| General information |
| Database: | DB00241 |
| Objective: | Prostate cancer is a heterogeneous disease, but current treatments are not based on molecular stratification. They hypothesized that metastatic, castrationresistant prostate cancers with DNArepair defects would respond to poly(adenosine diphosphate [ADP]ribose) polymerase (PARP) inhibition with olaparib. |
| Authors: | Mateo J, et al |
| Title: | DNARepair Defects and Olaparib in Metastatic Prostate Cancer. |
| Journal: | N Engl J Med |
| Year: | 2015 |
| PMID: | 26510020 |
| Trial Design |
| Clinical Trial Id: | NCT01682772 |
| Agent: | olaparib
|
| Target: | Poly [ADPribose] polymerase1
|
| Cancer Type: | prostate cancer |
| Cancer Subtype: | advanced castrationresistant prostate cancer |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | an openlabel, singlegroup, twostage, phase II, multisite study |
| Key Patients Feature: | patients with metastatic, castrationresistant prostate cancer |
| Biomarker: | homozygous deletions, deleterious mutations, or both in DNArepair genesincluding BRCA1/2, ATM, Fanconi's anemia genes, and CHEK2 |
| Biomark Analysis: | Nextgeneration sequencing identified homozygous deletions, deleterious mutations, or both in DNArepair genesincluding BRCA1/2, ATM, Fanconi's anemia genes, and CHEK2in 16 of 49 patients who could be evaluated (33%), including all 7 patients with BRCA2 loss (4 with biallelic somatic loss, and 3 with germline mutations) and 4 of 5 with ATM aberrations. The specificity of the biomarker suite was 94%. |
| Control Group Info: | single arm |
| Treatment Info: | pts were treated with olaparib tablets at a dose of 400 mg twice a day. Targeted nextgeneration sequencing, exome and transcriptome analysis, and digital polymerasechainreaction testing were performed on samples from mandated tumor biopsies. |
| Primary End Point: | the response rate, or as a reduction of at least 50% in the prostatespecific antigen level or a confirmed reduction in the circulating tumorcell count |
| Secondary End Point: | NA |
| Patients Number: | 50 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | 16 of 49 patients who could be evaluated had a response (33%; 95% confidence interval, 20 to 48), with 12 patients receiving the study treatment for more than 6 months. Of these 16 patients who could be evaluated (33%), 14 (88%) had a response to olaparib. |
| Disease Control Rate: | Of the 49 patients who could be evaluated, 32 (65%) had measurable disease at baseline according to RECIST, version 1.1; 6 of these patients (19%) had a confirmed radiologic partial response |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | Anemia (in 10 of the 50 patients [20%]) and fatigue (in 6 [12%]) were the most common grade 3 or 4 adverse events, findings that are consistent with previous studies of olaparib. |
| Conclusions: | Treatment with the PARP inhibitor olaparib in patients whose prostate cancers were no longer responding to standard treatments and who had defects in DNArepair genes led to a high response rate. |