Tumor Biology Matters

Where there is a will, there is that proverbial way.

That’s what Lynn Matrisian, Ph.D., M.B.A., and her colleagues at the advocacy organization Pancreatic Cancer Action Network (PanCAN) discovered more than six years ago when they first broached the subject of developing a program that would help doctors match treatment to the molecular profile of a patient’s tumor. After all, molecular profiling coupled with precision medicine had already changed and improved the treatment landscape of other cancers.

But pancreatic cancer was supposedly different. It’s no secret the disease is tough to treat, seemingly defying every drug that’s thrown at it. It’s often diagnosed in later stages when surgery, the only potential cure, isn’t an option. “We heard everything from ‘You aren’t going to be able to get tissue,’ ‘The disease moves too fast,’ ‘What are you going to target?’ ‘It’s all KRAS-driven,’ to ‘It’s simply not going to work,’” recalls Matrisian, PanCAN’s Chief Science Officer. “But we felt that we owed it to the patients to advance the science, to keep trying. We felt an absolute obligation to test the hypothesis.”

Well, that hypothesis has yielded some important results. An analysis of patients enrolled in a PanCAN program called Know Your Tumor® showed that those patients who could be matched to a treatment geared to the specific molecular profile of their tumors lived longer, according to a study published in Lancet Oncology in March 2020. Those that received standard chemotherapy had a median overall survival of 1.51 years. Patients that received a targeted therapy matched to molecular changes in their tumor had a median overall survival of 2.58 years, living one year longer, on average, compared to the standard chemotherapy cohort. This is the first study of its type to demonstrate this overall survival benefit from precision medicine in pancreatic cancer patients.

“To say we were thrilled is kind of an understatement,” says Matrisian, study co-author. “This is real-world data, with real-world patients whose lives were extended.”

About the Study

The Know Your Tumor (KYT) study was a joint effort of PanCAN and Perthera Inc., a precision medicine company. The retrospective study was designed to include data from pancreatic cancer patients of all stages who had agreed to molecular testing of their tumors and subsequent molecularly-tailored treatment options or clinical trials. The primary outcome measure of the study, which was median overall survival, was calculated from the point of initial diagnosis of advanced disease until death.

• About 25 percent of pancreatic cancer patients registered in the program who received molecular testing (282 of 1,082) were found to have tumors that harbored molecular changes that were potentially susceptible to targeted therapies. Treatment outcomes were only available for 189 of these patients because some had died before the report could be delivered and others had no documented information about their treatment.
• Of those, 46 patients received as one of their treatments a targeted therapy matched to the specific molecular change associated with their tumor.
• The researchers found the average survival for those who received a targeted therapy was a little over two and a half years (31 months). Average survival for patients who did not have one of the molecular changes for which a targeted therapy exists, and had been treated with standard chemotherapy, was 16 months.
• 143 patients were eligible for a targeted therapy because they had tumors carrying one of the relevant molecular changes, but had been given standard chemotherapy. Their average survival was 18 months.

“I think what the study shows is that there is true benefit in molecular profiling of pancreatic cancer patients on a routine basis,” Matrisian says. “There are actionable targets and some pancreatic cancer patients can absolutely benefit.”

It should be noted that in 2018, the National Comprehensive Cancer Network issued new pancreatic cancer guidelines recommending that all pancreatic cancer patients get a large enough tissue sample during diagnosis for tumor molecular profiling, and in 2019 the guidelines were updated to recommend that patients who can get more treatment have their tumor tested. In addition, they added the recommendation for genetic testing for inherited genetic mutations, regardless of family history. These changes signify adoption of the concept of precision medicine for pancreatic cancer, adds Matrisian.

About KYT and Molecular Profiling

The KYT program focuses its efforts on the unique biology of an individual patient’s tumor. The tumors are tested for inherited genetic mutations through germline testing as well as somatic testing (for random mutations) with molecular profiling, basically analyzing the DNA, RNA, and protein in cancer cells that can also provide clues for the best treatment approach. Specific approved treatments, as well as off-label medications that have shown promise in other cancer types, may be recommended. Clinical trials may also be an option. Tissue samples are analyzed and reports are emailed to an individual’s physician and the patient so that options can be discussed.

PanCAN has a robust explanation of the KYT program on its website, covering a multitude of questions both from the patient and physician perspective. Their Patient Central program can also be contacted.

For Matrisian and her colleagues throughout the pancreatic cancer community, the entire effort is one big step in the right direction. “Within the pancreatic cancer community there is a real sense of kinship,” she says. “We all know each other, the researchers and clinicians from different institutions are supportive of each other, the advocacy groups help each other out, and there is a real bond among the patients.”

She continues, “What all of us are focusing on is improving the outlook for pancreatic cancer. All of us talk about the future, and what we would like to see. Of course, we all want better treatments for all pancreatic cancer patients.

“People need to understand there is a huge and positive difference in treatment approaches being made right now through a better understanding of tumor biology. And for those patients for whom targeted treatments can help, well, it’s been worth every bit of effort.”

Let’s Win would like to thank PanCAN and the army of dedicated physician-scientists, clinicians and researchers, cancer advocacy groups, and most of all, the brave patients who have brought the importance of molecular profiling to the forefront of pancreatic cancer. It is through the dedication of these groups that we will make great strides in the treatment of the disease.