Lynparza significantly delays disease progression as first-line treatment in prostate cancer

Lynparza and other inhibitors of PARP have become established in the treatment of ovarian cancer over the past few years. Last year, they entered the prostate cancer setting with the approval of Clovis’ Rubraca (rucaparib) and AstraZeneca and Merck/MSD’s Lynparza (olaparib).

Now, high-level results from the PROpel phase 3 trial in first-line metastatic castration-resistant prostate cancer (mCRPC) show that Lynparza in combination with abiraterone significantly delayed disease progression.

The data monitoring committee concluded that the trial met the primary endpoint of radiographic progression-free survival (rPFS) versus standard-of-care abiraterone in men who had not received treatment with new hormonal agents or chemotherapy.

The PROpel trial also “showed a trend” towards improved overall survival but AstraZeneca said the data were “still immature” and the trial will assess OS as a key secondary endpoint.

Prostate cancer is the second-most common cancer in men and five-year survival remains low for men with mCRPC in spite of new treatments.

“These exciting results demonstrate the potential for Lynparza with abiraterone to become a new 1st-line option for patients regardless of their biomarker status and reach a broad population of patients living with this aggressive disease,” said Susan Galbraith, head of oncology R&D at AstraZeneca. “We look forward to discussing the results with global health authorities as soon as possible.”

Olaparib blocks poly ADP ribose polymerase (PARP), an enzyme that repairs DNA damage, thus allowing cell death in cancer cells. It is being tested in a range of PARP-dependent tumour types.

Lynparza is approved in a number of countries in a range of indications, mostly related to ovarian cancer, although it is also approved for forms of advanced breast and pancreatic cancer in several countries.

The drug is being jointly developed and commercialised by AstraZeneca and Merck/MSD, and has been used to treat over 40,000 patients worldwide. It is also the focus of “the broadest and most advanced clinical trial development programme of any PARP inhibitor”, according to AstraZeneca and Merck.

The two companies have working together in oncology since 2017, with efforts focused largely on Lynparza and Koselugo (selumetinib), a mitogen-activated protein kinase (MEK) inhibitor, for multiple cancer types.