Donald A. Richards, MD, PhD, medical oncologist, Texas Oncology, discusses the use of genetic testing in patients with metastatic pancreatic cancer.

Results from the phase III POLO trial showed a significant improvement in progression-free survival with olaparib (Lynparza) maintenance therapy in patients with advanced germline 

-mutated disease who did not progress on platinum-based chemotherapy. As such, the National Comprehensive Cancer Network guidelines recommend to test patients with advanced metastatic pancreatic cancer for 

With these recommendations in place, genetic testing is becoming more widespread in pancreatic cancer. However, the role of testing for somatic mutations is not as well defined, says Richards. Additionally, several challenges have made testing difficult to adopt routinely, including the availability of tissue and cost of mutational analysis, concludes Richards.

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Donald A. Richards, MD, PhD, discusses the use of genetic testing in patients with metastatic pancreatic cancer.

Dr. Richards on Genetic Testing in Metastatic Pancreatic Cancer

Donald A. Richards, MD, PhD, medical oncologist, Texas Oncology, discusses the secondary endpoints of the randomized, double-blind, phase III POLO trial, which evaluated maintenance therapy with olaparib (Lynparza) in patients with germline 

Secondary endpoints include overall survival, time to second progression or death,objective response rate, disease control rate, safety, and tolerability.

After 24-months, 33.7% of patients treated with olaparib showed no signs of disease progression compared with 14.5% of patients in the placebo arm. The risk of disease progression with olaparib was reduced by 47% (HR, 0.53) versus placebo.

Olaparib was generally well tolerated and quality of life was not compromised as a result of treatment. Grade ≥3 adverse events (AEs) were reported in 40% of patients on olaparib compared with 23% of those in the placebo arm. Notably, 5.5% and 1.7% of patients discontinued treatment due to an AE in the olaparib and placebo arms, respectively.

Results from the POLO trial have had a significant impact on the treatment paradigm. Olaparib induced a significant response rate and demonstrated durable responses in this space, Richards concludes. This highlights the need for genetic testing to identify patients with 

Donald A. Richards, MD, PhD, discusses the secondary endpoints of the randomized, double-blind, phase III POLO trial, which evaluated maintenance therapy with olaparib in patients with germline BRCA-mutated, metastatic pancreatic cancer.
 

Dr. Richards on Secondary Endpoints of the POLO Trial in Pancreatic Cancer

Donald A. Richards, MD, PhD, medical oncologist, Texas Oncology, discusses the potential benefits of PARP inhibitors in patients with metastatic pancreatic cancer who harbor somatic 

In the randomized phase III POLO trial, investigators reported a significant progression-free survival benefit with the addition of olaparib (Lynparza) maintenance therapy in patients with germline 

 mutations (7.4 months vs 3.8 months with placebo).

After screening 3315 patients with metastatic pancreatic cancer, investigators discovered that approximately 7.5% of patients had a germline 

 mutation, Richard says. However, the effect of PARP inhibitors on patients with somatic mutations is unknown.

According to Richards, future tests exploring the potential benefit of olaparib and other PARP inhibitors in patients with mutations in 

Donald A. Richards, MD, PhD, discusses the potential benefits of PARP inhibitors in patients with metastatic pancreatic cancer who harbor somatic mutations. 

Dr. Richards on Using PARP Inhibitors in Metastatic Pancreatic Cancer

Donald A. Richards, MD, PhD, medical oncologist, Texas Oncology, discusses the design and findings of the phase III POLO trial in patients with pancreatic cancer.

In the trial, investigators evaluated the use of olaparib (Lynparza) as maintenance therapy in patients with advanced pancreatic cancer who harbored a 

 mutation. After screening 3315 patients with pancreatic cancer, investigators identified 247 patients with germline mutations, says Richards. In order to be eligible for enrollment, patients had to have received 4 months of platinum-based chemotherapy, and have stable disease or be in partial remission.

Patients were randomized 3:2 to receive oral olaparib tablets at 300 mg twice daily (n = 92) versus placebo (n = 62). The primary endpoint of the study was progression-free survival (PFS). The results, which were presented at the 2019 ASCO Annual Meeting, showed a median PFS of 7.4 months and 3.8 months with olaparib and placebo, respectively, which translated to a 47% reduction in the risk of progression or death. Overall survival (OS) was a key secondary endpoint. At the time of analysis, there did not appear to be a difference between arms in terms of OS. However, these data are immature and require further follow-up, says Richards.

Dr. Richards on the Phase III POLO Trial in BRCA-Mutated Pancreatic Cancer

Donald A. Richards, MD, PhD, medical oncologist, Texas Oncology, discusses PARP inhibition in patients with pancreatic cancer.

Patients with pancreatic cancer who have 

 mutations are unable to repair double-strand breaks in the DNA. PARP inhibitors increase the number of single-strand breaks.

 mutations have the lethal mutations accumulate. A normal cell without the 

 mutation can repair itself, but the dual PARP inhibition in the DNA repair for patients with 

Donald A. Richards, MD, PhD

Articles

Dr. Richards on Genetic Testing in Metastatic Pancreatic Cancer

Dr. Richards on Secondary Endpoints of the POLO Trial in Pancreatic Cancer

Dr. Richards on Using PARP Inhibitors in Metastatic Pancreatic Cancer

Dr. Richards on the Phase III POLO Trial in BRCA-Mutated Pancreatic Cancer

Dr. Richards on PARP Inhibition in Pancreatic Cancer