James Gulley, MD, PhD, chief, Genitourinary Malignancies Branch, and director, Medical Oncology Service at the National Cancer Institute, discusses the take-home message with the combination of olaparib (Lynparza) plus durvalumab (Imfinzi) in metastatic castration-resistant prostate cancer (mCRPC).

A phase II study of olaparib and durvalumab presented at the 2018 Genitourinary Cancers Symposium aimed to see if the combination of a PARP inhibitor, olaparib, with a PD-L1 inhibitor, durvalumab, could lead to immune responses across an unselected group of patients. This included patients who did not have a DNA damage pathway mutation. Investigators reported that in the first 17 patients, the combination was safe and about half of the patients experience prostate-specific antigen (PSA) declines of at least 40%.

Gulley says that the take-home message from this research is that there is an early signal of activity for this combination, but the mechanism of action is not understood yet. Many of the patients who responded to the combination did not have DNA damage response pathway mutations, and next steps with this data will aim to understand the immune activity in this population.

Videos

James Gulley, MD, PhD, chief, Genitourinary Malignancies Branch, and director, Medical Oncology Service at the National Cancer Institute, discusses the take-home message with the combination of olaparib (Lynparza) plus durvalumab (Imfinzi) in metastatic castration-resistant prostate cancer.
 

Dr. Gulley on Take Home Message With Olaparib Plus Durvalumab in mCRPC

James Gulley, MD, PhD, chief, Genitourinary Malignancies Branch, and director, Medical Oncology Service, at the National Cancer Institute, discusses a phase II study of olaparib (Lynparza) and durvalumab (Imfinzi) in metastatic castration-resistant prostate cancer (mCRPC) in an unselected patient population, presented at the 2018 Genitourinary Cancers Symposium.

In prostate cancer, it has been found that immune checkpoint inhibition does not work as a single agent, with patients having minimal or no responses to PD-1 and PD-L1 agents, Gulley explains.

Studies have shown that patients who have a DNA damage response pathway mutation respond well to the PARP inhibitor olaparib, but patients who do not have a DNA damage response pathway mutation do not respond to this agent.

This study aimed to see if the combination of a PARP inhibitor, olaparib, with a PD-L1 inhibitor, durvalumab, could lead to immune responses across an unselected groups of patients, including patients who do not have a DNA damage response pathway mutation.

In the first 17 patients on the study, investigators found the combination was able to be given safely, and about half of the patients experienced PSA declines of at least 40%. Many of the patients had DNA damage response pathway mutations, but there were many patients who responded to the combination who did not have DNA damage response pathway mutations, Gulley notes.

James Gulley, MD, PhD

Articles

Dr. Gulley on Take Home Message With Olaparib Plus Durvalumab in mCRPC

Dr. Gulley Discusses a Phase II Study of Olaparib and Durvalumab in mCRPC