The phase 3 POLO trial is the first randomized study to establish a biomarker-driven approach in the treatment of metastatic pancreatic cancer.
Maintenance therapy with Lynparza (olaparib) significantly delayed disease progression in patients with germline BRCA-mutated metastatic pancreatic cancer, according to results from the phase 3 POLO trial presented at the 2019 American Society of Clinical Oncology Annual Meeting.
“POLO is the first phase 3 randomized study to establish a biomarker-driven approach in the treatment of metastatic pancreatic cancer, and it opens the door to a new era of personalized care for this difficult-to-treat cancer,” lead study author Dr. Hedy L. Kindler, professor of medicine at the University of Chicago Medicine, said in a press release. “Roughly one in five patients responded to olaparib for a median of two years, which is truly remarkable for metastatic pancreatic cancer. For patients with BRCA-driven metastatic pancreatic cancer, we may be seeing a change in patients’ disease trajectory.”
In the randomized, double-blind, placebo-controlled, phase 3 trial, researchers evaluated the efficacy of Lynparza 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.
The primary endpoint was progression-free survival — or the time from treatment to disease worsening. Secondary endpoints were overall survival, time from randomization to second progression or death, objective response rate, disease control rate, safety and tolerability.
Median progression-free survival with the PARP inhibitor was 7.4 months compared with 3.8 months with placebo. In addition, after two years, 22.1% of patients had no disease progression versus 9.6% of those who received placebo.
Median progression-free survival was consistent irrespective of response to prior platinum-based chemotherapy, and at six, 12, 18 and 24 months, the percentage of patients who were progression-free in the olaparib arm was more than twice that in the placebo arm.
The overall response rate was 23.1% with Lynparza compared with 11.5% in the placebo arm. Two patients treated with Lynparza had a complete response, both of which were ongoing at data cutoff. The median duration of response was 24.9 months in the Lynpaarza arm versus 3.7 months with placebo.
After one year, 33.7% of patients receiving Lynparza showed no signs of disease progression compared with 14.5% of those who received a placebo.
An interim analysis of overall survival at data maturity of 46% demonstrated no difference between arms.
In addition, the researchers saw no significant difference in health-related quality of life.
There were no new safety signals with Lynparza. Grade 3 or higher side effects occurred in 40% of patients in the Lynparza arm compared with 23% of those in the placebo arm. In total, 5.5% and 1.7% of patients, respectively, discontinued treatment due to a side effect.
“We are eagerly awaiting longer-term data to understand the full impact of the results from this trial. It’s encouraging to see that olaparib is consistently delaying the progression of metastatic pancreatic cancer in patients with a BRCA mutation. We’re potentially on the cusp of a new age of treatment for pancreatic cancer, where for the first time we can tailor therapy based on a biomarker and where having a BRCA mutation opens up more treatment options,” said ASCO expert Dr. Suzanne Cole.