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
- Lee, CK; Scott, C; Lindeman, GJ; Hamilton, A; Lieschke, E; Gibbs, E; Asher, R; Badger, H; Paterson, R; Macnab, L; Kwan, EM; Francis, PA; Boyle, F; Friedlander, M;
Publication Year 2019-01-17, Volume 120, Issue #3, Page 279-285
- Journal Title
- British Journal of Cancer
- Publication Type
- Journal Article
- 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 [gBRCAm] 70%) and 9 had BC (gBRCAm 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 gBRCAm subset, respectively. CA125 responses were 70% (all HGSOC) and 92% (gBRCAm). CONCLUSIONS: In HGSOC and BC, olaparib 300 mg bid and cyclophosphamide 50 mg on days 1-5 weekly were tolerable and active, particularly in gBRCAm, and is worthy of further investigation.
- WEHI Research Division(s)
- Cancer Biology And Stem Cells; Clinical Translation
- PubMed ID
- Publisher's Version
- Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2019-03-13 08:04:16Last Modified: 2019-03-13 09:03:00