A Combination Study of Durvalumab plus Olaparib in an Unselected Population with Metastatic Castrate-Resistant Prostate Cancer (mCRPC)
Abstract
Scientific Objective and Rationale: Approximately 25%–30% of advanced prostate cancers exhibit defects in DNA repair pathways. PARP inhibitors, such as olaparib, can have clinical efficacy in prostate cancer with mutations in DNA repair pathways. Increased DNA damage caused by olaparib may complement the activity of durvalumab, an immune checkpoint inhibitor. Based on this premise, it would be rational to combine these two drugs to determine whether they can improve clinical outcomes. In this study, tumors will be assessed for mutations, and patients’ immune cells will be analyzed. All patients will receive both drugs. Applicability of the Research: Patients with advanced prostate cancer may benefit from this new combination treatment, even if they don’t have a mutation in DNA repair pathways. This may result in a new therapy for unselected patients with metastatic disease. The study may also be helpful in determining predictive biomarkers for future studies. Treatment risks include side effects of both therapies, which are typically transient and can be managed with supportive measures. It may take months of treatment before patients experience changes in PSA, decreased pain, or changes in other clinical parameters. Career Goals in Prostate Cancer Research and Patient Care: When I joined the National Cancer Institute as a fellow in Hematology and Oncology, I had the opportunity to work with some of the leaders in the field of prostate cancer and immunotherapy, such as Dr. James L. Gulley. At the completion of my fellowship, I was retained as a Staff Clinician to be able to continue my clinical research, which I am passionate about. My goals in prostate cancer research and patient care include expanding available treatment options with DNA damage repair and immunotherapy combination studies. In the next phase of my career, my goal is to evaluate how treatments affect the immune system and how we can harness the immune system to fight cancer. The results of this research may lead to a better understanding of how these combination studies work together, which can lay the groundwork for future treatments for prostate cancer. Dr. James Gulley’s mentorship and career development support will aid me in developing alternative strategies for treating prostate cancer, particularly with immunotherapeutic agents. I will attend national meetings and educational sessions and reach out to meet new collaborators. I will meet quarterly with my mentorship committee to discuss the evolution of my project and important aspects of career development. Impact: The work proposed here could favorably impact men with advanced prostate cancer in a variety of ways. Men whose treatment options have been severely limited may benefit from a new therapy that could have clinical benefit. Positive findings from this study could serve as a proof of concept for future trials and could also help determine which patients are most likely to benefit from the combination of PARP inhibitors and immune checkpoint inhibitors.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810363
Entities
People
- Fatima Karzai
Organizations
- National Cancer Institute
- United States Army