AACR, Author Interviews, Biomarkers, Cancer Research / 22.04.2015
PARP Inhibitor Combo For Cancer Patients With and Without BRCA Mutation
MedicalResearch.com Interview with:
Timothy Yap, MD, PhD, NIHR BRC
The Institute of Cancer Research and
The Royal Marsden NHS Foundation Trust
London, United Kingdom.
Medical Research: What is the background for this study? What are the main findings?
Dr. Yap: This is a novel phase I trial assessing for the first time if the PARP inhibitor olaparib can be combined with the AKT inhibitor AZD5363. The study was undertaken at the Royal Marsden and The Institute of Cancer Research in London, England. This targeted combination was based on strong preclinical rationale demonstrating synergy between both drugs in BRCA positive tumors and also antitumor activity in non-BRCA positive tumors. Although olaparib was recently approved by the FDA for treating advanced ovarian cancer associated with defective BRCA genes, antitumor efficacy in different non-BRCA tumors is yet to be established.
The key finding for this study was that it was indeed possible to combine both drugs safely, with multiple patients with different cancers responding, including patients with and without BRCA1/2 mutations. We also assessed a new intrapatient dose escalation phase I trial design in this study, and demonstrated that the novel design could be successfully implemented, with completion of the dose escalation phase in 2 schedules of the combination with just 20 patients in 7.5 months.
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