Olaparib

證據等級: L5

預測適應症: 10 個

Olaparib: From Ovarian Cancer to Female Breast Carcinoma

One-Sentence Summary

Olaparib is a PARP1/2 inhibitor whose first approved oncology indication was BRCA-mutated ovarian cancer. The TxGNN model predicts it may also be effective for Female Breast Carcinoma, and this is not a purely exploratory hypothesis — 50 clinical trials and 20 publications were identified for this drug–disease pair, including the pivotal OlympiA and OlympiAD randomised trials that already underpin international regulatory approvals in gBRCA-mutated breast cancer.

Quick Overview

Item	Content
Original Indication	Ovarian cancer (BRCA1/2-mutated) — internationally established indication; no Danish licence record is available in the current dataset
Predicted New Indication	Female Breast Carcinoma
TxGNN Prediction Score	99.09%
Evidence Level	L1
Denmark Market Status	Not marketed (未上市)
Number of Marketing Authorisations	0
Recommended Decision	Proceed with Guardrails

Why is This Prediction Reasonable?

Detailed structured mechanism-of-action data is not available in this evidence pack (Data Gap DG002). Based on the evidence collected alongside the prediction, olaparib is a poly(ADP-ribose) polymerase (PARP) 1/2 inhibitor. It blocks single-strand DNA repair, which is selectively lethal (“synthetic lethality”) to tumour cells that already carry a homologous recombination deficiency (HRD) — most notably germline or somatic BRCA1/2 mutations.

Ovarian cancer and breast cancer share this same molecular vulnerability: approximately 5–10% of breast cancers, and a much larger share of high-grade serous ovarian cancers, carry a deleterious BRCA1/2 variant. Because olaparib’s original approval was built on exploiting BRCA-driven HRD in ovarian cancer, extending it to BRCA-mutated breast cancer is a mechanistically direct, not speculative, extension.

Consistent with this, the connection TxGNN surfaced is not a novel hypothesis but a recovery of an already-validated, internationally approved indication: olaparib (Lynparza) received FDA approval for gBRCA-mutated, HER2-negative metastatic breast cancer in 2018 (OlympiAD) and was extended to the adjuvant early-breast-cancer setting in 2022 (OlympiA). This explains the very high prediction score and the L1 evidence level.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT06580314	Phase 3	Recruiting	880	One vs. two years of maintenance olaparib ± bevacizumab in BRCA1/2-mutated or HRD+ disease; graded “A” direct support for maintenance-duration optimisation.
NCT04330040	Phase 4	Completed	202	Post-marketing trial in Indian patients with platinum-sensitive relapsed ovarian cancer and gBRCA1/2-mutated metastatic breast cancer.
NCT01445418	Phase 1	Completed	103	Olaparib (AZD2281) + carboplatin dose-finding/expansion in BRCA1/2 carriers with breast and ovarian cancer, including sporadic TNBC.
NCT06201234	Phase 2	Recruiting	176	Elacestrant added to standard-of-care olaparib in HR+/HER2- locally advanced or metastatic breast cancer with gBRCA1/2 mutations.
NCT05498155	Phase 2	Active, not recruiting	50	Neoadjuvant olaparib monotherapy vs. olaparib + durvalumab in BRCA-mutated, early-stage HER2-negative breast cancer.
NCT05358639	Phase 1	Active, not recruiting	36	Olaparib + navitoclax (Bcl-2/Bcl-XL inhibitor) in BRCA1/2/PALB2-mutated triple-negative breast cancer and recurrent HGSC.
NCT03109080	Phase 1	Completed	24	Olaparib combined with radiation therapy in inflammatory, locoregionally advanced/metastatic or residual TNBC.
NCT04553926	N/A (post-marketing)	Completed	661	Regulatory post-marketing surveillance of Lynparza tablets in real-world South Korean practice, per approved indications.
NCT05258747	Phase 1	Completed	70	Bioequivalence study of generic vs. reference olaparib 150 mg tablets in BRCA-mutated ovarian/metastatic breast cancer patients.
NCT02734004	Phase 1/2	Active, not recruiting	264	Durvalumab + olaparib (± bevacizumab) in advanced solid tumours, including breast cancer, evaluating efficacy and safety.

