Officials with the FDA have approved olaparib (Lynparza, AstraZeneca and Merck) for the maintenance treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) metastatic pancreatic adenocarcinoma whose disease has not progressed on at least 16 weeks of a first-line platinum-based chemotherapy regimen.
Officials with the FDA have approved olaparib (Lynparza, AstraZeneca and Merck) for the maintenance treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) metastatic pancreatic adenocarcinoma whose disease has not progressed on at least 16 weeks of a first-line platinum-based chemotherapy regimen, the companies announced Monday. According to Merck, patients will be selected for therapy based on an FDA-approved companion diagnostic for olaparib, a PARP inhibitor.
“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,” said Dave Fredrickson, executive vice president, head of the oncology business unit, AstraZeneca, in a prepared statement. “Lynparza is now the only approved targeted medicine in biomarker-selected patients with advanced pancreatic cancer.”
The drug’s approval was based on results from the pivotal phase 3 POLO trial published in the New England Journal of Medicine and presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting. Results showed a statistically significant and clinically meaningful improvement in progression-free survival (PFS), where olaparib 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 (HR 0.53 [95% CI 0.35-0.81] p=0.0035).
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 olaparib, dose interruptions due to an adverse reaction of any grade occurred in 35% and dose reductions due to an adverse reaction occurred in 17%. Discontinuation due to adverse reactions occurred in 6% of patients receiving the drug.
“Metastatic pancreatic cancer patients have been waiting a long time for new therapy options for their devastating disease. Today’s approval of Lynparza provides an exciting new treatment option for patients with germline BRCA-mutated metastatic pancreatic cancer,” said Julie Fleshman, president and CEO, Pancreatic Cancer Action Network, in a prepared statement.
Olaparib is approved in 65 countries for the maintenance treatment of platinum-sensitive relapsed ovarian cancer, regardless of BRCA status. It is approved in the United States and other countries as first-line maintenance treatment of BRCA-mutated advanced ovarian cancer following response to platinum-based chemotherapy. It is also approved in 44 countries, including the United States, for gBRCAm, HER2-negative metastatic breast cancer, previously treated with chemotherapy.
LYNPARZA® (olaparib) Approved by FDA as First-Line Maintenance Treatment of Germline BRCA-Mutated Metastatic Pancreatic Cancer [news release]. Kenilworth, NJ; December 30, 2019: Merck newsroom. https://www.mrknewsroom.com/news-release/oncology/lynparza-olaparib-approved-fda-first-line-maintenance-treatment-germline-brca-. Accessed December 30, 2019.