Olaparib

證據等級: L5

預測適應症: 1 個

Olaparib: From BRCA-Mutated Ovarian Cancer to Breast Carcinoma

One-Sentence Summary

Olaparib is a PARP1/2 inhibitor originally developed and approved internationally for BRCA-mutated ovarian cancer maintenance therapy. The TxGNN model flags Female Breast Carcinoma as a related indication, with 73 clinical trials and 20 publications in the evidence pack — however, this is very likely an already-established indication (olaparib has been approved for gBRCA-mutated HER2-negative breast cancer since 2018) rather than a genuinely novel repurposing signal. See caveat below.

⚠️ Data quality note: drug.original_indications and taiwan_regulatory.licenses are both empty in this Evidence Pack, and original_moa is flagged as a data gap (DG002). The repurposing rationale itself flags this as a likely database omission, since olaparib (Lynparza®) is a well-established, globally approved oncology drug. This report is written strictly from the supplied Evidence Pack; external verification against the actual TFDA/Norway label is required before any decision.

Quick Overview

Item	Content
Original Indication	Not available in Evidence Pack (0 licenses recorded); publicly known original approval: BRCA-mutated, platinum-sensitive relapsed ovarian cancer (maintenance therapy)
Predicted New Indication	Female Breast Carcinoma
TxGNN Prediction Score	99.09%
Evidence Level	L1
Norway Market Status	✗ Not Marketed (未上市)
Number of Authorizations	0
Recommended Decision	Proceed with Guardrails

Why is This Prediction Reasonable?

Currently, no structured MOA field is available for olaparib in this Evidence Pack (DG002, High severity). However, the repurposing rationale supplies the mechanistic basis: olaparib is a PARP1/2 (poly-ADP-ribose polymerase) inhibitor. In tumor cells with BRCA1/2 mutations or broader homologous recombination deficiency (HRD), PARP inhibition blocks single-strand DNA damage repair, causing accumulation of double-strand breaks and cell death via synthetic lethality. This mechanism has been extensively validated both biologically and clinically in BRCA-mutated tumors.

BRCA1/2 mutations drive both hereditary ovarian cancer and hereditary breast cancer through the same DNA-repair pathway. Since olaparib's synthetic-lethality mechanism is gene-defect–driven rather than tissue-specific, its efficacy readily extends from ovarian to breast cancer in patients sharing the same germline BRCA1/2 mutation — this is not a speculative repurposing hypothesis but a mechanistically expected and clinically confirmed extension.

Importantly, the clinical evidence in this pack (OlympiAD, OlympiA) shows this "predicted" indication is already an approved, guideline-standard use of olaparib in gBRCA-mutated HER2-negative breast cancer (both metastatic and high-risk early-stage adjuvant settings) in multiple jurisdictions since 2018–2022. The TxGNN signal here should be interpreted as evidence confirmation of an existing indication, not discovery of a novel one.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT02282020	Phase 3	Completed	266	Olaparib monotherapy vs. physician's choice single-agent chemotherapy in platinum-sensitive relapsed, gBRCA1/2-mutated ovarian cancer
NCT03162627	Phase 1	Active, not recruiting	90	Selumetinib + olaparib in solid tumors (incl. breast) with Ras pathway alterations or PARP resistance
NCT02418624	Phase 1	Completed	25	Carboplatin + olaparib → olaparib monotherapy vs. capecitabine as first-line therapy in BRCA1/2-mutated HER2-negative advanced breast cancer
NCT03402841	Phase 3b	Completed	279	Single-arm olaparib maintenance in platinum-sensitive relapsed non-germline BRCA ovarian/endometrioid cancer
NCT02503436	N/A (observational)	Completed	276	C-PATROL: real-world effectiveness/safety of olaparib in BRCAm+ platinum-sensitive relapsed ovarian cancer
NCT00679783	Phase 2	Completed	99	AZD2281 (olaparib) in BRCA-mutated/triple-negative breast cancer and recurrent ovarian cancer — response rate and correlative biomarkers
NCT05564377	Phase 2	Recruiting	2900	ComboMATCH biomarker-directed combination therapy platform trial, includes breast cancer cohorts
NCT04421963	Phase 3	Active, not recruiting	185	ROSY-O rollover study providing continued olaparib treatment post parent-study completion
NCT06545942	Phase 1	Active, not recruiting	220	MOMA-313 monotherapy or combined with a PARP inhibitor (olaparib) in advanced/metastatic solid tumors
NCT04330040	Phase 4	Completed	202	Olaparib in Indian patients with platinum-sensitive relapsed ovarian cancer and BRCA1/2-mutated metastatic breast cancer

Note: 43 additional trials in the evidence pack are graded "pending" (unreviewed relevance) and are omitted from this table; most are combination/basket trials across multiple solid tumor types rather than breast-cancer-specific.

