| Authors | Study Design | Methods of Data Collection and Analysis | Objective ResponseResults in BRCAm cohorts | Olaparib Dose | No. of Patients(No. with BRCAm BC) | Comments |
|---|---|---|---|---|---|---|
| Fong, 2009 | Phase 1 non randomised open label dose finding trial using 3+3 design.Single armmonotherapy | ORR, CR, PR measured using RECIST and CT or MRI scan. AEs measured using CTCAE | 33% at 400mg BiD | 10-600 BID | 60 (3) | Very small cohort. No written consent found. First in human trial. MTD found at 400 BiD |
| Tutt, 2010 | Phase 2 non randomised proof of concept open labelmonotherapy | ORR,CR, PR measured using RECIST and CT or MRI scan, AEs measured using CTCAE | 41% at 400mg BiD22% at 100 BiD | 400 or 100 BID | 54 (54) | Comparator arm on lower dose (100mg) = MTD is most effective. |
| Gelmon, 2011 | Phase 2 non randomisedOpen labelFour cancers studied. monotherapy | ORR,CR, PR measured using RECIST and CT or MRI scan, AEs measured using CTCAE | 0% | 400 BID | 90 (10) | Compares results between BRCAm or BRCAwt. Very small cohort. Heavily treated - 70% > 3 prior chemotherapy,TNBC = large heterogeneity among patients.3 patients data not confirmed. |
| Balmana, 2014 | Phase 1 non randomised dose finding trial, 3+ 3 design.Open-labelCombination therapy (with cisplatin) | ORR,CR, PR measured using RECIST and CT or MRI scan, AEs measured using CTCAE | 71%SD (>1 year) occurred in 5 breast cancer patients | 50-200 BID (continuous and intermittent dosing schedules) | 53 (17) | Patients BRCA status not centrally validatedSmall cohort. cisplatin 60 mg/m2 with intermittent olaparib 50 mg BID deemed tolerable but MTD not reached |
| Van der Noll, 2015 | Open-label Monotherapy long-term safety study following a Phase 1 single arm combination study (olaparib with carboplatin and/or paclitaxel). | AEs measured using CTCAE | N/A | 400BiD | 21 (5) | No written consent found. AEs reduced over time suggesting carryover from prior chemotherapy study. Mistake found in results text. Patients on therapy for up to 3.5 years. |
| Kaufman, 2015 | Phase 2 non randomisedOpen-label single armmonotherapy | ORR,CR, PR measured using RECIST and CT or MRI scan, AEs measured using CTCAE | 12.9% | 400 BID | 317 (62) | Very heavily pre-treated (average 4.6 prior therapies). No written consent found. 47% SD is a very good response rate given the heavy pre-treatment of these patients. |
| Robson, 2017 | Phase 3 randomisedOpen labelmonotherapy | ORR,CR, PR measured using RECIST and CT or MRI scan, AEs measured using CTCAE | 59.9% | 300 BID (tablet form) | 302 (302) | Not truly randomised as physicians choice was limited - and no placebo arm. Least pre-treated cohort with some patients only one prior treatment. Also measured QoL and PFS2. End point PFS was reached. |