| General information |
| Database: | DB00513 |
| Objective: | 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: | prospective, multicenter, nonrandomizedphase II study |
| Key Patients Feature: | Individuals(age 18years)withaconfirmedgermlinelossoffunctionBRCA1 or BRCA2 mutation deemed deleterious or suspected deleterious bylocal practice before consent and advanced solid tumor were enrolled. Eligibility criteria included one measurable or evaluable lesion according toRECIST (version 1.1), Eastern Cooperative Oncology Group performancestatusof0to2, andlifeexpectancy 16weeks.Furthereligibilityincludedoneof the following: platinumresistant (relapse within 6 months of platinumtherapy) epithelial ovarian, primary peritoneal, or fallopian tube cancer (orunsuitable for further platinum therapy); breast cancer with progression despite threepreviouslinesofchemotherapy(hormonereceptor-positiveandhuman epidermal growth factor receptor 2-positive patients also had to havenot responded to hormonal and trastuzumab therapy, respectively, in advancedsetting);pancreaticcancerwithprogressionduringgemcitabinetreatment in the advanced setting (or felt to be unsuitable for gemcitabine);hormonerefractory prostate cancer with two consecutive rising prostatespecific antigen (PSA) values above their nadir, progression despite onesystemic therapy course, and no anti-androgen therapy for 6 weeks beforestudy entry; and other tumor types with progression despite one therapycourse in the metastatic setting. |
| Biomarker: | a germline BRCA1/2 mutation |
| Biomark Analysis: | Median total duration of olaparib treatment was 166.5 days, ranging from 112.5 to 223.5 days for patients with breast and prostate cancers, respectively. |
| 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: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | Median PFS was 7, 3.7, 4.6, and 7.2 months in the ovarian, breast, pancreatic, and prostate cancer groups, respectively. |
| Median OS A vs. C: | Median OS was 16.6, 11, 9.8, and 18.4 months in the ovarian, breast, pancreatic, and prostate groups, respectively. |
| Adverse Event(agent arm): | The most common adverse events (AEs) were fatigue, nausea, and vomiting. Grade 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. |