Pancreatic cancer patient reviews her molecular profile report with her doctor

People with pancreatic cancer and a specific type of change – or mutation – in their DNA live longer when treated with platinum-based chemotherapy, compared to those who received the same treatment but didn’t have the same mutation type. This study is out today in Journal of Clinical Oncology (JCO) Precision Oncology and draws on data from the Pancreatic Cancer Action Network’s (PanCAN) Know Your Tumor® precision medicine service.

“Being able to define subsets of patients who should be treated a certain way, based on their tumor’s biology, underscores the value of molecular profiling to improve patient outcomes in this challenging disease,” said Lynn Matrisian, PhD, MBA, chief science officer at PanCAN and a co-author of the study. “These are the types of results we hoped to see when we launched Know Your Tumor in 2014.”

Looking at Know Your Tumor reports and follow-up patient outcomes, the study authors, led by researchers at Perthera, Inc., examined data on 820 pancreatic cancer patients who either had advanced disease or who had their tumors partially or completely removed by surgery. They then looked at whether the study participants had a specific type of mutation that impaired a DNA repair process known as homologous recombination (HR).

A person’s DNA gets damaged daily, which is why the cell is designed to repair errors in DNA through many ways, including HR. But when some genes, like the BRCA genes (BRCA1 and BRCA2), become mutated, they can no longer repair DNA by HR. Mutations in other genes can impair HR also, including PALB2, ATM, ATR, ATRX, BAP1, BARD1, BRIP1, CHEK1/2 and several others.

When HR is not functioning, certain conditions may develop, like cancer.

The patients evaluated in the study could have been born with mutations in HR genes (germline mutations) or could have mutations present only in their tumor tissue (somatic mutations). PanCAN’s Know Your Tumor is able to test patients’ tumor tissue and saliva to identify both types of mutations.

For patients with metastatic disease, those with HR-related mutations lived an average of 11 months longer when treated with platinum-based chemotherapy, as compared to patients who underwent the same treatment but didn’t have HR-related mutations.

The new study supports other research suggesting that cancers with HR-related mutations are especially vulnerable to platinum-based chemotherapy. Further, this study follows promising phase III clinical trial results showing that pancreatic cancer patients who responded to this chemotherapy type also responded well to a PARP inhibitor called Lynparza® (olaparib).

Lynparza is an FDA-approved treatment for ovarian cancer, but not yet for pancreatic cancer. Published phase III clinical trial results suggest it may have the potential to extend the good results seen by some patients undergoing platinum-based chemotherapy.

While platinum-based chemotherapy is shown to be effective for certain patients, many patients may not have the chance to benefit from this treatment type. The study authors noted that while it’s estimated that 17 to 25 percent of pancreatic cancers have HR-related mutations, about half of all patients do not receive platinum-based therapy as their first line of treatment. This highlights the importance of patients undergoing molecular profiling to identify mutations, such as those disrupting the HR pathway, or other alterations that may impact their treatment options.

“One theory in the field was that pancreatic cancer patients with HR-related mutations naturally ended up living longer than patients without such mutations,” Matrisian said. “But our study shows that’s not true. Unless they underwent platinum-based treatment, these patients did not see any survival benefit.”

Every pancreatic tumor is different. Patients who receive treatment based on their tumor’s biological characteristics have better outcomes. PanCAN strongly recommends molecular profiling to help determine best treatment options.

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