Pancreas Cancer: AIFA Approves Olaparib for BRCA-Mutated Patients

A significant advancement has been made in the treatment of one of the most aggressive and difficult-to-cure cancers: metastatic pancreatic adenocarcinoma. The Italian Medicines Agency (AIFA) has approved reimbursement for olaparib, a targeted therapy and the first-in-class PARP inhibitor, for maintenance treatment of patients with metastatic pancreatic adenocarcinoma and BRCA1/2 mutations who have not experienced disease progression after at least 16 weeks of first-line platinum-based chemotherapy.

A Breakthrough for a Subset of Patients

In 2024, an estimated 13,585 new cases of pancreatic cancer were reported in Italy, with approximately 7% presenting with BRCA1/2 gene mutations. For this specific patient population, the POLO study demonstrated a 47% reduction in the risk of disease progression with olaparib.

The POLO Study

“Metastatic pancreatic adenocarcinoma is one of the cancers with the most unfavorable prognosis, characterized by late diagnosis, an extremely rapid clinical course, and a significant impact on patients’ quality of life,” explains Michele Reni, Director of Medical Oncology at the IRCCS San Raffaele Hospital in Milan and Associate Professor of Oncology at the Vita-Salute San Raffaele University. “The international phase III POLO study, published in the New England Journal of Medicine, involved 154 patients with pancreatic adenocarcinoma with germline mutations in the BRCA1/2 genes, who had received at least 16 weeks of first-line chemotherapy with platinum derivatives without disease progression. Progression-free survival was nearly doubled with olaparib, reaching 7.4 months compared to 3.8 months with placebo. Here’s a statistically significant result; to date, no maintenance treatment for pancreatic cancer has improved progression-free survival.”

three-year survival rates were 33.9% for patients receiving olaparib compared to 17.8% with placebo.

Did You Know? The POLO study is the first to demonstrate a benefit with a molecularly targeted drug in pancreatic cancer based on a genetic mutation.

BRCA Mutation Testing

“POLO is the first study to establish a benefit with a targeted drug in pancreatic carcinoma based on a genetic mutation,” continues Reni. “This opens a path already successfully traveled in other cancers, where patients receive therapies based on mutations in the genetic-molecular profile.” testing for BRCA mutations is crucial for all patients at the time of pancreatic cancer diagnosis. This testing is not always performed in Italy, as highlighted by a report indicating disparities in access to genetic testing for hereditary cancers.

The BRCA gene mutations, famously linked to actress Angelina Jolie’s decision to undergo preventative mastectomy and removal of her fallopian tubes and ovaries, are not solely a “women’s issue” as they have been associated with an increased risk of developing cancers of the breast, ovary, prostate, and pancreas. Testing is also important for family members, as a positive BRCA test result in a patient with pancreatic cancer allows for the identification of at-risk relatives who may benefit from preventative programmes.

Reduced Risk of Mortality

Pancreatic cancer is among the most difficult to treat and diagnose. There are no screening tests available, and the disease typically manifests with late-stage symptoms. Only 20% of cases are diagnosed in the early stages, when surgery may still offer a cure. Despite improvements in chemotherapy and supportive care, the prognosis for pancreatic adenocarcinoma remains among the worst of all solid tumors.

“The management of advanced pancreatic adenocarcinoma has been based for decades on chemotherapy, with a significant toxicity burden for prolonged treatments and relatively few options for patients who no longer respond to first-line therapy,” adds Michele Milella, Director of Oncology at the Integrated University Hospital of Verona. “scientific research has focused on identifying the molecular targets underlying the disease, such as the BRCA genes, which increase the risk of developing not only breast, ovarian, and prostate cancers, but also pancreatic cancer.”

Data from an independent Italian “real world” study, published in Cancer Medicine, supported the approval of olaparib reimbursement. The study involved 23 oncology departments across Italy and included 114 patients. The study evaluated whether the use of olaparib, both as maintenance therapy after first-line chemotherapy and in later lines of treatment, was associated with a significant and clinically relevant prolongation of overall survival in patients with metastatic pancreatic adenocarcinoma carrying BRCA1/2 mutations. Patients who received olaparib in any line of treatment, including maintenance therapy, experienced a 43% reduction in the risk of death.

Expert Insight: The Italian “real world” study provides crucial evidence supporting the value of olaparib in clinical practice, reinforcing the findings of the initial POLO study and highlighting the importance of identifying patients with BRCA mutations.

Frequently Asked Questions

What type of cancer does olaparib treat?

Olaparib is approved for the maintenance treatment of patients with metastatic pancreatic adenocarcinoma and BRCA1/2 mutations who have not experienced disease progression after at least 16 weeks of first-line platinum-based chemotherapy.

What percentage of pancreatic cancer patients have BRCA mutations?

Approximately 7% of pancreatic cancer patients in Italy present with BRCA1/2 gene mutations.

What was the key finding of the POLO study?

The POLO study demonstrated a 47% reduction in the risk of disease progression with olaparib in patients with BRCA1/2 mutations.

As research continues to unravel the genetic complexities of pancreatic cancer, will personalized treatment strategies based on individual genetic profiles become the standard of care?