by Dr. C.H. Weaver M.D. updated 6/2019
The results of a phase III trial presented on June 2 at the annual meeting of the American Society of Clinical Oncology (ASCO) show that the Lynparza (olaparib) PARP inhibitor delays cancer progression and improves survival when used to treat BRCA-mutated pancreatic cancer and appears to represent a new treatment option for this hard to treat cancer. (1-4) Results are being published simultaneously in the New England Journal of Medicine.
The US Food and Drug Administration (FDA) had recently granted orphan drug designation for Lynparza based on the preliminary results of the POLO clinical trial.
First Precision Cancer Medicine Approved for Treatment of Pancreatic Cancer
The "POLO" clinical trial, was conducted at 119 sites in 12 countries. It enrolled 151 patients with metastatic pancreatic cancer who tested positive for a BRCA mutation and whose tumors had been responding to treatment with a platinum-based chemotherapy for at least four months. Patients were randomized in a double-blind fashion. (This means neither the investigators nor the patients knew which group they belonged to.) Groups were assigned to either Lynparza or a placebo. The study monitored progression-free survival, which is the amount of time a person’s cancer either shrinks or doesn’t get worse.
When the study data were unblinded, the investigators found that progression-free survival was significantly longer in the Lynparza treated patients. It took about twice as long for cancer to progress in people on Lynparza compared with those on a placebo After two years, the cancer in 22.1% of the people taking Lynparza had not progressed versus 9.6% of those taking a placebo.
About BRCA Mutated Pancreatic Cancer
Pancreatic cancer has the worst survival rate of the most common cancers and less than seven percent of patients survive more than five years after diagnosis. Germline BRCA-mutated pancreatic cancer accounts for ~7% of all pancreatic cancers.(2)
BRCA1 and BRCA2 are human genes that produce proteins responsible for repairing damaged DNA. When either of these genes is mutated, or altered DNA damage may not be repaired properly, and the cells are more likely to develop additional genetic alterations that can lead to cancer.
Compared with chemotherapy, PARP inhibitors are better tolerated over the long term. The most common side effects of PARP inhibitors are anemia and fatigue. Common side effects of platinum-based chemotherapy include neuropathy (weakness, numbness, or pain in the hands and feet), nausea, and anemia. Lynparza is a pill, whereas chemotherapy is given by IV.
About the POLO Clinical Trial
The POLO clinical trial evaluated the effectiveness of Lynparza tablets as 1st-line maintenance therapy in 154 patients with gBRCAm metastatic pancreatic cancer whose disease had not progressed following treatment with 1st-line platinum-based chemotherapy. Patients were treated with Lynparza or placebo and directly compared and the initial trial results report that Lynparza significantly delays cancer progression.
Lynparza is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated for the treatment of selected patients with ovarian, fallopian tube, or primary peritoneal cancer. The PARP enzyme plays a role in DNA repair, including the repair of DNA damage from chemotherapy. Precision cancer medicines that target and inhibit this enzyme may contribute to cancer cell death and increased sensitivity to chemotherapy and are called PARP inhibitors. By blocking this enzyme, DNA inside the cancerous cells is less likely to be repaired, leading to cell death and possibly a slow-down or stoppage of tumor growth.
The use of Lynparza in pancreatic cancer is being assessed in the ongoing Phase III POLO trial, which is testing Lynparza as maintenance monotherapy vs placebo in patients with germline BRCA-mutated metastatic pancreatic cancer whose disease has not progressed following 1st-line platinum-based chemotherapy. Results from the POLO trial are expected in the first half of 2019.
- World Cancer Research Fund International. Pancreatic cancer statistics. Accessed February 2019 from <a href="https://www.wcrf.org/dietandcancer/cancer-trends/pancreatic-cancer-statistics">https://www.wcrf.org/dietandcancer/cancer-trends/pancreatic-cancer-statistics</a>
- Holter S et al. Journal of Clinical Oncology. 2015; 33; 3124-3129.
- Pancreatic Cancer Action. Facts and statistics. Accessed February 2019 from <a href="https://pancreaticcanceraction.org/about-pancreatic-cancer/medical-professionals/stats-facts/facts-and-statistics/">https://pancreaticcanceraction.org/about-pancreatic-cancer/medical-professionals/stats-facts/facts-and-statistics/</a>