| General information |
| Database: | DB00240 |
| Objective: | Olaparib is an oral poly (ADPribose) polymerase inhibitor with activity in germline BRCA1 and BRCA2 (BRCA1/2) associated breast and ovarian cancers. They evaluated the efficacy and safety of olaparib in a spectrum of BRCA1/2associated cancers. |
| Authors: | Kaufman B, et al |
| Title: | Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation. |
| Journal: | J Clin Oncol |
| Year: | 2015 |
| PMID: | 25366685 |
| Trial Design |
| Clinical Trial Id: | NCT01078662 |
| Agent: | olaparib
|
| Target: | Poly [ADPribose] polymerase1
|
| Cancer Type: | advanced solid tumors |
| Cancer Subtype: | advanced cancer and a germline BRCA1/2 mutation. |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a multicenterphase II study |
| Key Patients Feature: | individuals with a germline BRCA1/2 mutation and recurrent cancer; eligibility included ovarian cancer resistant to prior platinum; breast cancer with more than and equal to three chemotherapy regimens for metastatic disease; pancreatic cancer with prior gemcitabine treatment; or prostate cancer with progression on hormonal and one systemic therapy. |
| Biomarker: | a germline BRCA1/2 mutation |
| Biomark Analysis: | as in the conclusion |
| Control Group Info: | single arm |
| Treatment Info: | Olaparib was administered at 400 mg twice per day. |
| Primary End Point: | tumor response rate. |
| Secondary End Point: | NA |
| Patients Number: | 298 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | The tumor response rate was 26.2% (78 of 298; 95% CI, 21.3 to 31.6) overall and 31.1% (60 of 193; 95% CI, 24.6 to 38.1), 12.9% (eight of 62; 95% CI, 5.7 to 23.9), 21.7% (five of 23; 95% CI, 7.5 to 43.7), and 50.0% (four of eight; 95% CI, 15.7 to 84.3) in ovarian, breast, pancreatic, and prostate cancers, respectively. |
| Disease Control Rate: | Stable disease more than and equal to 8 weeks was observed in 42% of patients (95% CI, 36.0 to 47.4), including 40% (95% CI, 33.4 to 47.7), 47% (95% CI, 34.0 to 59.9), 35% (95% CI, 16.4 to 57.3), and 25% (95% CI, 3.2 to 65.1) of those with ovarian, breast, pancreatic, or prostate cancer, respectively. |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | The most common adverse events (AEs) were fatigue, nausea, and vomiting. Grade more than and equal to 3 AEs were reported for 54% of patients; anemia was the most common (17%). |
| Conclusions: | Responses to olaparib were observed across different tumor types associated with germline BRCA12 mutations. Olaparib warrants further investigation in confirmatory studies |