Lynparza (Olaparib) Achieves Positive Phase III Results as First-Line Maintenance Therapy in Germline BRCA-Mutated Metastatic Pancreatic Cancer

February 27, 2019/BioValleyBIOON/--UK pharmaceutical giantAstraZeneca(AstraZeneca) and its partner Merck & Co. recently jointly announced that the Phase III clinical study POLO, evaluating Lynparza (Chinese brand name: Lizhuo; generic name: olaparib) as first-line maintenance monotherapy for metastatic pancreatic cancer with germline BRCA mutations (gBRCAm), met its primary endpoint. Notably, these results make Lynparza the first PARP inhibitor to demonstrate a survival benefit in the treatment of gBRCAm metastatic pancreatic cancer in a Phase III clinical trial. In the United States, the FDA had previously granted orphan drug designation to Lynparza for the treatment of pancreatic cancer.

The POLO study was a randomized, double-blind, placebo-controlled, multicenter trial conducted in 154 patients with metastatic pancreatic cancer who carried germline BRCA mutations (gBRCAm) and whose disease had not progressed after first-line platinum-based chemotherapy. The study evaluated the efficacy and safety of Lynparza (300 mg twice daily) versus placebo as first-line maintenance monotherapy. Patients were randomized in a 3:2 ratio to receive either Lynparza or placebo until disease progression. The primary endpoint was progression-free survival (PFS), and key secondary endpoints included overall survival (OS), time to second disease progression, objective response rate, disease control rate, and health-related quality of life.

The results showed that, compared with the placebo group, the Lynparza treatment group demonstrated statistically significant and clinically meaningful improvement in progression-free survival (PFS), meeting the primary endpoint of the study. In this study, the safety and tolerability profile of Lynparza was consistent with that observed in previous studies. The full data from this study will be presented at an upcoming medicalConferencepublished above.

Jose Baselga, Executive Vice President of Oncology R&D at AstraZeneca, said: “The POLO study is the first positive Phase III study to evaluate any PARP inhibitor for the treatment of gBRCAm metastatic pancreatic cancer, a devastating disease with significant unmet medical needs. The results of the POLO study further demonstrate Lynparza’s efficacy in various BRCA mutationsTumorclinical efficacy in the type. We will discuss these results with global regulatory authorities as soon as possible.”

Roy Baynes, Senior Vice President of Merck Research Laboratories and Global Head of Clinical Development, as well as Chief Medical Officer, stated, “Clinical studies such as POLO demonstrate the shared commitment of MSD and AstraZeneca to evaluating treatment regimens for refractory cancers. The clinically meaningful results from this study will support the value of testing for germline BRCA mutations (gBRCAm) in patients with metastatic pancreatic cancer.”

Pancreatic cancer is the 12th most common cancer type globally, with 466,000 new cases in 2018 alone. gBRCAm pancreatic cancer accounts for 5-7% of all global cases. Pancreatic cancer is the fourth leading cause of cancer-related deaths and has the worst survival rate among the most common cancers, with a 5-year survival rate of less than 7% after diagnosis. Early diagnosis of pancreatic cancer is challenging, as patients are typically asymptomatic until the disease progresses to an advanced stage; approximately 80% of patients are diagnosed at the metastatic stage.DiagnosisExit.

Lynparza was approved in the United States in December 2014FDAApproved for market launch, it became the first PARP inhibitor approved globally. Lynparza is a first-in-class, oral PARP inhibitor that selectively kills cancer cells by exploiting defects in DNA repair pathways. This mechanism of action gives Lynparza the potential to treat a wide range of tumors with DNA repair deficiencies. PARP is associated with a broad spectrum of tumor types, especiallyBreast Cancerand ovarian cancer. Currently, AstraZeneca is conducting multiple clinical studies to investigate the use of Lynparza across a broad range ofTumorpotential, including breast cancer, prostate cancer, and pancreatic cancer.

AstraZeneca and MSD entered into a global strategic oncology collaboration in July 2017 to jointly develop and commercialize Lynparza and another MEK inhibitor, selumetinib, for the treatment of multiple typesTumorAstraZeneca has placed very high expectations on Lynparza, believing that the drug's annual sales will exceed $2 billion.

In the Chinese market, Lynparza (Lipuzhuo) was approved by the China National Drug Administration (CNDA) on August 23 this year for maintenance treatment of platinum-sensitive recurrent ovarian cancer. This approval makes Lynparza the first targeted therapy approved for ovarian cancer in China, marking the entry of ovarian cancer treatment in China into the era of PARP inhibitors. (Bioon.com)

Original Source:LYNPARZA? (olaparib) Reduced the Risk of Disease Progression or Death as First-Line Maintenance Treatment in Germline BRCA-Mutated Metastatic Pancreatic Cancer