FDA Approves Maintenance Olaparib for Metastatic Pancreatic Cancer

Officials with the FDA recently approved olaparib (Lynparza, Merck and AstraZeneca) for the maintenance treatment of adult patients with germline BRCA-mutated metastatic pancreatic cancer, according to a press release.¹

With this approval, olaparib is the first poly adenosine diphosphate-ribose polymerase (PARP) inhibitor approved for this indication. 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 are eligible for this therapy.¹

Survival results are based on the phase 3 POLO clinical trial, which demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS). The study included 154 randomized patients who were assigned to receive either olaparib or placebo.²

According to the data, treatment with olaparib nearly doubled the time patients with 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). An interim analysis of overall survival (OS), at a data maturity of 46%, showed no difference between the olaparib and placebo groups (median, 18.9 months versus 18.1 months; hazard ratio for death, 0.91; 95% CI, 0.56 to 1.46; P=0.68). Additionally, the study showed no significant between-group difference in health-related quality of life.²

The incidence of grade 3 or higher adverse events (AEs) was 40% in the olaparib group and 23% in the placebo group, and 5% and 2% of the patients, respectively, discontinued the trial intervention due to an AE. The most common AEs were fatigue/asthenia, nausea, abdominal pain, diarrhea, anemia, decreased appetite, constipation, vomiting, back pain, arthralgia, rash, thrombocytopenia, dyspnea, neutropenia, nasopharyngitis, dysgeusia, and stomatitis.²

“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,” Dave Fredrickson, executive vice president, head of oncology business unit at AstraZeneca, said in a statement.¹ “Lynparza is now the only approved targeted medicine in biomarker-selected patients with advanced pancreatic cancer.”

Olaparib is also indicated for the maintenance treatment of platinum-sensitive relapsed ovarian cancer, regardless of BRCA status; first-line maintenance treatment of BRCA-mutated advanced ovarian cancer following response to platinum-based chemotherapy; and gBRCAm, human epidermal growth factor receptor 2-negative metastatic breast cancer previously treated with chemotherapy.¹

References:

1. Lynparza (olaparib) Approved by FDA as First-Line Maintenance Treatment of Germline BRCA-Mutated Metastatic Pancreatic Cancer [news release]. Merck’s website. https://www.mrknewsroom.com/news-release/oncology/lynparza-olaparib-approved-fda-first-line-maintenance-treatment-germline-brca-. Accessed January 2, 2020.
2. Golan T, Hammel P, Reni M, et al. Maintenance Olaparib for Germline BRCA-Mutated Metastatic Pancreatic Cancer. The New England Journal of Medicine. 2019. Doi: 10.1056/NEJMoa1903387.