by Dr. C.H. Weaver M.D. updated 3/2019
Lynparza (olaparib) delays cancer progression and improves survival when used to treat BRCA-mutated pancreatic cancer and appears to represent a new treatment option for this hard to treat cancer. (1-4)
The US Food and Drug Administration (FDA) had recently announced that they were granting orphan drug designation for Lynparza based on the results of the POLO clinical trial.
About BRCA Mutated Pancreatic Cancer
Pancreatic cancer has the worst survival rate of the most common cancers and less than seven percent of patients survive more than five years after diagnosis. Germline BRCA-mutated pancreatic cancer accounts for ~7% of all pancreatic cancers.(2)
BRCA1 and BRCA2 are human genes that produce proteins responsible for repairing damaged DNA. When either of these genes is mutated, or altered DNA damage may not be repaired properly, and the cells are more likely to develop additional genetic alterations that can lead to cancer.
Each year, approximately 43,000 people are diagnosed with pancreatic cancer in the United States and close to 37,000 die from the disease. The disease is often diagnosed at an advanced stage, treatment remains challenging, and new treatment approaches are required.
About the POLO Clinical Trial
The POLO clinical trial evaluated the effectiveness of Lynparza tablets as 1st-line maintenance therapy in 154 patients with gBRCAm metastatic pancreatic cancer whose disease had not progressed following treatment with 1st-line platinum-based chemotherapy. Patients were treated with Lynparza or placebo and directly compared and the initial trial results report that Lynparza significantly delays cancer progression.
Lynparza is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated for the treatment of selected patients with ovarian, fallopian tube, or primary peritoneal cancer. The PARP enzyme plays a role in DNA repair, including the repair of DNA damage from chemotherapy. Precision cancer medicines that target and inhibit this enzyme may contribute to cancer cell death and increased sensitivity to chemotherapy and are called PARP inhibitors. By blocking this enzyme, DNA inside the cancerous cells is less likely to be repaired, leading to cell death and possibly a slow-down or stoppage of tumor growth.
The use of Lynparza in pancreatic cancer is being assessed in the ongoing Phase III POLO trial, which is testing Lynparza as maintenance monotherapy vs placebo in patients with germline BRCA-mutated metastatic pancreatic cancer whose disease has not progressed following 1st-line platinum-based chemotherapy. Results from the POLO trial are expected in the first half of 2019.