| General information |
| Database: | DB00524 |
| Objective: | Olaparib is a novel, orally active poly(ADPribose) polymerase (PARP) inhibitor that induces synthetic lethality in homozygous BRCAdeficient cells. They aimed to assess the efficacy and safety of olaparib for treatment of advanced ovarian cancer in patients with BRCA1 or BRCA2 mutations. |
| Authors: | Audeh MW, et al |
| Title: | Oral poly(ADPribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer: a proofofconcept trial. |
| Journal: | Lancet. |
| Year: | 2010 |
| PMID: | 20609468 |
| Trial Design |
| Clinical Trial Id: | NCT00494442 |
| Agent: | olaparib
|
| Target: | Poly [ADPribose] polymerase1
|
| Cancer Type: | ovarian, primary peritoneal, or fallopian tube carcinoma |
| Cancer Subtype: | epithelial ovarian, primary peritoneal, or fallopian tube carcinoma |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | prospective, multicentre, phase II study |
| Key Patients Feature: | Women (aged more than and equal to 18 years) were enrolled if they had recurrentepithelial ovarian cancer, primary peritoneal or fallopiantube carcinoma, and one or more measurable lesionsaccording to the Response Evaluation Criteria In SolidTumors (RECIST).21 All patients needed to have a germlineBRCA1 or BRCA2 mutation that was confi rmed by analysisat an external central reference laboratory (Myriad GeneticLaboratories, Salt Lake City, UT, USA). All patients neededto have tumours that had recurred after a previouschemotherapy regimen, have an Eastern CooperativeOncology Group (ECOG) performance status of 0-2, andan estimated life expectancy of at least 16 weeks. |
| Biomarker: | genetic BRCA1 or BRCA2 mutations |
| Biomark Analysis: | Findings from thisphase 2 study provide positive proof of concept of the efficacy and tolerability of genetically targeted treatment with olaparib in BRCAmutated advanced ovarian cancer. |
| Control Group Info: | first cohort (n=33) was given continuous oral olaparib at the maximum tolerated dose of 400 mg twice daily, and the second cohort (n=24) was given continuous oral olaparib at 100 mg twice daily. |
| Treatment Info: | The first cohort (n=33) was given continuous oral olaparib at the maximum tolerated dose of 400 mg twice daily, and the second cohort (n=24) was given continuous oral olaparib at 100 mg twice daily. |
| Primary End Point: | objective response rate (ORR). |
| Secondary End Point: | NA |
| Patients Number: | 57 |
| Trial Results |
| DLT_MTD: | In patients given olaparib 400 mg twice daily, the most frequent causally relatedadverse events were nausea (grade 1 or 2, 14 [42%]; grade 3 or 4, two [6%]), fatigue (grade 1 or 2, ten [30%]; grade 3 or4, one [3%]), and anaemia (grade 1 or two, fi ve [15%]; grade 3 or 4, one [3%]). The most frequent causally relatedadverse events in the cohort given 100 mg twice daily were nausea (grade 1 or 2, seven [29%]; grade 3 or 4, two [8%])and fatigue (grade 1 or 2, nine [38%]; none grade 3 or 4). |
| Objective Response Rate: | ORR was 11 (33%)of 33 patients (95% CI 20-51) in the cohort assigned to olaparib 400 mg twice daily, and three (13%) of 24 (4-31) in thecohort assigned to 100 mg twice daily |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | In patients given olaparib 400 mg twice daily, the most frequent causally related adverse events were nausea (grade 1 or 2, 14 [42%]; grade 3 or 4, two [6%]), fatigue (grade 1 or 2, ten [30%]; grade 3 or 4, one [3%]), and anaemia (grade 1 or two, five [15%]; grade 3 or 4, one [3%]). The most frequent causally related adverse events in the cohort given 100 mg twice daily were nausea (grade 1 or 2, seven [29%]; grade 3 or 4, two [8%]) and fatigue (grade 1 or 2, nine [38%]; none grade 3 or 4). |
| Conclusions: | Findings from thisphase 2 study provide positive proof of concept of the efficacy and tolerability of genetically targeted treatment with olaparib in BRCAmutated advanced ovarian cancer. |