According to an article in BioSpace, the FDA recently approved the PARP inhibitor Lynparza that was developed by Merck and AstraZeneca to be used as maintenance therapy for pancreatic cancer patients.
PARP (Poly ADP-ribose polymerase inhibitors) are targeted therapies that inhibit the PARP protein found in some pancreatic cancer cells.
About the Phase 3 POLO Trial
The Phase 3 POLO trial (NCT02184195) was the basis for the FDA’s approval of Lynparza (olaparib) as maintenance therapy. The trial involved 154 adult patients who were diagnosed with inherited BRCA1 or BRCA2 mutated metastatic pancreatic cancer. The two BRCA mutations are a minor subgroup of metastatic pancreatic cancer patients. Lynparza has shown significant antitumor activity in this subgroup.
Ninety-two patients were treated with Lynparza and sixty-two received a placebo. These patients were selected from a total of 3315 patients.
The criteria for eligibility included patients whose cancer had been stable for sixteen weeks and who had been treated with platinum-based chemotherapy.
The subjects were randomly selected to either receive Lynparza tablets in 300mg doses two times each day or a placebo.
Patients who received Lynparza maintenance therapy in the POLO trial saw a forty-seven percent reduction in disease progression or death.
The results were not nearly as significant with the secondary endpoint of overall survival. The interim results of overall survival showed l8.9 versus 18.1 months for Lynparza versus the placebo.
Lynparza’s tolerability and safety results from the POLO trial remained consistent with previous trials.
About Pancreatic Cancer
Pancreatic cancer is known throughout the world as a dangerous major cancer with an extremely low five-year rate of survival.
Worldwide, in eighty percent of approximately 460,000 new pancreatic cancer cases that were diagnosed in 2018, cancer had already spread (metastasized) leaving the patients with less than a one-year survival.
Lynparza Blocks DNA Damage
AstraZeneca announced that Lynparza is currently the only therapy approved to target metastasized pancreatic cancer.
Lynparza is the first therapy to block DNA damage in tumors and cells, for example, BRCA1 and BRCA2 mutations. The BRCA gene has a major role in DNA repair through a mechanism called homologous recombination repair (HRR). A mutation of the BRCA gene causes HRR deficiency and loss of the repair mechanism.
Another way to look at it is that cells use HRR for an accurate repair of harmful breaks occurring on both DNA strands. These breaks are widely known as double-strand breaks.
Other Indications for Lynparza
Lynparza was previously approved to treat breast and ovarian cancers. The drug is also under consideration for a rare type of prostate cancer as well as late-stage ovarian cancer.
In the past, patients who were in an advanced stage of pancreatic cancer were handed a poor prognosis. Lynparza is helping improve that landscape.
