Predicting Benefit From Olaparib Maintenance in Metastatic Pancreatic Cancer: The POLO Trial

Based on results from the POLO trial,^1,2 the BRACAnalysis CDx assay (Myriad Genetics) was able to identify patients with metastatic pancreatic cancer who benefitted from maintenance therapy with the poly [ADP ribose] polymerase (PARP) inhibitor olaparib, according to press announcements released on February 26, 2019.^1,3

The POLO study is a phase 3, randomized, controlled trial of olaparib monotherapy in 154 patients with metastatic pancreatic adenocarcinoma (with disease that had not progressed following first-line platinum-based chemotherapy) who were randomly assigned (3:2) to receive twice-daily administration of 300 mg of olaparib or placebo.^1,2 

All patients who were enrolled in the study had a deleterious or suspected deleterious germline BRCA1/2 mutation identified by the BRACAnalysis CDx assay. The primary end point of the POLO trial was progression-free survival, with overall survival, overall response rate, safety, and health-related quality of life included as secondary end points.

Results from the POLO trial showed that it met its primary end point of statistically significantly improvement in PFS when the olaparib arm was compared with the placebo arm. In addition, the safety and tolerability profiles of olaparib were similar to results observed in previous trials of this agent in other cancers.¹ 

“This is the first positive phase 3 trial of any PARP inhibitor in germline BRCA-mutated metastatic pancreatic cancer, a devastating disease with critical unmet need. The results of POLO provide further evidence of the clinical benefit of [olaparib] across a variety of BRCA-mutated tumor types. We will discuss these results with global health authorities as soon as possible,” said José Baselga, executive vice president, research and development, oncology at AstraZeneca.

The BRACAnalysis CDx test has previously received approval from the United States Food and Drug Administration (FDA) as a companion diagnostic assay for identifying patients with advanced breast and ovarian cancers who are candidates for the PARP inhibitor, olaparib.³

References

1. AstraZeneca. Lynparza significantly delayed disease progression as 1st-line maintenance treatment in germline BRCA-mutated metastatic pancreatic cancer [press release]. Published February 26, 2019. Accessed February 28, 2019.
2. ClinicalTrials.gov Identifier: NCT02184195. Olaparib in gBRCA mutated pancreatic cancer whose disease has not progressed on first line platinum-based chemotherapy (POLO). Updated January 29, 2019. Accessed February 28, 2019. 
3. Myriad. Myriad’s BRACAnalysis CDx^® test successfully identified patients with metastatic pancreatic cancer who benefitted from treatment with olaparib [press release]. Published February 26, 2019. Accessed February 28, 2019.