Lynparza Approved for Advanced Pancreatic Cancer

The Food and Drug Administration granted approval for AstraZeneca and Merck’s Lynparza (olaparib) as a first-line maintenance therapy in adult patients with germline BRCA-mutated metastatic pancreatic cancer.

Specifically, the drug is approved for patients whose disease has not advanced during at least 16 weeks of a first-line platinum-based chemotherapy regimen.

The approval follows the Phase III POLO trial, which was published in The New England Journal of Medicine. The randomized, double-blind, placebo-controlled trial. Patients with a germline BRCA1 or BRCA2 mutation and metastatic pancreatic disease with no progression during first-line platinum-based chemotherapy. Patients were randomized 3:2 to either maintenance olaparib 300 mg twice a day or placebo. The main outcome measure was progression-free survival.

The study authors evaluated 3,315 patients for potential inclusion, of whom 154 were randomized: 92 to olaparib and 62 to placebo. The olaparib group had significantly longer median progression-free survival compared to the placebo group (7.4 months vs. 3.8 months; hazard ratio [HR] for disease progression or death=0.53; 95% confidence interval [CI], 0.35-0.82; P=0.004). Upon interim analysis of overall survival when data maturity was at 46%, olaparib and placebo patients did not largely differ (median 18.9 months vs. 18.1 months; HR for death=0.91; 95% CI, 0.56-1.46; P=0.68). Health-related quality of life was measured using the global quality-of-life score on a 100-point scale, with higher scores indicating a better quality of life, per the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire; the outcomes did not largely differ (between-group difference, –2.47 points; 95% CI, –7.27 to 2.33). The olaparib patients had a higher incidence of grade 3 or higher adverse events (AEs) than the placebo group (40% vs. 23%; between-group difference, 16 percentage points; 95% CI, –0.02 to 31), and more olaparib patients than placebo patients discontinued treatment due to an AE (5% vs 2%).

“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 of the Pancreatic Cancer Action Network, in a press release.

According to the same press release, “The most common adverse reactions (ARs) ≥10% were fatigue (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%), nasopharyngitis (12%), neutropenia (12%), dysgeusia (11%) and stomatitis (10%). Grade 3 or above ARs were anemia (11%), fatigue (5%), neutropenia (4%), decreased appetite (3%), thrombocytopenia (3%), abdominal pain (2%), vomiting (1%) and arthralgia (1%). ARs led to dose reduction in 17% of patients on LYNPARZA while 6% of patients discontinued treatment.”