Breast cancer is the most common malignancy in women; approximately 5-10% are hereditary, with 14% of triple-negative breast cancers (TNBC) harboring BRCA mutations. BRCA1/2 are essential for homologous recombination repair of DNA double-strand breaks, whereas PARP mediates base-excision repair of single-strand breaks. PARP inhibitors (PARPi) exploit synthetic lethality to selectively eliminate BRCA-deficient tumor cells. Olaparib and talazoparib have demonstrated superior PFS and ORR versus chemotherapy in BRCA-mutated, HER2-negative advanced breast cancer, leading to FDA approval. In ovarian cancer, PARPi maintenance improves overall survival, with consistent benefits observed in Asian populations. The domestically developed PARPi fluzoparib, engineered with a trifluoromethyl moiety for enhanced stability and tissue penetration, showed in the phase III FABULOUS trial a median PFS of 6.7 vs 3.0 months and an ORR of 43.6% vs 23.3% compared with chemotherapy in gBRCA-mutated, HER2-negative breast cancer, with manageable safety. Data remain limited in Chinese patients and those with BRCA wild-type disease. This study aims to evaluate the efficacy and safety of fluzoparib maintenance monotherapy in advanced TNBC patients-either BRCA1/2-mutated or wild-type-who have derived clinical benefit from prior platinum-based therapy.
Age 18-75 years (inclusive) at the time of informed consent.
Histologically confirmed triple-negative breast cancer (TNBC; ER <1%, PR <1%, HER2-negative).
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
Received ≥2 prior lines of systemic therapy, including a platinum-based regimen (single-agent or combination); must have achieved partial response (PR) or stable disease (SD) during or after that platinum-based treatment.
Known hypersensitivity to fluzoparib or any of its excipients.
Prior treatment with any PARP inhibitor.
Use of strong CYP3A4 inhibitors within 14 days or strong CYP3A4 inducers within 28 days before first dose.
Wash-out interval <4 weeks from any prior anti-cancer therapy (chemotherapy, radiotherapy, surgery, targeted therapy, immunotherapy) to first dose.
Single group
Fluzoparib Monotherapy
DrugFluzoparib is an oral poly (ADP-ribose) polymerase (PARP) inhibitor supplied as 50 mg capsules. Participants take 150 mg twice daily (total 300 mg/day) on days 1-28 of each 28-day cycle. Doses should be swallowed whole with water, approximately 12 hours apart, at approximately the same times each day. Treatment continues until disease progression, unacceptable toxicity, withdrawal of consent, or death. Dose interruptions or reductions (stepwise to 100 mg BID or 50 mg BID) are allowed for haematological or non-haematological toxicities graded ≥3 or as clinically indicated. No concurrent anticancer therapy is permitted during fluzoparib maintenance.
Progression-free survival (PFS)
Time from first fluzoparib dose to first radiological disease progression (RECIST 1.1) or death from any cause, whichever occurs first.
Second progression-free survival (PFS2)
Time from first dose of fluzoparib to the earliest of: radiological progression on next-line therapy, start of non-protocol anti-cancer treatment, or death from any cause.
Duration of response (DoR)
Time from first documented complete or partial response (CR/PR) to subsequent radiological disease progression (RECIST 1.1) or death from any cause, whichever occurs first, among patients who achieved CR/PR
Disease control rate (DCR)
Proportion of participants achieving complete response, partial response, or stable disease (CR + PR + SD) lasting ≥ 6 weeks, assessed by RECIST 1.1
Overall survival (OS)
Time from first dose of fluzoparib to death from any cause.
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