Study: Results from the POLO trial: Olaparib may delay cancer progression in metastatic pancreatic cancer patients with BRCA mutations.
|At a glance||Questions for your doctor|
This study is about:
whether olaparib prolongs disease-free survival for patients with pancreatic cancer who have mutations
Why is this study important?
People with 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 approval to treat advanced breast and ovarian cancers in people with mutations. This clinical trial looked at whether the olaparib can improve outcomes for men and women with pancreatic cancer after platinum-based chemotherapy.
- Participants taking olaparib had progression-free survival that was twice as long as those on (7.4 months among the olaparib group and 3.8 months among the group).
- At the trial’s interim evaluation point, there was no difference in the overall survival among the olaparib and groups.
- Cancer decreased in size during the trial in the 23% of the olaparib group participants and 12% of the group participants.
- Two patients from the olaparib group had a complete response at the time of publication.
- There was no difference in health-related quality of life between participants taking olaparib and those taking .
- Toxic side effects were more common among participants taking olaparib (40%) than among those taking (23%).
What does this mean for me?
If you or a relative have pancreatic cancer, you may want to consider testing, because testing positive for a mutation may change treatment options.
Note: This information has been updated. On December 27, 2019 the approved the olaparib (Lynparza) as a for patients with pancreatic cancer and a known or suspected mutation whose disease has not progressed after completing chemotherapy.
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Goaln T, Hammel P, Reni M, et al. “Maintenance Olaparib for Germline BRCA-Mutated Pancreatic Cancer.” New England Journal of Medicine. June 2, 2019. DOI: 10.1056/NEJMoa1903387
Pihlak R, Valle JW, McNamara MG. "Germline mutations in pancreatic cancer and potential new therapeutic options." Oncotarget. 2017 Sep 22; 8(42): 73240–73257.
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This article is relevant for:
People diagnosed with pancreatic cancer who have a BRCA mutation
This article is also relevant for:
People with a genetic mutation linked to cancer risk
Pancreatic cancer survivors
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Pancreatic cancer has already metastasized in over half of people who are diagnosed . 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 pancreatic cancer, researchers have been exploring treatments that can improve outcomes.
In people with 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 pancreatic cancer after platinum-based chemotherapy. Between 5 and 10% of patients with pancreatic cancer have an inherited gene mutation.
Researchers of this study wanted to know:
Whether olaparib as a maintenance treatment after platinum-based chemotherapy improved progression-free survival of pancreatic cancer patients who had an inherited mutation.
Populations looked at in this study:
Patients were eligible for this clinical trial if they had an inherited or mutation and had confirmed 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 mutations.
Of the 3,315 patients, 247 (7.5%) had an inherited 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 and one-third had a mutation in . Average age was 57 years.
Participants were randomly assigned to receive olaparib (90 of 92) or (61 of 62). One participant assigned to olaparib and one assigned to 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 , double-blind, 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 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 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 .
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 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 .
- Participants taking olaparib had 7.4 months on average before disease progression occurred.
- Participants taking had 3.8 months on average before disease progression occurred.
The data on overall survival was not fully complete at the time of this publication (46% of patients had died).
- At this interim evaluation point, there was no difference in the overall survival among the olaparib and groups (18.9 months survival with olaparib and 18.1 months survival with ).
The objective response rate (ORR)—whether the cancer decreased in size during the trial was evaluated by blinded, independent reviewers.
- 18 of 78 patients (23%) in the olaparib group had decreased tumor size.
- 6 of 52 patients in the group (12%) had decreased tumor size.
- Two patients from the olaparib group had a complete response. No cancer was observable in these two patients at the time of publication.
Quality of life evaluations were similar in both groups:
- There was no difference in health-related quality of life between participants taking olaparib and those taking .
Adverse events including toxic side effects were more common among participants taking olaparib than among those taking placebo:
- 40% of participants taking olaparib had severe adverse events.
- 23% of participants taking had severe adverse events.
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 mutations. Other mutations that may affect 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 . Patients in the 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 group (15%) took a after disease progression during the trial.
This clinical trial shows that olaparib may improve progression-free survival for patients with pancreatic cancer that had not progressed on platinum-based 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 pancreatic cancer include that clinicians consider
- genetic testing for all patients with pancreatic cancer.
