Genetic Sequencing of Advanced Pancreatic Cancer Enables Personalized Medicine

Illustration Of A Gold-colored Double Helix DNA Strand Against A Blue-gray Background
Mehmet Pinarci; Flickr
Lustgarten-funded research impacting patients in real time.

In a study published on June 14, 2018 in Cancer Discovery, genomic analyses of metastatic pancreatic cancers have suggested that approximately one third of pancreatic cancer patients may have a genomic alteration that could impact treatment decisions and guide doctors to choose a specific therapy for a personalized medicine approach. This work was funded by the Lustgarten Foundation and the Hale Center for Pancreatic Cancer Research at Dana-Farber Cancer Institute.

“These results suggest that knowing the genetic make-up of advanced pancreatic cancer can impact patient care,” said Lustgarten-funded researcher Brian Wolpin, M.D., MPH, Dana-Farber Cancer Institute. “One example highlighted by this work is a patient whose tumor has a somatic BRCA2 mutation with a DNA signature of homologous recombination deficiency. 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 in a way that would otherwise not have been possible.”

The study describes a metastatic tumor biopsy protocol at Dana-Farber, called PancSeq, which was implemented in order to perform whole exome sequencing (DNA) and RNA-sequencing for patients with advanced pancreatic cancer. Additionally, both tumor DNA and inherited DNA were sequenced for all patients. The analyzed data was then given to their clinicians to assist in the patients’ care. Most patients had metastatic disease (96%) and no prior treatment (70%).

Topline Findings

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. Overall, 30% (21/71) of enrolled patients had a change in their clinical care as a result 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 data demonstrate how the timely collection of genetic information can impact treatment decision-making in pancreatic cancer through enrollment of patients to clinical trials or the use of off-label targeted therapies. Furthermore, only with well-designed clinical trials can new treatment approaches be identified and shown to be beneficial for patients with pancreatic cancer.

“Using PancSeq, we demonstrated that genomic characterization of advanced pancreatic cancer can identify relevant mutations and inform clinical decisions for patients with this difficult disease,” Dr. Wolpin said. “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.”