| General information |
| Database: | DB00520 |
| Objective: | Olaparib (AZD2281) is an oral poly(adenosine diphosphate [ADP]ribose) polymerase inhibitor that has shown antitumor activity in patients with highgrade serous ovarian cancer with or without BRCA1 or BRCA2 germline mutations. |
| Authors: | Ledermann J, et al |
| Title: | Olaparib maintenance therapy in platinumsensitive relapsed ovarian cancer. |
| Journal: | N Engl J Med. |
| Year: | 2012 |
| PMID: | 22452356 |
| Trial Design |
| Clinical Trial Id: | NCT00753545 |
| Agent: | olaparib
|
| Target: | Poly [ADPribose] polymerase1
|
| Cancer Type: | ovarian, primary peritoneal, or fallopian tube carcinoma |
| Cancer Subtype: | advanced ovarian or fallopian tube cancer or primary peritoneal cancer |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | a randomized, doubleblind, placebocontrolled, phase II study |
| Key Patients Feature: | Patients were eligible if were 18 years of ageor older and had recurrent ovarian or fallopiantube cancer or primary peritoneal cancer with highgrade (grade 2 or 3) serous features or a serouscomponent, which was platinumsensitive (definedby an objective response to a previous platinumbased therapy for more than 6 months). Eligiblepatients had completed at least two courses ofplatinumbased chemotherapy, and their most recent regimen induced an objective response as defined by the Response Evaluation Criteria in SolidTumors (RECIST) guidelines, version 1.0, 27 or acancer antigen 125 (CA125) response, accordingto Gynecological Cancer InterGroup criteria28 (seethe Supplementary Appendix, available with thefull text of this article at NEJM.org). The studydesign is shown in Figure 1. Other key inclusioncriteria were CA125 measurements before treatment that were below the upper limit of the normal range (in the case of values above this limit, any increase in a second sample, obtained morethan 7 days later, had to be less than a 15% increasefrom the first sample). BRCA1/2 mutation statuswas not required. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | olaparib VS placebo |
| Treatment Info: | Patients were randomly assigned to receive olaparib, at a dose of 400 mg twice daily, or placebo. |
| Primary End Point: | progression free survival according to the Response Evaluation Criteria in Solid Tumors guidelines. |
| Secondary End Point: | NA |
| Patients Number: | 265 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | progression free survival was significantly longer with olaparib than with placebo (median, 8.4 months vs. 4.8 months from randomization on completion of chemotherapy; hazard ratio for progression or death, 0.35; 95% confidence interval [CI], 0.25 to 0.49; P<0.001). |
| Median OS A vs. C: | The median overall survival was similar in the two study groups (29.7 months in the olaparib group and 29.9 months in the placebo group). |
| Adverse Event(agent arm): | Adverse events more commonly reported in the olaparib group than in the placebo group (by more than 10% of patients) were nausea (68% vs. 35%), fatigue (49% vs. 38%), vomiting (32% vs. 14%), and anemia (17% vs. 5%); the majority of adverse events were grade 1 or 2. |
| Conclusions: | Olaparib as maintenance treatment significantly improved progression free survival among patients with platinumsensitive, relapsed, highgrade serous ovarian cancer. Interim analysis showed no overall survival benefit. The toxicity profile of olaparib in this population was consistent with that in previous studies. |