- tumor testing in patients with disease.
- combination chemotherapy with modified FOLFIRINOX (leucovorin/5-FU/irinotecan/oxaliplatin) for patients who are able to tolerate it.
For 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 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 mutations and no progression platinum-based chemotherapy.
NCCN suggests tumor testing for patients with pancreatic cancer for a known as (MSI). The immunoncology agent pembrolizumab (Keytruda) has been approved to treat patients with advanced cancer who test MSI high.
The National Comprehensive Cancer Network (NCCN) recommends the following for people diagnosed with pancreatic cancer:
- Receive treatment from a (MDT): Treatment decisions should involve an MDT that includes a team of doctors, healthcare workers, genetic counselors and mental health professionals who have expertise and experience with treating and addressing issues related to your type of cancer. MDTs are more likely to be found or affiliated with cancer centers that have experience in treating pancreatic cancer.
- Have tumors staged via imaging tests: is needed to plan and monitor your treatment. Imaging tests (e.g., tomography scans) are used to pancreatic cancer. The tests determine whether the tumor can be removed with surgery (resectable) if cancer has spread to nearby organs or (locally advanced) or has spread to other parts of the body (metastasized).
- Discuss with your healthcare team whether they recommend chemotherapy before and/or after your surgery.
- Have genetic testing, using a comprehensive gene panel for (this applies to anyone who is diagnosed with pancreatic cancer).
- Genetic testing results may be used in making treatment decisions.
- Have tumor testing (for people with locally advanced or pancreatic cancer).
- Tumor testing results can also be used in making treatment decisions.
- Keep a copy of all test results (online patient portals are a great way to access test results). This will come in handy during a second opinion, if necessary.
- How do I get genetic testing for a mutations?
- Does carrying a mutation in or another gene change your treatment recommendations for me?
- Should I have testing?
- Which treatment is the best for me?
- Will my insurance pay for Lynparza to treat my pancreatic cancer?
- Is there a clinical trial that I can join?
The following are studies enrolling people diagnosed with pancreatic cancer:
- NCT04548752: Adding Pembrolizumab to Olaparib to Treat Pancreatic Cancer in People with an Inherited Mutation. This study is researching whether adding the drug Pembrolizumab (Keytruda) to the Olaparib (Lynparza) works better than olaparib alone for treating pancreatic cancer in people with an inherited or mutation.
- NCT05252390: NUV-868 Alone and in Combination With PARP Inhibitors in Patients With Advanced .
This study will test how safe and effective the experimental drug NUV-868 is by itself and in combination with a in people with advanced .
- NCT04229004: Precision Promise Platform Trial for Pancreatic Cancer. This study tests different treatments for pancreatic cancer.
- NCT04267939: ATR Inhibitor BAY 1895344 Plus Phase 1b Study in Advanced and Ovarian Cancer. This study will look at how well advanced respond to treatment with the BAY1895344 combined with the niraparib.
- NCT04493060: Treating Pancreatic Cancer with an Inherited or Tumor BRCA1/2 or Mutation with and Dostarlimab. This study looks at how well the and the drug dostarlimab work together in treating patients with pancreatic cancer, who have an inherited or tumor mutation in , , , , , or .
- NCT03337087: Treating Pancreatic, Colorectal, Gastroesophageal, or Biliary Cancer with Chemotherapy and This study will look at how the works with chemotherapy to treat people with pancreatic, colorectal, gastroesophageal or biliary cancer. The study will measure the best dose and look at the side effects of this combination of drugs.
- NCT04150042: A Study of Melphalan, BCNU, Vitamin B12b, Vitamin C and Stem Cell Infusion in People with Advanced Pancreatic Cancer and Mutations. This study will look at whether combining melphalan, BCNU, vitamin B12b and vitamin C, followed by autologous (self) bone marrow stem cell infusion, is safe and effective for treating people with advanced pancreatic cancer who have a or gene mutation.
