| General information |
| Database: | DB00516 |
| Objective: | They aimed to explore the hypothesis that olaparib is most likely to benefit patients with a BRCA mutation. |
| Authors: | Ledermann J, et al |
| Title: | Olaparib maintenance therapy in patients with platinumsensitive relapsed serous ovarian cancer: a preplanned retrospective analysis of outcomes by BRCA status in a randomisedphase 2 trial. |
| Journal: | Lancet Oncol. |
| Year: | 2014 |
| PMID: | 24882434 |
| Trial Design |
| Clinical Trial Id: | NCT00753545 |
| Agent: | olaparib
|
| Target: | Poly [ADPribose] polymerase1
|
| Cancer Type: | ovarian, primary peritoneal, or fallopian tube carcinoma |
| Cancer Subtype: | ovarian or fallopian tube cancer, or primary peritoneal cancer |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | phase II, randomised, doubleblind, multicentretrial |
| Key Patients Feature: | Eligible patients were aged 18 years or older and hadrecurrent ovarian or fallopian tube cancer, or primaryperitoneal cancer, with highgrade (grade 2 or 3) serousfeatures or a serous component, which was platinumsensitive (defined as no disease progression inthe first 6 months after the last dose of the penultimateline of platinumbased chemotherapy). Patients enteringthe study had received two or more previous courses ofplatinumbased chemotherapy and were required tohave shown an objective response (complete or partialresponse) according to Response Evaluation Criteria InSolid Tumors (RECIST) or Gynecologic CancerIntergroup criteria. Key inclusion criteria have beendescribed previously |
| Biomarker: | BRCA mutation status |
| Biomark Analysis: | Of patients with a BRCA mutation, median PFS was significantly longer in the olaparib group than in the placebo group (11.2 months [95% CI 8.3not calculable] vs 4.3 months [3.05.4]; HR 0.18 [0.100.31]; p<0.0001); similar findings were noted for patients with wildtype BRCA, although the difference between groups was lotheyr (7.4 months [5.510.3] vs 5.5 months [3.75.6]; HR 0.54 [0.340.85]; p=0.0075). At the second interim analysis of overall survival (58% maturity), overall survival did not significantly differ between the groups (HR 0.88 [95% CI 0.641.21]; p=0.44); similar findings were noted for patients with mutated BRCA (HR 0.73 [0.451.17]; p=0.19) and wildtype BRCA (HR 0.99 [0.631.55]; p=0.96). |
| Control Group Info: | 136 patients were assigned to olaparib and 129 to placebo |
| Treatment Info: | this study assessed maintenance treatment with olaparib 400 mg twice daily (capsules) versus placebo in patients with platinumsensitive recurrent serous ovarian cancer who had received two or more platinumbased regimens and who had a partial or complete response to their most recent platinumbased regimen. |
| Primary End Point: | PFS, analysed for the overall population and by BRCA status. |
| Secondary End Point: | NA |
| Patients Number: | 265 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | Patients with BRCA mutation treat with Olaparib (n=74), Complete response 49%, Partial response 51%, Patients with BRCA mutation treat with Placebo (n=62), Complete response 55%, Partial response 45%;Patients with wildtype BRCA treat with Olaparib (n=57), Complete response 35%, Partial response 65%, Patients with wildtype BRCA treat with Placebo (n=61), Complete response 41%, Partial response 59%, |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | Of patients with a BRCA mutation, median PFS was signifi cantly longer in the olaparib group than in the placebo group (11.2 months [95% CI 8.3-not calculable] vs 4.3 months [3.0-5.4]; HR 0.18 [0.10-0.31]; p<0.0001). patients with wildtype BRCA, (7.4 months [5.5-10.3] vs 5.5 months [3.7-5.6]; HR 0.54 [0.34-0.85]; p=0.0075) |
| Median OS A vs. C: | all patients: 29.8 (27.2-35.7) 27.8 (24.4-34.0). Patients with a BRCA mutation, olapanib vs placebo: 34.9 (29.2-NC) 31.9 (23.1-40.7). Patients without a BRCA mutation: 24.5 (19.8-35.0) 26.2 (22.6-33.7) months |
| Adverse Event(agent arm): | The most common grade 3 or worse adverse events in the olaparib group were fatigue (in ten [7%] patients in the olaparib group vs four [3%] in the placebo group) and anaemia (seven [5%] vs one [<1%]). Serious adverse events were reported in 25 (18%) patients who received olaparib and 11 (9%) who received placebo. Tolerability was similar in patients with mutated BRCA and the overall population. |
| Conclusions: | These results support the hypothesis that patients with platinumsensitive recurrent serous ovarian cancer with a BRCA mutation have the greatest likelihood of benefiting from olaparib treatment. |