People with a genetic mutation linked to cancer risk
Pancreatic cancer survivors
Special populations: BRCA mutation carriers with pancreatic cancer
Note: On 12/27/19, the FDA approved olaparib for treatment of pancreatic cancer in people with a BRCA mutation based on the results of the POLO study.
The POLO clinical trial looks at whether the PARP inhibitor olaparib improves outcomes for those with metastatic pancreatic cancer after platinum-based chemotherapy. (7/3/19) Based on these results
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whether olaparib prolongs disease-free survival for patients with metastatic pancreatic cancer who have BRCA mutations
People with metastatic pancreatic cancer have poor survival rates and do not respond well to current treatments. Olaparib is a type of drug known as a PARP inhibitors that has received FDA approval to treat advanced breast and ovarian cancers in people with BRCA mutations. This clinical trial looked at whether the PARP inhibitor olaparib can improve outcomes for men and women with pancreatic cancer after platinum-based chemotherapy.
If you or a relative have metastatic pancreatic cancer, you may want to consider BRCA testing, because testing positive for a BRCA mutation may change treatment options.
Note: This information has been updated. On December 27, 2019 the FDA approved the PARP inhibitor olaparib (Lynparza) as a maintenance therapy for patients with pancreatic cancer and a known or suspected BRCA mutation whose disease has not progressed after completing chemotherapy.
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The National Comprehensive Cancer Network (NCCN) develops guidelines for experts on best practice within cancer care. Newer NCCN guideline recommendations for metastatic pancreatic cancer include that clinicians consider
For metastatic pancreatic cancer patients, modified FOLFIRINOX (fluorouracil [5-FU], leucovorin, irinotecan, oxaliplatin) or gemcitabine/nab-paclitaxel chemotherapy is recommended as a first treatment approach with surgery.
For patients with BRCA1/2 PALB2 mutations, gemcitabine/cisplatin is recommended as a first treatment approach with surgery. Recent recommendtion updates suggest considering olaparib for mainenance therapy for some patients with BRCA mutations and no progression platinum-based chemotherapy.
NCCN suggests tumor testing for patients with metastatic pancreatic cancer for a biomarker known as Microsatellite Instability (MSI). The immunoncology agent pembrolizumab (Keytruda) has been approved to treat patients with advanced cancer who test MSI high.
The following clinical trials are currently recruiting pancreatic cancer patients:
Pancreatic cancer has already metastasized in over half of people who are diagnosed . Metastatic pancreatic cancer does not respond well to current standard of care treatment, which is surgery followed by radiation or chemotherapy, often modified with FOLFIRINOX (leucovorin/5-FU/irinotecan/oxaliplatin). On average, standard chemotherapy care produces progression-free survival of 6 months. About 9% of patients survive 5 years after initial diagnosis. Given the poor response of metastatic pancreatic cancer, researchers have been exploring treatments that can improve outcomes.
In people with BRCA mutation who have breast or ovarian cancer, PARP inhibitors, in particular olaparib (also called Lynparza), can be an effective first-line and maintenance treatments that prolong progression-free survival. The POLO trial (Pancreas Cancer Olaparib Ongoing) was designed to test whether olaparib is useful in treating metastatic pancreatic cancer after platinum-based chemotherapy. Between 5 and 10% of patients with pancreatic cancer have an inherited BRCA gene mutation.
Whether olaparib as a maintenance treatment after platinum-based chemotherapy improved progression-free survival of metastatic pancreatic cancer patients who had an inherited BRCA mutation.
Patients were eligible for this clinical trial if they had an inherited BRCA1 or BRCA2 mutation and had confirmed metastatic pancreatic cancer that did not progress during their initial platinum-based chemotherapy.
This study involved 3,315 confirmed pancreatic cancer patients from 119 medical sites in 12 countries who were screened for BRCA mutations.
Of the 3,315 patients, 247 (7.5%) had an inherited BRCA mutation. Patients whose disease progressed while on chemotherapy during the evaluation process were ineligible for the clinical trial.
About two-thirds of the 154 eligible male and female participants had a mutation in BRCA2 and one-third had a mutation in BRCA1. Average age was 57 years.
Participants were randomly assigned to receive olaparib (90 of 92) or placebo (61 of 62). One participant assigned to olaparib and one assigned to placebo did not meet eligibility at the start of the trial (due to disease progression), and one assigned to olaparib withdrew prior to the start of the trial.
This clinical trial was a randomized, double-blind, placebo-controlled phase 3 trial.
Participants were randomly assigned to take either olaparib or placebo; they were unaware during the trial which they received.
Participants receiving olaparib took 300 mg tablets twice a day. Those receiving placebo had look-alike tablets but without olaparib. Treatment with both pills continued until the participant's cancer progressed, they had unacceptable toxic side effects or the participant died.
The primary end point of this trial was progression-free survival. Participants were evaluated for disease progression by MRI or CT imaging every 8 weeks for 40 weeks and then every 12 weeks until disease progression was observed. The imaging data was evaluated by an independent reviewer who did not know whether participants were receiving olaparib or placebo.
Secondary end points included health-related quality of life, overall survival and objective response rate. Participants filled out a questionnaire every 4 weeks to evaluate health-related quality of life.
This clinical trial was funded by AstraZeneca, a division of Merck, and others and run under FDA oversight as POLO ClinicalTrials.gov (NCT02184195).
The main finding of this clinical trial was that participants taking olaparib experienced prolonged progression-free survival that was twice as long as those on placebo.
The data on overall survival was not fully complete at the time of this publication (46% of patients had died).
The objective response rate (ORR)—whether the cancer decreased in size during the trial was evaluated by blinded, independent reviewers.
Quality of life evaluations were similar in both groups:
Adverse events including toxic side effects were more common among participants taking olaparib than among those taking placebo:
This trial had several limitations.
Participants did not include anyone who had cancer that grew during their first platinum-based chemotherapy treatment or anyone who had extended chemotherapy. For this reason, the patients in this trial may not completely represent all of those that would be treated with this drug.
Participants were screened for BRCA mutations. Other mutations that may affect metastatic pancreatic cancer were not evaluated to determine whether olaparib might be useful as a treatment.
Initial results showed that overall survival was not improved among those taking olaparib compared to those taking placebo. Patients in the placebo group who had cancer that grew during the trial sometimes took other drugs. Changes in which therapy some participants received may affect their survival: 9 patients who were in the placebo group (15%) took a PARP inhibitor after disease progression during the trial.
This clinical trial shows that olaparib may improve progression-free survival for patients with metastatic pancreatic cancer that had not progressed on platinum-based chemotherapy.
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