LYNPARZA (olaparib) Approved in the EU for Germline BRCA-mutated Metastatic Pancreatic Cancer

AstraZeneca and Merck, known as MSD outside the United States and Canada, announced that LYNPARZA has been approved in the European Union (EU) as a monotherapy for the maintenance treatment of adult patients with germline BRCA1/2 mutations who have metastatic adenocarcinoma of the pancreas and have not progressed after a minimum of 16 weeks of platinum treatment within a first-line chemotherapy regimen.

The approval by the European Commission (EC) was based on results from the Phase 3 POLO trial, which were published in The New England Journal of Medicine. It follows the recommendation for approval by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA).

Pancreatic cancer is a rare, life-threatening disease with the lowest survival rate of the most common cancers. Approximately 5-7% of patients with metastatic pancreatic cancer have a germline BRCA mutation.

Dr. Hedy L. Kindler, co-principal investigator of the POLO trial and professor of medicine, University of Chicago Medicine, said, “Today’s approval opens the door to a new era of biomarker-led care for patients with metastatic pancreatic cancer in the EU, which has the highest incidence of any region globally. LYNPARZA now provides clinicians with a targeted, well-tolerated treatment option for patients with germline BRCA-mutated metastatic pancreatic cancer.”

Dave Fredrickson, executive vice president, oncology business unit, AstraZeneca, said, “Patients with metastatic pancreatic cancer historically have faced poor outcomes due to the aggressive nature of the disease and few treatment advances have been made over the last few decades. In the POLO trial, LYNPARZA nearly doubled median progression-free survival versus placebo after first-line chemotherapy for patients with germline BRCA-mutated metastatic pancreatic cancer. This approval underscores the importance of testing all patients for germline BRCA mutations at the time of diagnosis to help inform personalized treatment options for patients in the EU.”

Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories, said, “Merck and AstraZeneca are committed to advancing research into the treatment of patients with challenging types of cancer, including those with metastatic pancreatic cancer. LYNPARZA is now the only approved PARP inhibitor in biomarker-selected patients with metastatic pancreatic cancer. We look forward to making this targeted treatment option available for patients across the EU as quickly as possible.”

The POLO trial demonstrated that LYNPARZA nearly doubled the time patients with germline BRCA-mutated (gBRCAm) metastatic pancreatic cancer lived without disease progression or death to a median of 7.4 months versus 3.8 months on placebo (HR 0.53 [95% CI 0.35-0.81] p=0.0035).

The safety and tolerability profile of LYNPARZA in the POLO trial was consistent with previous trials. The most common adverse reactions (ARs) ≥10% were fatigue/asthenia (60%), nausea (45%), abdominal pain (34%), diarrhea (29%), anemia (27%), decreased appetite (25%), constipation (23%), vomiting (20%), back pain (19%), arthralgia (15%), rash (15%), thrombocytopenia (14%), dyspnea (13%), neutropenia (12%), nasopharyngitis (12%), dysgeusia (11%) and stomatitis (10%). The most common ≥ Grade 3 ARs were anemia (11%), fatigue/asthenia (5%), decreased appetite (3%), abdominal pain (2%), vomiting (1%) and arthralgia (1%). Among patients taking LYNPARZA, dose interruptions due to an AR of any grade occurred in 35% and dose reductions due to an AR occurred in 17%. Discontinuation due to ARs occurred in 6% of patients receiving LYNPARZA.

LYNPARZA is approved in the U.S. and several other countries as a first-line maintenance treatment for patients with gBRCAm metastatic pancreatic cancer whose disease has not progressed on at least 16 weeks of a first-line platinum-based chemotherapy regimen, based on the Phase 3 POLO trial, with ongoing regulatory reviews in other jurisdictions.