Phase 1 trial of olaparib and oral cyclophosphamide in BRCA breast cancer, recurrent BRCA ovarian cancer, non- BRCA triple-negative breast cancer, and non-BRCA ovarian cancer
BRITISH JOURNAL OF CANCER(2019)
摘要
Background We conducted a Phase 1 study to evaluate safety and activity of olaparib tablets and oral cyclophosphamide. Methods Patients had metastatic breast cancer (BC) or recurrent high-grade serous ovarian cancer (HGSOC), performance status 0–2, and ≤3 lines of prior therapy. Patients were treated using a dose escalation strategy with cohort expansion once maximal tolerated dose (MTD) was determined. Dose level 1 (DL1): olaparib 300 mg bid, cyclophosphamide 50 mg on days 1, 3, and 5, weekly. DL2: olaparib 300 mg bid, cyclophosphamide 50 mg, days 1–5 weekly. Results Of 32 patients, 23 had HGSOC (germline BRCA mutation [g BRCA m] 70%) and 9 had BC (g BRCA m 67%). Four were treated at DL1 and 28 at DL2, the MTD. Haematological adverse events (AEs) were most common: grade 3/4 AEs: lymphopenia 75%, anaemia 31%, neutropenia 37%, thrombocytopenia 47%. Two permanently discontinued treatment due to haematological AEs. In BC, no objective response was reported. Unconfirmed objective response was 48% and 64% for all HGSOC and g BRCA m subset, respectively. CA125 responses were 70% (all HGSOC) and 92% (g BRCA m). Conclusions In HGSOC and BC, olaparib 300 mg bid and cyclophosphamide 50 mg on days 1–5 weekly were tolerable and active, particularly in g BRCA m, and is worthy of further investigation.
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关键词
Cancer,Oncology,Biomedicine,general,Cancer Research,Epidemiology,Molecular Medicine,Drug Resistance
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