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 an oral PARP1/2 inhibitor originally developed for BRCA-mutated, platinum-sensitive ovarian cancer maintenance therapy. 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 completed Phase 3 randomised controlled trials (OlympiA, OlympiAD).

Quick Overview

Item	Content
Original Indication	Ovarian cancer (BRCA-mutated, platinum-sensitive) — per trial-context literature in this pack; not independently confirmed via an Australian regulatory source
Predicted New Indication	Female Breast Carcinoma
TxGNN Prediction Score	99.09%
Evidence Level	L1
Australia Market Status	Not marketed
Number of ARTG Entries	0
Recommended Decision	Proceed with Guardrails

Why is This Prediction Reasonable?

Olaparib is a PARP1/2 inhibitor. In tumour cells with homologous recombination repair (HRR) deficiency — most notably germline or somatic BRCA1/2 mutations — PARP inhibition causes synthetic lethality: the cell loses its remaining DNA-repair backup pathway and dies. This mechanism is well established and is not a mechanistic hypothesis unique to this prediction; it is the basis of olaparib’s existing oncology use.

Breast and ovarian cancer share the same underlying genetic vulnerability. Approximately 5–10% of breast cancers carry a germline BRCA1/2 pathogenic variant, and these tumours are mechanistically comparable to BRCA-mutated ovarian cancer, olaparib’s original target population. This is why the TxGNN prediction is not purely computational extrapolation — it recapitulates a mechanism-disease relationship that has already been validated in large randomised trials (OlympiA for adjuvant early breast cancer, OlympiAD for metastatic breast cancer), both included in the evidence below.

Because the shared molecular driver (HRR/BRCA deficiency) rather than tissue-of-origin determines olaparib’s activity, the extension from ovarian to breast cancer is biologically coherent rather than speculative.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrolment	Key Findings
NCT04417192	Phase 2	Completed	30	Preoperative olaparib monotherapy vs olaparib + pembrolizumab in HRD-positive advanced epithelial ovarian/fallopian tube/peritoneal cancer (note: trial population is ovarian, not breast, despite being flagged under this indication)
NCT06201234	Phase 2	Recruiting	176	Addition of elacestrant to olaparib in HR-positive, HER2-negative, gBRCA1/2-mutated advanced breast cancer
NCT05498155	Phase 2	Active, not recruiting	50	Neoadjuvant olaparib ± durvalumab in BRCA-mutated, early-stage HER2-negative breast cancer
NCT03109080	Phase 1	Completed	24	Olaparib with radiation therapy in inflammatory/locoregionally advanced/metastatic or residual triple-negative breast cancer
NCT02418624	Phase 1	Completed	25	Carboplatin-olaparib followed by olaparib monotherapy vs capecitabine as first-line treatment in BRCA1/2-mutated HER2-negative advanced breast cancer
NCT01445418	Phase 1	Completed	103	Olaparib (AZD2281) + carboplatin dose-finding in BRCA1/2-mutated and sporadic triple-negative breast and ovarian cancer
NCT05358639	Phase 1	Active, not recruiting	36	Olaparib + navitoclax in BRCA1/2/PALB2-mutated triple-negative breast cancer and recurrent high-grade serous ovarian cancer
NCT04330040	Phase 4	Completed	202	Real-world Indian cohort: olaparib in platinum-sensitive relapsed ovarian cancer and metastatic breast cancer with germline BRCA1/2 mutation
NCT04024254	Phase 4	Completed	10	Serum folate deficiency monitoring in patients on olaparib for advanced ovarian or breast cancer
NCT05209529	Phase 2	Withdrawn	0	Neoadjuvant olaparib ± durvalumab in BRCA-associated triple-negative breast cancer (trial withdrawn — enrolment never began)

50 trials in total were identified for this indication; the above are the 10 most directly relevant to breast cancer.

Literature Evidence

PMID	Year	Type	Journal	Key Findings
34081848	2021	RCT (Phase 3, OlympiA)	New England Journal of Medicine	Adjuvant olaparib reduced invasive disease recurrence in BRCA1/2-mutated, HER2-negative high-risk early breast cancer
36228963	2022	RCT (OlympiA, overall survival)	Annals of Oncology	Overall survival analysis of the OlympiA trial confirming sustained benefit of adjuvant olaparib in gBRCA1/2 early breast cancer
28578601	2017	RCT (Phase 3, OlympiAD)	New England Journal of Medicine	Olaparib improved outcomes vs chemotherapy in metastatic breast cancer with a germline BRCA mutation
30689707	2019	RCT (OlympiAD, final OS)	Annals of Oncology	Final overall survival and tolerability results for olaparib vs physician’s choice chemotherapy in gBRCAm, HER2-negative metastatic breast cancer
36893711	2023	RCT (OlympiAD, extended follow-up)	European Journal of Cancer	Extended follow-up safety and survival data for olaparib in gBRCAm HER2-negative metastatic breast cancer
33119476	2020	RCT (Phase 2, TBCRC 048)	Journal of Clinical Oncology	Olaparib activity in metastatic breast cancer with somatic BRCA or other homologous-recombination gene mutations (beyond germline BRCA1/2)
34143979	2021	RCT (Phase 2, I-SPY2)	Cancer Cell	Durvalumab + olaparib + paclitaxel increased pathologic complete response in high-risk HER2-negative breast cancer
38588696	2024	RCT (Phase 2/3, PARTNER)	Nature	Neoadjuvant olaparib added to carboplatin-paclitaxel in germline 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, HER2-negative breast cancer
31650727	2020	Review	Annals of Laboratory Medicine	BRCA1/2 pathogenic variant breast cancer: treatment and prevention strategies, including PARP inhibitor use

20 publications in total were identified; the above 10 are prioritised by RCT strength.

Australia Market Information

Olaparib currently has no ARTG entries in this evidence pack’s regulatory data — it is recorded as not marketed in Australia. No approved indication text, product name, or dosage form information is available to tabulate.

Cytotoxicity

Item	Content
Cytotoxicity Classification	Targeted therapy (PARP inhibitor) — not a conventional cytotoxic agent
Myelosuppression Risk	Medium — anaemia, neutropenia and thrombocytopenia are recognised class effects of PARP inhibitors, referenced in trial literature in this pack (e.g. NCT06572735 notes PARP inhibitor toxicity to haematopoietic tissue); please refer to the PI for full detail
Emetogenicity Classification	Please refer to the Product Information (PI) warnings and precautions
Monitoring Items	Full blood count (FBC) is advisable given the class-wide haematological toxicity signal; please refer to the PI for the complete monitoring schedule
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.

Conclusion and Next Steps

Decision: Proceed with Guardrails

Rationale: Two completed Phase 3 RCTs (OlympiA, OlympiAD) and multiple supporting Phase 1/2 studies establish strong mechanistic and clinical evidence for olaparib in BRCA-mutated breast cancer (L1 evidence). However, olaparib is not currently registered in Australia, and key drug-level data (MOA documentation, TFDA/TGA warnings, contraindications, and DDI) remain unresolved gaps that block a complete safety assessment.

To proceed, the following is needed:

TGA-approved Product Information (warnings, contraindications) — currently a blocking data gap
Confirmed mechanism of action documentation via DrugBank
Assessment of the regulatory pathway for ARTG registration, since olaparib is not currently marketed in Australia
Completion of drug-drug interaction (DDI) data
Disclaimer

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