| General information |
| Database: | DB00521 |
| Objective: | They assessed the comparative efficacy and safety of olaparib and pegylated liposomal doxorubicin (PLD) in this patient population. |
| Authors: | Kaye SB, et al |
| Title: | Phase II, openlabel, randomized, multicenter study comparing the efficacy and safety of olaparib, a poly (ADPribose) polymerase inhibitor, and pegylated liposomal doxorubicin in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer. |
| Journal: | J Clin Oncol. |
| Year: | 2012 |
| PMID: | 22203755 |
| Trial Design |
| Clinical Trial Id: | NCT00628251 |
| 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, multicenter, openlabel, randomized, phase II study |
| Key Patients Feature: | Women age 18 years with histologically or cytologically confirmedrecurrent epithelial ovarian, primary peritoneal, or fallopian tube carcinomaand one or more measurable lesions according to Response Evaluation Criteria In Solid Tumors (RECIST) were enrolled.15 Patients had a confirmedgermline BRCA1/2 mutation, disease that recurred or progressed within 12months of the most recent platinumbased chemotherapy regimen (anothernonPLD chemotherapy after this was permitted), an Eastern CooperativeOncology Group performance status of 0 to 2, and estimated life expectancyof 16 weeks. Additional eligibility criteria included adequate bone marrow, renal, and hepatic function. |
| Biomarker: | BRCA1 or BRCA2 mutations |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | Patients were assigned in a 1:1:1 ratio to olaparib 200 mg twice per day or 400 mg twice per day continuously or PLD 50 mg/m(2) intravenously every 28 days. |
| Primary End Point: | Response Evaluation Criteria in Solid Tumors (RECIST) assessed progression free survival (PFS). |
| Secondary End Point: | objective response rate (ORR) and safety. |
| Patients Number: | 97 |
| Trial Results |
| DLT_MTD: | Olaparib 400 mg twice per day is a suitable dose to explore |
| Objective Response Rate: | RECISTassessed ORRs were 25%, 31%, and 18% for olaparib 200 mg, olaparib 400 mg, and PLD, respectively; differences were not statistically significant. |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | Median PFS was 6.5 months (95% CI, 5.5 to 10.1 months), 8.8 months (95% CI, 5.4 to 9.2 months), and 7.1 months (95% CI, 3.7 to 10.7 months) for the olaparib 200 mg, olaparib 400 mg, and PLD groups, respectively. |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | The most common AEs in the olaparib groups were generally CTCAE grade 2 fatigue, GI symptoms, anemia, and rash; these were seen more commonly at olaparib 400 mg. The most commonly reported AEs in the PLD group were nausea, stomatitis, and fatigue. The incidence of CTCAE grade 3 or 4 events was low; were more frequent in patients receiving PLD and included stomatitis, palmarplantar erythrodysesthesia, and rash, although grade 3 anemia was seen more frequently in patients receiving olaparib 400 mg (13%).olaparib 400 mg (13%). |
| Conclusions: | The efficacy of olaparib was consistent with previous studies. Hotheyver, the efficacy of PLD was greater than expected. Olaparib 400 mg twice per day is a suitable dose to explore in further studies in this patient population. |