AstraZeneca and MSD Inc. (known as Merck & Co., Inc. inside the U.S. and Canada) announced that Lynparza (olaparib) has been approved by the U.S. Food and Drug Administration (FDA) in the U.S. for the maintenance treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) metastatic pancreatic adenocarcinoma (pancreatic cancer) whose disease has not progressed on at least 16 weeks of a 1st-line platinum-based chemotherapy regimen. Patients will be selected for therapy based on an FDA-approved companion diagnostic for Lynparza. The approval follows the recommendation from the FDA Oncologic Drugs Advisory Committee (ODAC) on Dec. 17 for Lynparza in this indication, and was based on results from the pivotal Phase III POLO trial published in The New England Journal of Medicine and presented at the 2019 American Society of Clinical Oncology Annual Meeting.
Results showed a statistically significant and clinically meaningful improvement in progression-free survival, where Lynparza nearly doubled the time patients with gBRCAm metastatic pancreatic cancer lived without disease progression or death to a median of 7.4 months vs. 3.8 months on placebo. The safety and tolerability profile of Lynparza in the POLO trial was in line with that observed in prior clinical trials.
Dave Fredrickson, Executive Vice President, Oncology Business Unit, said, “Patients with advanced pancreatic cancer historically have faced poor outcomes due to the aggressive nature of the disease and limited treatment advances over the last few decades. Lynparza is now the only approved targeted medicine in biomarker-selected patients with advanced pancreatic cancer.”
Hedy L. Kindler, Co-Principal Investigator of the POLO trial and Professor of Medicine, University of Chicago Medicine, said, “Today’s approval of olaparib based on the POLO results gives clinicians an important 1st-line maintenance treatment option which nearly doubled the progression-free survival benefit in patients with germline BRCA-mutated metastatic pancreatic cancer.”
Based on the results of POLO, the National Comprehensive Cancer Network (NCCN) guidelines were updated in July 2019 to recommend Lynparza as maintenance treatment for gBRCAm pancreatic cancer. In the U.S., eligible metastatic pancreatic cancer patients will be selected for therapy based on the FDA-approved companion diagnostic, BRACAnalysis CDx, a genetic test that detects the presence of a BRCA1 or BRCA2 gene mutation. BRACAnalysis CDx is owned and commercialized by Myriad Genetics, Inc.
BRCA1 and BRCA2 (breast cancer susceptibility genes 1/2) are human genes that produce proteins responsible for repairing damaged DNA and play an important role in maintaining the genetic stability of cells. When either of these genes is mutated, or altered, such that its protein product either is not made or does not function correctly, DNA damage may not be repaired properly, and cells become unstable. As a result, cells are more likely to develop additional genetic alterations that can lead to cancer.