stated in compiled data |
| 105410 | Hersima 150mg Injection (Alkem) | Vial of 1 injection | Not stated in compiled data |
| 164987 | Ontramab 440mg Injection (Celon) | Vial of 1 injection | Not stated in compiled data |
Cytotoxicity
Trastuzumab is a targeted antibody therapy used in oncology rather than a conventional cytotoxic chemotherapy.
| Item | Content |
|---|---|
| Cytotoxicity Classification | Targeted therapy (HER2-directed monoclonal antibody) |
| Myelosuppression Risk | Please refer to the package insert warnings and precautions (often combined with myelosuppressive chemotherapy) |
| Emetogenicity Classification | Low as a single agent; overall regimen depends on the combined chemotherapy |
| Monitoring Items | Cardiac function (LVEF) before and during treatment; CBC and liver and renal function when combined with chemotherapy |
| Handling Protection | Please refer to the package insert and local institutional policy for handling of antineoplastic agents |
Safety Considerations
- Drug Interactions: 94 interactions were identified in the compiled interaction data. Examples of the Major level include deferiprone, samarium (153Sm) lexidronam, adalimumab and baricitinib. Moderate examples include paclitaxel, warfarin, dicoumarol, alemtuzumab, azathioprine, zidovudine, chloramphenicol and several vaccines (tetanus toxoid, anthrax).
- Cardiac toxicity: The literature compiled for this report (PMID 17687157) discusses trastuzumab-related cardiotoxicity and questions whether it is fully reversible. Cardiac monitoring is therefore an important consideration.
Warnings and contraindications from the package insert were not available. Please refer to the package insert for full safety information.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: A completed Phase 3 RCT (NCT01275677, n=3270) and multiple randomised studies support trastuzumab-based treatment in HER2-positive breast cancer, which includes PR-positive patients. Because this is a subtype of an already approved indication, benefit applies only to confirmed HER2-positive disease.
To proceed, the following is needed:
- Restrict use to confirmed HER2-positive patients; there is no support for HER2-negative PR-positive disease
- Package insert warnings and contraindications from the Indian regulator (currently missing)
- Detailed mechanism of action data
- A cardiac monitoring plan (baseline and periodic LVEF assessment)
- Review of the Major drug interactions before combination use
- Dedicated evidence for the PR-positive/HER2-positive subgroup, since the Phase 3 trial data mainly cover the broader HER2-positive population
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.