- NCT04666740: Pembrolizumab and Olaparib for Pancreatic Cancer with or Exceptional Response to Platinum Chemotherapy. This is a study for people diagnosed with pancreatic cancer with a tumor test result called HRD-positive, or whose disease has responded well to first-line or second-line platinum therapy. The study will look at whether combining the drug pembrolizumab and the olaparib is a more effective treatment for this cancer than olaparib alone.
- NCT04858334: Olaparib or in Patients with Surgically Removed Pancreatic Cancer who have a , or Mutation (APOLLO). The purpose of EA2192 / APOLLO is to compare the usual approach (observation) to treatment for one year with olaparib, in patients with a , or mutation.
- NCT04657068: Treatment with ATR Inhibitor for Advanced or Solid Tumors. This study will look at how well a new oral known as an ATR inhibitor works on advanced or solid tumors with mutations in genes linked to damage repair. The study will look at the response to treatment with the drug ART0380 in combination with the chemotherapy agent, gemcitabine.
Other clinical trials for people with pancreatic cancer can be found here.
The following are studies looking at treatment for people with advanced .
- NCT05252390: NUV-868 Alone and in Combination With PARP Inhibitors in Patients With Advanced . This study will test how safe and effective the experimental drug NUV-868 is by itself and in combination with a in people with advanced . This study is open to people whose cancer stopped responding or progressed on PARP inhibitors.
- NCT05169437: () in patients with inherited or tumor mutations in advanced (PAVO). PAVO is a Phase II study investigating if the study drug, a called , is safe and effective for certain people who have been diagnosed with an advanced solid tumor with either an inherited or tumor mutation.
- NCT02264678: Ascending Doses of Ceralasertib in Combination With Chemotherapy and/or Novel Anti Cancer Agents. This is a study of ceralasertib administered orally in combination with chemotherapy regimens and/or novel anti-cancer agents, to patients with advanced cancer. The study is enrolling people with inherited mutations including , , , , and people with tumors that are HRD-positive.
- NCT04644068: Study of AZD5305 as Monotherapy and in Combination With Anti-cancer Agents in Patients With Advanced Solid Malignancies (PETRA). This research is designed to learn if treatment with a new , AZD5305, alone, or in combination with anti-cancer agents is safe, tolerable, and has anti-cancer activity in patients with advanced . The study is open to people who have previously been treated with PARP inhibitors.
- NCT04267939: ATR Inhibitor Plus Study in Advanced and Ovarian Cancer. This study will look at how well how well people with advanced respond to treatment with the BAY1895344 in combination with the . This study is open to people with inherited mutations in , , and others. Contact the study coordinator for information about eligilibity for people with mutations in other genes.
- NCT04657068: Treatment with ATR Inhibitor for Advanced or Solid Tumors. This study will look at how well a new oral known as an ATR inhibitor works on advanced or with mutations in genes linked to damage repair. This study is open to people who have an inherited or acquired or mutation or people with tumors that are HRD-positive. This study is open to people whose cancer stopped responding or progressed on PARP inhibitors.
The following organizations offer peer support services for people with or at high risk for pancreatic cancer:
- FORCE peer support
- Our Message Boards allow people to connect with others who share their situation. Once registered, you can post on the Diagnosed With Cancer board to connect with other people who have been diagnosed.
- Peer Navigation Program will match you with a volunteer who shares your mutation and situation.
- Private Facebook Group
- Virtual and in-person support meetings
- Join a Zoom community group meeting.
- American Sign Language
- People of Color
- Let's Win PC
- The Healing NET Foundation is a nonprofit organization for people with neuroendocrine cancers.
- The Neuroendocrine Cancer Awareness Network (NCAN) is a non-profit organization dedicated to raising awareness of neuroendocrine cancer and providing support for caregivers and people with NETs.
Who covered this study?
https://www.biopharmadive.com/news/asco-19-lynparza-pancreatic-cancer-progression-astrazeneca/555982/ This article rates 5.0 out of 5 stars
POLO Will Change Practice in Pancreatic Cancer This article rates 4.0 out of 5 stars
Pancreatic cancer therapy sheds light on the disease's ties to BRCA mutation This article rates 3.0 out of 5 stars
AstraZeneca's Lynparza Slows Spread of Rare Pancreatic Cancer This article rates 2.0 out of 5 stars