Real-time DNA sequencing in advanced pancreatic cancer can guide precision medicine treatment

A study from Dana-Farber Cancer Institute says that rapid-turnaround DNA sequencing in patients with advanced pancreatic cancer is feasible and can yield results that guide treatment decisions.

Published in Cancer Discovery, the study found that about one-third of 71 patients with metastatic pancreatic cancer had a change in their clinical care because of their genomic data, including the recommendation for some patients that family members consider genetic testing due to a potential inherited predisposition to pancreatic cancer.

"These results suggest that knowing the genetic make-up of advanced pancreatic cancer can impact patient care," said senior author Brian Wolpin, M.D., MPH, of the Gastrointestinal Cancer Center and the Hale Center for Pancreatic Cancer Research at Dana-Farber, which funded the research along with the Lustgarten Foundation.

Molecular analysis of metastatic pancreatic tumors is challenging due to the heterogeneous cellular composition of biopsy specimens and rapid progression of the disease. The Dana-Farber researchers used an integrated multi-disciplinary biopsy program, PancSeq, and whole-exome DNA sequencing to obtain results within approximately one month from the time of biopsy. Both tumor DNA and inherited DNA were sequenced for all patients.

Forty-eight percent (34/71) of patients within this cohort had cancers with at least one genomic alteration that could potentially be eligible for current clinical trials or support off-label usage of a drug approved for another indication. A total of 24% (17/71) of patients enrolled in the PancSeq study were treated with an experimental agent, either through enrollment into a clinical trial or through off-label use of an approved agent.

"One example highlighted by this work is a patient whose tumor has a somatic BRCA2 mutation with a DNA signature of homologous recombination deficiency,” said Wolpin. “This alteration can lead to inherited breast and ovarian cancer, and targeted drugs are approved for patients with these diseases. However, since this mutation was detected in a patient's pancreatic cancer, we were able to treat him with these same drugs, and he has had no evidence of cancer on imaging studies more than two years after his diagnosis of metastatic disease. We believe that knowing the mutations in his tumor has allowed us to personalize his therapy.”

The researchers reported that 18 percent of the patients were found to have inherited mutations that likely predisposed them to pancreatic cancer. This finding adds to an increasing call for all pancreatic cancer patients to undergo germline testing, regardless of their age or family history.

"Our goal is for personalized treatment to become the standard for patients with pancreatic cancer, including through the genomic evaluation of inherited and tumor DNA plus other emerging strategies that characterize the vulnerabilities of each patient's cancer,” said Wolpin.