Olaparib significantly delayed disease progression as first-line maintenance treatment in germline BRCA-mutated metastatic pancreatic cancer

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Results from the Phase III POLO trial showed a statistically significant and clinically meaningful improvement in progression-free survival (PFS) with olaparib vs. placebo.

The safety and tolerability profile of olaparib was consistent with previous trials.

POLO is a randomised, double-blinded, placebo-controlled trial exploring the efficacy of olaparib tablets as first-line maintenance monotherapy in patients with germline BRCA-mutated (gBRCAm) metastatic adenocarcinoma of the pancreas (pancreatic cancer) whose disease has not progressed on platinum-based chemotherapy.

José Baselga, Executive Vice President, Research and Development, Oncology, said: “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. The results of POLO provide further evidence of the clinical benefit of olaparib across a variety of BRCA-mutated tumour types. We will discuss these results with global health authorities as soon as possible.”

Roy Baynes, Senior Vice President and Head of Global Clinical Development, Chief Medical Officer, MSD Research Laboratories, said: “Trials like POLO demonstrate the shared commitment 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.”

The POLO trial

POLO is a Phase III randomised, double-blinded, placebo-controlled, multicentre trial of olaparib tablets (300mg twice daily) as maintenance monotherapy vs. placebo.

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

Patients were randomised (3:2) to receive olaparib or placebo until disease progression.

The primary endpoint was PFS and key secondary endpoints included overall survival, time to second disease progression, overall response rate, disease control rate and health-related quality of life.

Olaparib

Olaparib is a first-in-class PARP inhibitor and the first targeted treatment to block DNA damage response in cells/tumours harbouring a deficiency in homologous recombination repair (HRR), such as mutations in BRCA1 and/or BRCA2.

Inhibition of PARP with olaparib leads to the trapping of PARP bound to DNA single-strand breaks, stalling of replication forks, their collapse and the generation of DNA double-strand breaks and cancer cell death.

Olaparib is being tested in a range of PARP-dependent tumour types with defects and dependencies in the DDR.

Olaparib is approved for multiple indications in advanced ovarian cancer and metastatic breast cancer and has been used in over 20,000 patients worldwide.

Olaparib has the broadest and most advanced clinical trial development programme of any PARP inhibitor, and researchers are working to understand how it may affect multiple PARP-dependent tumours as a monotherapy and in combination across multiple cancer types.

Pancreatic cancer

Pancreatic cancer is the 12th most common cancer worldwide, with 1 with 466,000 new cases in 2018 alone.

Germline BRCA-mutated pancreatic cancer accounts for five to seven percent of all cases globally.

With the worst survival rate of the most common cancers, it is the fourth leading cause of cancer death and less than seven percent of patients survive more than five years after diagnosis.

Early diagnosis of pancreatic cancer is difficult, as often there are no symptoms until it is too late.

Around 80 percent of patients are diagnosed at the metastatic stage.

BRCA mutations

BRCA1 and BRCA2 are human genes that produce proteins responsible for repairing damaged DNA and play an important role in maintaining the genetic stability of cells.

When either of these genes is mutated or altered, such that its protein product either is not made or does not function correctly, DNA damage may not be repaired properly and cells become unstable.

As a result, cells are more likely to develop additional genetic alterations that can lead to cancer.


Source: AstraZeneca

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The ONA Editor curates oncology news, views and reviews from Australia and around the world for our readers. In aggregated content, original sources will be acknowledged in the article footer.

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