Talazoparib
| Evidence Level: L2 | Predicted Indications: 10 |
Table of Contents
- Talazoparib
- Talazoparib: From Its Approved Use in BRCA-Mutated Breast Cancer to HER2-Positive Breast Carcinoma
Talazoparib: From Its Approved Use in BRCA-Mutated Breast Cancer to HER2-Positive Breast Carcinoma
One-Sentence Summary
Talazoparib (Talzenna) is an oral PARP inhibitor, and the Singapore licence records compiled for this report do not list an approved indication text. The TxGNN model predicts it may be effective for HER2-positive breast carcinoma, with 6 related clinical trials and 14 publications linked to this prediction. None of these is specific to HER2-positive disease, so the support is indirect.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not stated in the Singapore licence records (published literature describes use in germline BRCA-mutated, HER2-negative breast cancer) |
| Predicted New Indication | HER2 positive breast carcinoma |
| TxGNN Prediction Score | 98.98% |
| Evidence Level | L2 |
| Singapore Market Status | ✓ Marketed |
| Number of Registrations | 2 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Detailed mechanism-of-action data is not available in the compiled drug record. From the supporting analysis, talazoparib is a PARP1/2 inhibitor. It traps PARP on DNA and causes synthetic lethality in cells with homologous recombination deficiency (HRD), such as those with BRCA1/2 mutations.
The drug's established use in the literature is germline BRCA-mutated, HER2-negative breast cancer (based on the EMBRACA trial). For HER2-positive disease the link is indirect. It depends on a tumour's BRCA/HRD status, not on HER2 biology. Several Phase 2 trials enrol mixed breast cancer populations, but none appears specific to HER2-positive disease. The prediction is therefore best read as "talazoparib may help the BRCA/HRD-positive subset of HER2-positive patients", not as a broad HER2-positive claim.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT05826964 | Phase 2 | Active, not recruiting | 24 | ctDNA-guided early treatment switch in metastatic breast cancer; HER2-positive relevance unclear |
| NCT04550494 | Phase 2 | Active, not recruiting | 29 | Talazoparib in advanced solid tumours with DNA damage response gene aberrations; not breast-specific |
| NCT01042379 | Phase 2 | Recruiting | 5000 | I-SPY2 adaptive platform in high-risk early breast cancer, including HER2-positive patients; talazoparib is one of many arms |
| NCT03911973 | Phase 1/2 | Active, not recruiting | 37 | Gedatolisib plus talazoparib in triple-negative or BRCA-mutated, HER2-negative breast cancer |
| NCT03499353 | Phase 2 | Terminated | 61 | Neoadjuvant talazoparib in germline BRCA-mutated, HER2-negative early breast cancer; stopped early |
| NCT04134884 | Phase 1 | Completed | 34 | ASTX727 plus talazoparib safety study in triple-negative or HER2-negative metastatic breast cancer |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 36379199 | 2022 | Meta-analysis | Breast | PARP inhibitors (olaparib, talazoparib) in BRCA1/2-related advanced HER2-negative breast cancer, with GRADE recommendations |
| 36202026 | 2022 | Network meta-analysis | Cancer Treat Rev | Therapeutic sequencing in metastatic triple-negative breast cancer |
| 36045677 | 2022 | Retrospective comparative study | Front Immunol | Talazoparib versus conventional chemotherapy; the abstract describes HER2-negative advanced breast cancer, so its direct bearing on HER2-positive disease is unclear |
| 36952230 | 2023 | Real-world cohort | The Oncologist | Real-world use of talazoparib in germline BRCA-mutated, HER2-negative advanced breast cancer |
| 34324367 | 2021 | Guideline (review) | J Clin Oncol | ASCO update on endocrine and targeted therapy for HR-positive, HER2-negative metastatic breast cancer |
| 35343197 | 2022 | Review | Indian J Cancer | Role of PARP inhibitors in HER2-negative metastatic breast cancer |
| 33983696 | 2021 | Review | Oncology (Williston Park) | Novel therapies for metastatic triple-negative breast cancer |
| 40192953 | 2025 | Retrospective cohort | Mol Diagn Ther | Actionability of molecular targets in multi-ethnic breast cancer patients |
| 40471518 | 2025 | Phase I/II trial | Breast Cancer Res Treat | Gedatolisib plus talazoparib in advanced triple-negative or BRCA-mutated, HER2-negative breast cancer |
| 39516069 | 2025 | Real-world cohort | Clin Breast Cancer | Prescribing patterns and outcomes of PARP inhibitors in metastatic breast cancer (Mayo Clinic) |
Singapore Market Information
| Authorization Number | Product Name | Dosage Form | Approved Indication |
|---|---|---|---|
| SIN15945P | TALZENNA CAPSULE 1MG | Capsule | Not stated in the record |
| SIN15944P | TALZENNA CAPSULE 0.25MG | Capsule | Not stated in the record |
Both licences are valid single-ingredient products from Excella GmbH & Co. KG, for oral use.
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Targeted therapy (PARP inhibitor) with DNA-damaging activity |
| Myelosuppression Risk | Medium to high (thrombocytopenia and other cytopenias are a recognised concern with this class) |
| Emetogenicity Classification | Low to medium |
| Monitoring Items | CBC with differential, liver and renal function |
| Handling Protection | Please refer to the package insert warnings and precautions; follow institutional procedures for handling antineoplastic drugs |
Safety Considerations
- Drug Interactions: The interaction screen returned 100 potential interactions. Major-level examples include clarithromycin, deferiprone and samarium (153Sm) lexidronam. Moderate-level examples include simvastatin, ticagrelor, cobicistat, eltrombopag, fostamatinib, erythromycin, chloramphenicol and roflumilast. Several of these involve additive myelosuppression or transporter/enzyme effects, so co-medication needs a pharmacist review.
Please refer to the package insert for warnings and contraindications.
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Talazoparib is already marketed in Singapore, and its activity in BRCA-mutated breast cancer is supported by Phase 2/3-level evidence. No trial or publication is specific to HER2-positive disease, so the evidence supports a biomarker-selected question (BRCA/HRD-positive patients) rather than an unrestricted new indication. Note that the "L2" grade reflects trials in the wider breast cancer setting, and the Phase 2 trials listed are not HER2-positive-specific.
To proceed, the following is needed:
- The Singapore package insert, to confirm approved indications, warnings and contraindications
- Mechanism-of-action data from DrugBank
- A defined biomarker-selected population (germline or somatic BRCA1/2 or HRD-positive HER2-positive patients)
- Subgroup data for HER2-positive patients from talazoparib-containing trials, including the I-SPY2 platform
- A myelosuppression monitoring plan and a medication review for the major interactions
Other predicted indications (for context):
- Progesterone-receptor negative breast cancer (score 98.34%, L2): the most plausible alternative, since it overlaps with triple-negative disease. A neoadjuvant Phase 2 study (PMID 31461380) reported pathologic responses in germline BRCA-mutated patients. Suggested decision: Research Question.
- Progesterone-receptor positive breast cancer (L3): evidence is limited to subgroup and observational data in BRCA-variant patients.
- Luminal A or B breast tumour, normal breast-like subtype, HIV infection, multiple endocrine neoplasia, primary release disorder of platelets, and the feline and simian immunodeficiency indications: Hold. These rest on model prediction or preclinical data only, with no supporting clinical trials.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.