Pertuzumab
| 證據等級: L5 | 預測適應症: 10 個 |
目錄
- Pertuzumab
- Pertuzumab: From HER2-Positive Breast Cancer to Progesterone-Receptor Positive Breast Cancer
Pertuzumab: From HER2-Positive Breast Cancer to Progesterone-Receptor Positive Breast Cancer
One-Sentence Summary
Pertuzumab (DrugBank DB06366) is an anti-HER2 monoclonal antibody whose established use is in HER2-positive breast cancer. The TxGNN model’s top-ranked prediction — progesterone-receptor positive breast cancer — is best understood as a receptor-status refinement within pertuzumab’s existing HER2-positive breast cancer population rather than a genuinely new disease target, with 10 clinical trials (including 2 completed Phase 3 RCTs) and 20 publications currently supporting the mechanistic link.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | HER2-positive breast cancer (inferred from repurposing rationale text; not separately confirmed via ARTG licence data — see note below) |
| Predicted New Indication | Progesterone-Receptor Positive Breast Cancer |
| TxGNN Prediction Score | 99.93% |
| Evidence Level | L1 |
| Australia Market Status | Not Marketed (0 ARTG entries recorded in this evidence pack) |
| Number of ARTG Entries | 0 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
Detailed structured mechanism-of-action data was not returned by the DrugBank query for this evidence pack. However, the underlying repurposing analysis for this candidate explicitly documents pertuzumab’s mechanism: it is a HER2-targeted monoclonal antibody that blocks heterodimerisation of HER2 with HER1/HER3/HER4, interrupting downstream HER2 signalling. This mechanism is already well established as the basis for pertuzumab’s approved use in HER2-positive breast cancer.
Progesterone-receptor (PR) status is a hormone-receptor stratification variable measured alongside HER2 status in breast cancer, not a distinct disease entity. A tumour that is “PR-positive breast cancer” and HER2-positive sits squarely within the population pertuzumab already targets — the predicted indication therefore represents an extension/refinement of an existing approved-use population rather than a mechanistically novel repurposing candidate. This explains both the very high TxGNN score and the unusually strong evidence base (multiple completed Phase 3 trials) for what is nominally a “new” indication.
Because of this overlap, the clinical trial and literature evidence below should be read as supporting pertuzumab’s activity in HER2-positive/PR-positive disease specifically (as a biomarker-defined subgroup), rather than as evidence for a mechanistically unrelated new use.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrolment | Key Findings |
|---|---|---|---|---|
| NCT04629846 | Phase 3 | Completed | 517 | Randomised, double-blind biosimilar (QL1209) vs pertuzumab, both with trastuzumab + docetaxel, in HER2-positive/ER/PR-negative early-stage breast cancer. |
| NCT03726879 | Phase 3 | Completed | 454 | IMpassion050 — atezolizumab vs placebo added to neoadjuvant anthracycline/taxane + trastuzumab + pertuzumab in early HER2-positive breast cancer. |
| NCT00545688 | Phase 2 | Completed | 417 | 4-arm neoadjuvant comparison of Herceptin ± docetaxel ± pertuzumab in locally advanced/inflammatory/early HER2-positive breast cancer; pathological complete response endpoint. |
| NCT05802225 | Phase 3 | Active, not recruiting | 398 | Biosimilar (BCD-178) vs Perjeta as neoadjuvant therapy for HER2-positive breast cancer without ER/PR expression. |
| NCT02326974 | Phase 2 | Active, not recruiting | 164 | T-DM1 + pertuzumab preoperative therapy, studying impact of HER2 heterogeneity on treatment response. |
| NCT00999804 | Phase 2 | Active, not recruiting | 128 | TBCRC 023 — neoadjuvant lapatinib + trastuzumab with/without endocrine therapy, 12 vs 24 weeks, in HER2-overexpressing breast cancer. |
| NCT04675827 | Phase 2 | Terminated | 139 | DECRESCENDO — de-escalated neoadjuvant chemotherapy plus SC pertuzumab/trastuzumab in HER2-positive, ER-negative, node-negative early breast cancer. |
| NCT06131424 | N/A | Completed | 1151 | Retrospective multicentre study of HER2-low prevalence and treatment patterns in HER2-negative metastatic breast cancer (indirect relevance). |
| NCT02689921 | Phase 2 | Unknown | 7 | NEOADAPT — chemotherapy-free neoadjuvant aromatase inhibitor + pertuzumab/trastuzumab in HR-positive (incl. PR+), HER2-positive early breast cancer. |
