| General information |
| Database: | DB01045 |
| Objective: | Oral poly(ADPribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer |
| Authors: | Andrew Tutt |
| Title: | Oral poly(ADPribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: a proofofconcept trial. |
| Journal: | lancet |
| Year: | 2010 |
| PMID: | 20609467 |
| Trial Design |
| Clinical Trial Id: | NCT00494234 |
| Agent: | olaparib
|
| Target: | Poly [ADPribose] polymerase1
|
| Cancer Type: | breast cancer |
| Cancer Subtype: | breast cancer |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a nonrandomised, sequential cohort design, and was undertaken prospectively in I6 centres in Australia, Germany, Spain, Stheyden, the UK, and the USA. |
| Key Patients Feature: | Eligible women were aged 18 years or older and had locally advanced breast cancer (not amenable to curative surgery or radiation) or metastatic breast cancer (stage IIIB/IIIC or IV according to the American Joint Committee on Cancer Criteria) with one or more measurable lesions according to the Response Evaluation Criteria In Solid Tumours (RECIST). All patients were required to have a germline BRCA1 or BRCA2 mutation that was confi rmed to be deleterious by analysis at an external central reference laboratory (Myriad Genetic Laboratories, Salt Lake City, UT, USA). All patients had been given at least one chemotherapy regimen, had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, and had an estimated life expectancy of at least 16 weeks. Patients whose tumours were hormonereceptor positive had been given at least one regimen of hormonal therapy. |
| Biomarker: | BRCA1 or BRCA2 mutations |
| Biomark Analysis: | NA |
| Control Group Info: | olaparib 100 mg twice daily |
| Treatment Info: | The fi rst cohort (n=27) was given continuous oral olaparib at the maximum tolerated dose (400 mg twice daily), and the second (n=27) was given a lotheyr dose (100 mg twice daily). |
| Primary End Point: | objective response rate (ORR). |
| Secondary End Point: | NA |
| Patients Number: | 54 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | ORR was 11 (41%) of 27 patients (95% CI 25-59) in the cohort assigned to 400 mg twice daily, and six (22%) of 27 (11-41) in the cohort 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): | The most frequent causally related adverse events in the cohort given 400 mg twice daily were fatigue (grade 1 or 2, 11 [41%]; grade 3 or 4, four [15%]), nausea (grade 1 or 2, 11 [41%]; grade 3 or 4, four [15%]), vomiting (grade 1 or 2, three [11%]; grade 3 or 4, three [11%]), and anaemia (grade 1 or 2, one [4%]; grade 3 or 4, three [11%]). |
| Conclusions: | The results of this study provide positive proof of concept for PARP inhibition in BRCAdefi cient breast cancers and shows a favourable therapeutic index for a novel targeted treatment strategy in patients with tumours that have genetic loss of function of BRCA1associated or BRCA2associated DNA repair. Toxicity in women with BRCA1 and BRCA2 mutations was similar to that reported previously in those without such mutations. |