José Baselga, MD, PhD
Frontline maintenance therapy with olaparib (Lynparza) significantly reduced the risk of disease progression or death versus placebo in patients with germline BRCA
m) metastatic adenocarcinoma of the pancreas, according to findings from the phase III POLO trial announced by AstraZeneca and Merck (MSD), the codevelopers of the PARP inhibitor.1
Beyond the improvement in progression-free survival (PFS), the companies also reported that there were no new safety signals with olaparib. AstraZeneca and Merck plan to report the specific data from the trial at a future medical meeting.
“This is the first positive phase III trial of any PARP inhibitor in germline BRCA
-mutated metastatic pancreatic cancer, a devastating disease with critical unmet need. Most patients are diagnosed late, leaving them with a poor prognosis and very limited treatment options. Based on POLO, Lynparza becomes the first PARP inhibitor to demonstrate positive phase III results beyond ovarian cancer and breast cancer,” José Baselga, MD, PhD, executive vice president, Research and Development, Oncology, AstraZeneca, said in a press release.
In the POLO study, 154 patients with gBRCA
m-positive metastatic pancreatic cancer were randomized 3:2 to receive oral olaparib tablets at 300 mg twice daily as maintenance therapy versus placebo, also twice daily. Randomization occurred within 6 weeks following last chemotherapy dose and olaparib/placebo treatment began within 4 to 8 weeks of the last chemotherapy dose. Following randomization, patients had weekly clinical visits for the first 4 weeks of treatment, then every 4 weeks while on study treatment.
Treatment continued until objective radiological disease progression. Following progression, patients were followed for second progression every 8 weeks, and then for survival until final analysis.
Eligible patients were previously treated for metastatic disease and had not progressed following completion of at least 16 weeks of frontline platinum-based chemotherapy. Additionally, patients had to have a known deleterious or suspected deleterious germline BRCA
mutation. Those who were previously treated with a PARP inhibitor were excluded.
The primary endpoint was PFS. Secondary endpoints were overall survival, time from randomization to second progression or death, objective response rate, disease control rate, safety, and tolerability.
“Trials like POLO demonstrate the shared commitment of MSD and AstraZeneca to assess treatments for difficult-to-treat cancers. The clinically meaningful results of this trial potentially support the value of testing for germline BRCA
mutations in patients with metastatic pancreatic cancer,” Roy Baynes, senior vice president and head of Global Clinical Development, chief medical officer, MSD Research Laboratories, said in a press release.
In October 2018, the FDA granted olaparib an orphan drug designation for the treatment of patients with pancreatic cancer. This designation status is issued to medicines intended for the treatment, diagnosis, or prevention of rare diseases or disorders that affect fewer than 200,000 people in the United States. Pancreatic cancer accounts for approximately 3% of all US cancers and 5-year survival rates remain at 8.5%, AstraZeneca reported in a news release.2
Olaparib currently has FDA-approved indications in breast cancer and ovarian cancer.
- AstraZeneca. Lynparza significantly delayed disease progression as 1st-line maintenance treatment in germline BRCA-mutated metastatic pancreatic cancer. Published February 26, 2019. Access February 26, 2019. https://bit.ly/2BSBlHE.
- AstraZeneca. US FDA grants Lynparza orphan drug designation for pancreatic cancer. Published October 16, 2018. Accessed February 26, 2019. https://bit.ly/2pYa7c8.