| NCT03058939 | Phase 2 | Withdrawn | 0 | Single-arm neoadjuvant paclitaxel response-rate study in Nigerian women with breast cancer (pertuzumab not central). |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 37166817 | 2023 | RCT | JAMA Oncology | WSG-TP-II — endocrine therapy + trastuzumab/pertuzumab vs de-escalated chemotherapy in HR-positive/HER2-positive early breast cancer. |
| 37609714 | 2023 | RCT | Future Oncology | DECRESCENDO — de-escalating chemotherapy in HER2-positive, hormone receptor-negative, node-negative early breast cancer. |
| 30106636 | 2018 | RCT (Phase 2) | J Clin Oncol | PERTAIN — trastuzumab + aromatase inhibitor ± pertuzumab in HER2-positive and hormone receptor-positive metastatic/locally advanced breast cancer. |
| 37723497 | 2023 | Cohort | World J Surg Oncol | Real-world retrospective study (China) finding PR status a more decisive factor than ER status for pertuzumab benefit in HER2-positive, node-positive breast cancer. |
| 35640077 | 2022 | Review | J Clin Oncol | ASCO guideline update on systemic therapy for advanced HER2-positive breast cancer. |
| 27179402 | 2016 | Cohort | Lancet Oncology | NeoSphere 5-year follow-up — neoadjuvant pertuzumab + trastuzumab in HER2-positive breast cancer. |
| 38906970 | 2024 | Phase 3 equivalence trial | British J Cancer | QL1209 (pertuzumab biosimilar) vs reference pertuzumab, both + trastuzumab + docetaxel, in HER2-positive, ER/PR-negative breast cancer. |
| 28945833 | 2017 | Phase 2 trial | Annals of Oncology | WSG-ADAPT HER2+/HR- — 12-week neoadjuvant dual HER2 blockade ± paclitaxel. |
| 40076535 | 2025 | Systematic Review | Int J Mol Sciences | Pertuzumab + trastuzumab + docetaxel as adjuvant doublet therapy for HER2-positive breast cancer. |
| 28973704 | 2017 | Review | Southern Medical Journal | Overview of neoadjuvant and adjuvant therapies across breast cancer molecular subtypes, including HER2-enriched disease. |
Australia Market Information
This evidence pack records no ARTG entries and a market status of Not Marketed for pertuzumab. No product name, dosage form, or approved-indication text was retrievable from the regulatory data source used to build this pack. This should be treated as a data gap requiring verification rather than a confirmed regulatory finding, since pertuzumab-containing products are marketed in a number of jurisdictions internationally — the current TGA/ARTG registration status should be confirmed directly against the TGA product database before any decision is finalised.
Cytotoxicity
| Item | Content |
|---|---|
| Cytotoxicity Classification | Targeted therapy (anti-HER2 monoclonal antibody) |
| Myelosuppression Risk | Please refer to the Product Information (PI) warnings and precautions |
| Emetogenicity Classification | Please refer to the Product Information (PI) warnings and precautions |
| Monitoring Items | Please refer to the Product Information (PI) warnings and precautions |
| Handling Protection | Please refer to the Product Information (PI) warnings and precautions |
Safety Considerations
Please refer to the TGA-approved Product Information (PI) for safety information. No key warnings, contraindications, or drug-drug interaction data were returned for pertuzumab in this evidence pack (DDI query status: not found).
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale: Evidence level L1 is met on the strength of two completed Phase 3 RCTs (NCT04629846, NCT03726879) directly evaluating pertuzumab-based regimens in this receptor-defined population, supported by a further eight trials and ten relevant publications, including one real-world study specifically addressing PR status as a predictor of pertuzumab benefit (PMID 37723497). However, because PR-positive status sits within pertuzumab’s existing HER2-positive breast cancer population rather than representing a mechanistically distinct disease, this candidate should be framed as a biomarker-defined subgroup confirmation rather than novel repurposing.
To proceed, the following is needed:
- TGA-approved Product Information — warnings/precautions and contraindications (flagged as a Blocking data gap; required before any S1 safety assessment can proceed)
- Confirmed, structured mechanism-of-action data from DrugBank (High-priority gap; current MOA description was reconstructed from rationale text, not a primary source field)
- Verification of actual TGA/ARTG registration status for pertuzumab in Australia, given the “Not Marketed / 0 ARTG entries” result is inconsistent with pertuzumab’s known international marketing status and should be checked directly against the TGA database
- Confirmation of drug interaction data (currently returned as not found)
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.