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Home All Specialties Obstetrics

Olaparib monotherapy may be effective in advanced BRCA-associated cancers

byMonica ParksandDavid Wang
November 8, 2014
in Obstetrics, Oncology
Reading Time: 3 mins read
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1. Olaparib monotherapy was associated with prolonged tumor response rate in advanced BRCA1/2-associated breast, ovarian, pancreatic, and prostate cancers.

2. Olaparib was well tolerated with common adverse side effects including anemia, fatigue, nausea, and vomiting.

Evidence Rating Level: 3 (Average)

Study Rundown: Olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, has previously demonstrated induction of DNA double-stranded breaks, targeting cells with DNA repair defects as seen in BRCA mutations. Olaparib has previously been identified as a potential treatment for BRCA1- and BRCA2-associated breast and ovarian cancers; however, the effect of olaparib on other BRCA-associated cancers is limited. The purpose of this phase II, open-label, non-comparative trial was to evaluate oral olaparib monotherapy in multiple BRCA1/2-associated cancers.

The trial prospectively followed over 290 patients with confirmed BRCA1/2 mutations and recurrent or refractory breast, pancreatic, ovarian, or prostate cancer. Patients were treated with oral olapraib 400 mg twice per day until disease progression and monitored monthly (28 days). At the conclusion of this trial, the authors found an overall 26.2% tumor response rate to olaparib monotherapy across the study cohort. Furthermore, 42% of patients had stable disease for 8 weeks or greater. Oral olaparib was relatively well tolerated, with anemia, fatigue, nausea and vomiting being the most commonly reported adverse effects. The results of this study support the use of BRCA-targeted therapy for malignancies regardless of anatomic origin. However, it should be noted that this was a phase II clinical trial not designed to compare olaparib to other therapies. Further studies with phase III trials will be required before olaparib can be used as a therapeutic option for these patients.

Click to read the study in JCO

Relevant Reading: Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer.

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In-Depth [randomized controlled trial]: This prospective, multi-center, non-comparative, open-labeled, phase II study of BRCA1/2 carriers with advanced cancer assessed tumor response to oral olaparib. Patients were eligible to participate if they had the following: platinum-resistant ovarian cancer, stage IV breast cancer with more than 3 chemotherapy trials, gemcitabine-resistant pancreatic cancer, or prostate cancer with progression on hormonal and systemic therapy. A total of 298 patients (193 with ovarian, 62 with breast, 23 with pancreatic, 8 with prostate cancer) were ultimately included in the final analysis, coming from 13 international centers. Median total duration of treatment was 166.5 days (range: 112.5-233.5 days). Tumor response rate was 26.2% overall (95% CI: 21.3-31.6) and 31.1% (95% CI: 24.6-38.1), 12.9% (95% CI: 5.7-23.9), 21.7% (95% CI: 7.5-43.7) and 50% (95% CI: 15.7-84.3) in ovarian, breast, pancreatic and prostate cancers, respectively. The most common adverse events were anemia, fatigue, nausea and vomiting.

More from this author: Rituximab linked with reduced chronic immune disease following stem cell transplantation, High-dose prophylaxis for hemophilia increases costs with minimal benefit, Ambrisentan found ineffective against idiopathic pulmonary fibrosis

 Image: PD

©2012-2014 2minutemedicine.com. All rights reserved. No works may be reproduced without expressed written consent from 2minutemedicine.com. Disclaimer: We present factual information directly from peer reviewed medical journals. No post should be construed as medical advice and is not intended as such by the authors, editors, staff or by 2minutemedicine.com. PLEASE SEE A HEALTHCARE PROVIDER IN YOUR AREA IF YOU SEEK MEDICAL ADVICE OF ANY SORT. 

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