Literature Evidence

PMID	Year	Type	Journal	Key Findings
28578601	2017	RCT	N Engl J Med	OlympiAD: olaparib shows antitumor activity in metastatic breast cancer with germline BRCA mutation
34081848	2021	RCT	N Engl J Med	OlympiA: adjuvant olaparib reduces recurrence in gBRCA1/2-mutated, HER2-negative early breast cancer
30689707	2019	RCT	Ann Oncol	OlympiAD final OS and tolerability: olaparib vs. chemotherapy in gBRCA-mutated HER2-negative mBC
36228963	2022	RCT	Ann Oncol	OlympiA phase 3 overall survival results for adjuvant olaparib in high-risk early breast cancer
36893711	2023	RCT	Eur J Cancer	OlympiAD extended follow-up: sustained OS and safety data for olaparib in gBRCAm HER2-negative mBC
33119476	2020	Phase 2 single-arm	J Clin Oncol	TBCRC 048: olaparib activity in mBC with somatic BRCA1/2 or non-BRCA HR-related gene mutations
34143979	2021	Phase 2 combination	Cancer Cell	I-SPY2: durvalumab + olaparib + paclitaxel increases pCR in high-risk HER2-negative breast cancer
33710534	2021	Review	Target Oncol	Overview of PARP inhibitors (olaparib, talazoparib) approved for BRCA-mutated HER2-negative breast cancer
35163586	2022	Review	Int J Mol Sci	Molecular mechanisms, biomarkers and emerging therapies for chemotherapy-resistant TNBC
37253112	2023	Translational/Functional	Cancer Res	Functional characterization of RAD51C variants relevant to HR-deficiency and PARP inhibitor sensitivity

Norway Market Information

No authorization records are present in the Evidence Pack (total_licenses: 0, licenses: []). Olaparib currently has no registered marketing authorization in Norway per this data source. This should be independently verified against the national medicines register before proceeding, since olaparib (Lynparza®) is centrally authorized in the EU/EEA and would ordinarily be expected to appear.

Cytotoxicity

Olaparib is an antineoplastic agent (PARP inhibitor, oncology indication) and this section therefore applies.

Item	Content
Cytotoxicity Classification	Targeted therapy (PARP inhibitor; synthetic lethality in HR-deficient tumors)
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 warnings and precautions
Handling Protection	Please refer to the package insert warnings and precautions

Detailed toxicity/monitoring data could not be sourced — this is blocked by DG001 (TFDA label warnings/contraindications not yet retrieved).

Safety Considerations

Please refer to the package insert for safety information. No key warnings, contraindications, or drug-drug interaction data are currently available in this Evidence Pack (all fields flagged as data gaps; DDI query returned no results).

Conclusion and Next Steps

Decision: Proceed with Guardrails

Rationale: Clinical evidence is strong (5 Phase 3 RCTs, including two pivotal trials — OlympiAD and OlympiA — directly establishing olaparib's efficacy in gBRCA-mutated breast cancer), justifying Evidence Level L1. However, this appears to represent confirmation of an already internationally approved indication rather than a novel repurposing candidate, and critical safety and regulatory data (TFDA/Norway label, MOA, market authorization) are missing from this pack — hence guardrails rather than an unconditional Go.

To proceed, the following is needed:

Resolve DG001 (Blocking): retrieve and parse the actual product label for warnings, contraindications, and DDI data
Resolve DG002 (High): confirm structured MOA from DrugBank API
Verify actual Norway/EEA marketing authorization status for olaparib (Lynparza®), since 0 licenses in this pack is inconsistent with its known EU centralized authorization
Confirm whether "female breast carcinoma" should be reclassified as an existing approved indication rather than a TxGNN-predicted new indication, to avoid mischaracterizing this candidate in downstream reporting
Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.