The FDA approved olaparib for the maintenance treatment of adult patients with germline BRCA-mutated metastatic pancreatic adenocarcinoma.
The FDA approved olaparib (Lynparza) for the maintenance treatment of adult patients with germline BRCA-mutated metastatic pancreatic adenocarcinoma whose disease has not progressed on at least 16 weeks of a first-line platinum-based chemotherapy regimen, according to AstraZeneca and Merck.1
The agent is now the only PARP inhibitor approved for this patient population, which follows a positive recommendation from the agency’s Oncologic Drugs Advisory Committee that previously voted 7 to 5 in favor of the approval.
“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. (olaparib) is now the only approved targeted medicine in biomarker-selected patients with advanced pancreatic cancer,” Dave Fredrickson, executive vice president, head of the oncology business unit, AstraZeneca, said in a press release.
The FDA made its decision based on data from the phase III POLO trial, which showed a progression-free survival (PFS) benefit with olaparib compared with placebo in this setting. In the randomized, double-blind, placebo-controlled trial, researchers evaluated the efficacy of olaparib as maintenance therapy in 154 patients who had a germline BRCA1 or BRCA2 mutation and metastatic pancreatic cancer, which had not progressed during first-line platinum-based chemotherapy.2
The median PFS with the PARP inhibitor was 7.4 months compared with 3.8 months with placebo (HR, 0.53; 95% CI, 0.35-0.81; P = .0035). In addition, after 2 years, 22.1% of patients had no disease progression versus 9.6% of those who received placebo.
Additional results showed that the objective response rate was 23.1% with olaparib compared with 11.5% in the placebo arm (odds ratio, 2.30); 11.1% (n = 2) of patients on olaparib achieved a complete response compared with 0 on placebo. The median duration of response was 24.9 months in the olaparib arm versus 3.7 months with placebo.
After 1 year, 33.7% of patients receiving olaparib showed no signs of disease progression compared with 14.5% of those who received a placebo.
Adverse events occurring in ≥10% of patients receiving olaparib included 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 frequent grade ≥3 AEs on the olaparib arm were anemia (11%), fatigue/asthenia (5%), decreased appetite (3%), abdominal pain (2%), vomiting (1%) and arthralgia (1%). AE-related dose interruptions occurred in 35% of the olaparib arm, with AE-related dose reductions occurring in 17% of this cohort. Six percent of the olaparib arm discontinued treatment due to AEs.
“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,” Julie Fleshman, president and CEO, Pancreatic Cancer Action Network, said in the release.
1. LYNPARZA® (olaparib) Approved by FDA as First-Line Maintenance Treatment of Germline BRCA-Mutated Metastatic Pancreatic Cancer. Merck. Published December 30, 2019. https://bit.ly/2ZDWX4R. Accessed December 30, 2019.
2. Golan T, Hammel P, Reni M, et al. Maintenance Olaparib for Germline BRCA-Mutated Metastatic Pancreatic Cancer. N Engl J Med. doi: 10.1056/NEJMoa1903387