Olaparib

證據等級: L5

預測適應症: 1 個

Olaparib: From Ovarian Cancer to Breast Cancer

One-Sentence Summary

Olaparib is an oral PARP1/2 inhibitor originally developed for BRCA-mutated, platinum-sensitive ovarian cancer. The TxGNN model predicts it may also be effective for female breast carcinoma, with 50 clinical trials and 20 publications currently supporting this direction, including two pivotal completed Phase 3 RCTs (OlympiAD, OlympiA).

Quick Overview

Item	Content
Original Indication	Ovarian cancer, BRCA-mutated (per international approval; not confirmed in Finnish labeling — see Data Gap below)
Predicted New Indication	Female Breast Carcinoma
TxGNN Prediction Score	99.09%
Evidence Level	L1
Finland Market Status	✗ Not Marketed
Number of Authorizations	0
Recommended Decision	Proceed with Guardrails

Why is This Prediction Reasonable?

Currently, detailed mechanism of action data from the drug label is not available (data gap). Based on the evidence pack's repurposing rationale, olaparib is a PARP1/2 (poly ADP-ribose polymerase) inhibitor that acts through synthetic lethality: in tumor cells with BRCA1/BRCA2 mutations or other homologous recombination deficiency (HRD), blocking PARP-mediated single-strand DNA repair leads to accumulation of unrepaired double-strand breaks and cell death.

Olaparib's original use was in BRCA-mutated, platinum-sensitive ovarian cancer, where this synthetic-lethality mechanism is well established. BRCA1/2 mutations drive both ovarian and breast cancer through the same defective homologous-recombination-repair biology, so the mechanistic link between the two indications is direct rather than speculative — it is not an analogy across unrelated tumor types but the same molecular vulnerability expressed in a different tissue.

This is reflected in the maturity of the evidence: olaparib is already internationally approved (FDA/EMA) for gBRCA-mutated, HER2-negative breast cancer (both adjuvant and metastatic settings), supported by two independent, completed Phase 3 RCTs — OlympiAD (metastatic setting) and OlympiA (adjuvant, early-stage, high-risk setting). This substantially strengthens confidence in the TxGNN prediction beyond a purely model-driven signal.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT02282020	Phase 3	Completed	266	OlympiAD: olaparib vs. physician's-choice chemotherapy in gBRCA-mutated, HER2-negative metastatic breast cancer — pivotal registration trial
NCT02418624	Phase 1/2	Completed	25	Carboplatin-olaparib sequential therapy vs. capecitabine as first-line treatment in BRCA1/2-mutated, HER2-negative advanced breast cancer
NCT03402841	Phase 3b	Completed	279	Single-arm maintenance olaparib in platinum-sensitive relapsed non-gBRCA ovarian cancer; supportive real-world efficacy/safety data
NCT02503436	N/A	Completed	276	C-PATROL: prospective non-interventional study collecting real-world effectiveness/safety data in BRCA-mutated ovarian cancer
NCT00679783	Phase 2	Completed	99	AZD2281 (olaparib) in BRCA-mutated/recurrent ovarian cancer and BRCA-mutated/triple-negative breast cancer; early proof-of-concept for later Phase 3 trials
NCT03162627	Phase 1	Active, not recruiting	90	Selumetinib + olaparib combination in Ras-altered/PARP-resistant solid tumors including breast cancer; early dose-finding, not breast-specific
NCT04421963	Phase 3	Active, not recruiting	185	ROSY-O rollover study providing continued olaparib access and long-term safety follow-up, not an efficacy endpoint trial
NCT06545942	Phase 1	Active, not recruiting	220	MOMA-313 alone or combined with a PARP inhibitor in HRD-positive advanced/metastatic solid tumors
NCT05564377	Phase 2	Recruiting	2900	ComboMATCH: genomically-directed basket trial platform; breast cancer is one of multiple sub-cohorts
NCT04330040	Phase 4	Completed	202	Phase IV trial in Indian patients with platinum-sensitive ovarian cancer and gBRCA1/2-mutated metastatic breast cancer

Literature Evidence

PMID	Year	Type	Journal	Key Findings
34081848	2021	RCT	N Engl J Med	OlympiA: adjuvant olaparib significantly improves invasive disease-free survival in gBRCA1/2-mutated, high-risk early breast cancer
36228963	2022	RCT	Ann Oncol	OlympiA overall survival follow-up confirming durable benefit of adjuvant olaparib in gBRCA1/2-mutated early breast cancer
28578601	2017	RCT	N Engl J Med	OlympiAD: olaparib shows antitumor activity in gBRCA-mutated metastatic breast cancer, establishing the pivotal efficacy signal
30689707	2019	RCT	Ann Oncol	OlympiAD final overall survival and tolerability results vs. chemotherapy in gBRCA-mutated HER2-negative metastatic breast cancer
36893711	2023	RCT	Eur J Cancer	OlympiAD extended follow-up: median OS 19.3 vs. 17.1 months for olaparib vs. chemotherapy, reaffirming safety profile
33119476	2020	RCT	J Clin Oncol	TBCRC 048 Phase 2: olaparib activity in metastatic breast cancer with somatic BRCA or other HR-related gene mutations beyond germline BRCA
34143979	2021	RCT	Cancer Cell	I-SPY2: durvalumab + olaparib + paclitaxel increases pathologic complete response in high-risk HER2-negative stage II/III breast cancer
39520738	2024	Phase 2 study	Breast (Edinburgh)	NOBROLA: olaparib monotherapy activity in advanced triple-negative breast cancer with HRD but no germline BRCA1/2 mutation
38112922	2024	Real-world study	Breast Cancer Res Treat	LUCY final analysis: real-world effectiveness and safety of olaparib in gBRCA-mutated, HER2-negative metastatic breast cancer
33710534	2021	Review	Targeted Oncology	Overview of PARP inhibitors (olaparib, talazoparib) approved as monotherapy for deleterious/suspected germline BRCA-mutated, HER2-negative breast cancer

Finland Market Information

Olaparib currently has no marketing authorization on record in Finland (0 authorizations; market status: not marketed).

Cytotoxicity

Item	Content
Cytotoxicity Classification	Targeted therapy (PARP inhibitor, synthetic lethality mechanism — not a conventional cytotoxic chemotherapeutic)
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

Safety Considerations

Please refer to the package insert for safety information.

Conclusion and Next Steps

Decision: Proceed with Guardrails

Rationale: The mechanistic and clinical evidence is strong — two independent, completed Phase 3 RCTs (OlympiAD, OlympiA) support olaparib's efficacy in BRCA-mutated breast cancer, meeting L1 evidence criteria. However, the drug is not currently marketed in Finland, and Blocking/High-severity data gaps (TFDA-equivalent label warnings/contraindications, detailed MOA) prevent a full safety review, so guardrails are required before advancing.

To proceed, the following is needed:

Finnish package insert (warnings, contraindications, DDI) to clear the Blocking data gap (DG001)
Confirmed original approved indication and detailed MOA from DrugBank (DG002)
Confirmation of Finland market authorization pathway, since the drug is currently unmarketed
DDI database query (current status: not_found) to complete the S1 safety pre-assessment
Disclaimer

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