AZ/Merck & Co’s Lynparza delays spread of pancreatic cancer

AstraZeneca and Merck & Co’s Lynparza could offer a new option for certain patients with pancreatic cancer after a trial showed it slowed progression of the disease.

Lynparza (olaparib) is a poly (ADP-ribose) polymerase, or PARP inhibitor class drug and is already established as a therapy for ovarian and breast cancer with BRCA mutations.

The results add to the evidence that Lynparza and perhaps other PARP class drugs could work in other types of cancer that have the mutation, after approvals in ovarian and breast cancer.

They are also significant as pancreatic cancer is difficult to treat, only causing symptoms when it has become well established, meaning survival rates are low.

Phase 3 results from the POLO trial show that the drug could be a maintenance therapy option in patients with germline BRCA-mutated (gBRCAm) metastatic adenocarcinoma of the pancreas, whose disease has not progressed on platinum-based chemotherapy.

Results showed a statistically significant and clinically meaningful improvement in progression-free survival with Lynparza compared with placebo, AZ said.

Safety and tolerability of Lynparza was consistent with previous trials, the companies said.

POLO is a phase 3 randomised, double-blinded, placebo-controlled, multicentre trial of Lynparza tablets (300 mg twice daily) as maintenance monotherapy versus placebo.

The trial randomised 154 patients with gBRCAm metastatic pancreatic cancer whose disease had not progressed in first-line platinum-based chemotherapy.

Patients were randomised (3:2) to receive Lynparza or placebo until disease progression. The primary endpoint was progression-free survival and secondary endpoints included overall survival, time to second disease progression, overall response rate, disease control rate and health-related quality of life.

Lynparza works by blocking response to DNA damage in cancer cells with mutations such as BRCA, which cause deficiency in the homologous recombination repair (HRR) system in cells.

By inhibiting the protein known as PARP, Lynparza causes a chain reaction that leads to a generation of breaks in the cancer cell’s DNA and eventually its death.

Lynparza is being tested in other cancers, including gastric and prostate cancer.

There are other PARP drugs on the market too: GlaxoSmithKline/Tesaro’s Zejula (niraparib) is approved in ovarian cancer, and Clovis’ Rubraca (rucaparib) is also approved in ovarian cancer and has shown promise in prostate and pancreatic cancer.

Originally developed by AZ, Lynparza is now being jointly developed and marketed with US-based Merck & Co under a partnership signed in 2017.

The companies are also co-developing the MEK inhibitor selumetinib and are looking for new combination therapies.

Independently, the companies will develop Lynparza and selumetinib in combination with their respective PD-L1 and PD-1 medicines.

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