Precision Medicine from the Get-Go for Pancreatic Cancer

Mike Mitchell; Dr. Bruce Chassey Laboratory. National Institute Of Dental Research

Many people are talking about a revolution when it comes to precision medicine.

Dr. Ben George prefers to discuss its potential in the evolution of existing therapies. George, an oncologist at Froedtert Hospital and Associate Professor of Medicine at the Medical College of Wisconsin, believes precision medicine can be successfully incorporated into the early stages of pancreatic cancer treatment, without straying far from the current standard of care.

Rather than wait years for drugs to be developed or new genomic-based treatments to be approved, George and his colleagues are working with what they already have—but in a smarter way. They are using genomic tools to guide treatment selection and sequencing.

Testing in a Clinical Trial

In the first trial of its kind in early stage pancreatic cancer, the MCW’s pancreatic cancer team conducted real-time molecular analysis of the tumors of 130 patients to determine which chemotherapy regimens were likely to be the most effective based on the biology of each tumor. They looked for protein expression signatures that are known to be linked to sensitivity to specific drugs/drug combinations, such as the transporter ENT1, which is tied to chemotherapeutic gemcitabine.

Patients then received the drugs based on their personalized genetic profiles. Those who were eligible for surgery received the drugs as neoadjuvant chemotherapy, before surgery. Additional tumor samples were taken during surgery and analyzed to guide post-operative decisions to treat any signs of lingering cancer.

Early results from the five-year trial indicate positive responses to the recommended therapies. Full results—analyzing resectability rate, overall survival rate, and progression-free survival—are expected within the year.

“We are very pleased with what we have found so far,” George says. More important to George and his team, however, is the fact that the approach has allowed more patients to complete the course of chemotherapy and subsequent surgery.

“We know patients typically do better when they complete all three treatment modalities: surgery, chemotherapy, and radiation,” says Susan Tsai, Associate Professor of Surgical Oncology at the Medical College of Wisconsin. But those who have surgery first can have a difficult recovery and may not be able to handle chemotherapy afterwards, she adds. “We thought if there’s a way to give them profile-directed therapy, maybe we can get more people to surgery.”

Applying Molecular Profiling to Treatment

The trial is part of a larger exploration into the use of neoadjuvant chemotherapy and alternative treatment sequencing that began in MCW’s Pancreatic Program in 2009.

The program’s approach to precision medicine is different in that they apply molecular profiling to the treatment of both metastatic and curable pancreatic cancer. George says he prefers to be a little more conservative in the curative setting.

“This is a group of patients we are trying to cure. There’s a limit to the liberties we can take,” George says. “We want to stay as close to the standard of care as possible. We don’t want to lose a curative window of opportunity.”

At the same time, the approach allows current patients to benefit from advances in precision medicine that have eluded them thus far. He notes, “If you are using genomics to fine-tune therapies to individual needs, you have achieved the goals of precision medicine.”