Literature Evidence

PMID	Year	Type	Journal	Key Findings
34081848	2021	RCT	The New England Journal of Medicine	OlympiA: adjuvant olaparib significantly reduced recurrence in gBRCA1/2-mutated, high-risk HER2-negative early breast cancer.
28578601	2017	RCT	The New England Journal of Medicine	OlympiAD: olaparib improved progression-free survival vs. chemotherapy in gBRCA-mutated HER2-negative metastatic breast cancer.
36228963	2022	RCT	Annals of Oncology	OlympiA overall-survival analysis confirming durable benefit of adjuvant olaparib in gBRCA1/2 high-risk early breast cancer.
33119476	2020	RCT	Journal of Clinical Oncology	TBCRC 048: olaparib activity in metastatic breast cancer with somatic BRCA1/2 or non-BRCA homologous-recombination gene mutations.
36893711	2023	RCT	European Journal of Cancer	OlympiAD extended follow-up confirming safety and OS trend for olaparib vs. chemotherapy in gBRCA-mutated metastatic breast cancer.
30689707	2019	RCT	Annals of Oncology	OlympiAD final overall-survival and tolerability results for olaparib vs. physician’s-choice chemotherapy.
38588696	2024	RCT	Nature	PARTNER trial: neoadjuvant olaparib added to carboplatin-paclitaxel in BRCA-wild-type triple-negative breast cancer.
33710534	2021	Review	Targeted Oncology	Overview of PARP inhibitors (olaparib, talazoparib) approved for deleterious/suspected-deleterious germline BRCA-mutated breast cancer.
31650727	2020	Review	Annals of Laboratory Medicine	Review of BRCA1/BRCA2 pathogenic-variant breast cancer treatment and prevention strategies, including PARP-inhibitor rationale.
39791278	2025	Review	CA: A Cancer Journal for Clinicians	Pan-tumor review of PARP inhibitors (olaparib, talazoparib, rucaparib, niraparib) and synthetic-lethality mechanism across cancer types.

Denmark Market Information

No marketing authorisations for Olaparib are currently on record in Denmark — Laegemiddelstyrelsen data shows 0 licences and a market status of Not marketed. This is separate from the missing-label issue below (DG001): it reflects an actual absence of a registered product, not a data-collection gap.

Cytotoxicity

Item	Content
Cytotoxicity Classification	Targeted therapy — PARP1/2 inhibitor exploiting synthetic lethality in BRCA1/2-mutated or HRD tumours (not a conventional cytotoxic agent)
Myelosuppression Risk	Please refer to the Summary of Product Characteristics (SmPC) — no structured toxicity data available in this dataset
Emetogenicity Classification	Please refer to the Summary of Product Characteristics (SmPC) — no structured toxicity data available in this dataset
Monitoring Items	Please refer to the Summary of Product Characteristics (SmPC) — no structured toxicity data available in this dataset
Handling Protection	Please refer to the Summary of Product Characteristics (SmPC) — no structured toxicity data available in this dataset

Safety Considerations

Please refer to the approved Summary of Product Characteristics (SmPC) for safety information. No structured warnings, contraindications, or drug–drug interaction data were retrievable for this candidate (DDI query status: not found).

Conclusion and Next Steps

Decision: Proceed with Guardrails

Rationale: The mechanistic and clinical evidence base is strong (L1 — multiple completed Phase 3 RCTs, including OlympiA and OlympiAD, already support olaparib in BRCA-mutated breast cancer internationally). However, Denmark-specific regulatory documentation is missing, which blocks a full safety evaluation.

To proceed, the following is needed:

Danish/TFDA-equivalent product label (SmPC) — warnings and contraindications (Blocking gap, DG001; source: Laegemiddelstyrelsen label PDF)
Confirmed DrugBank mechanism-of-action record (High-priority gap, DG002)
Clarification of Danish marketing-authorisation pathway, given 0 current licences despite broad international approval
Drug–drug interaction data collection (current query status: not found)
Disclaimer

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