Diagnosed in about 55,000 Americans each year, pancreatic cancer is predicted to become the second leading cause of cancer death, behind only lung cancer, by the year 2020, according to a research review published in June 2016 in Future Oncology. While pancreatic cancer accounts for only 3 percent of malignancies in the United States, it has a high mortality rate and accounts for about 7 percent of all cancer deaths, according to the American Cancer Society. “The survival rate has been the lowest of the major cancers for too long,” Dr. Matrisian says. “We’re starting to move that needle, but there’s still a long way to go.”
Challenge 1: Pancreatic Cancer Is Hard to Diagnose Early
One major issue is that the disease is difficult to detect early, when it’s easier to treat. “The pancreas is located deep in your body, so there’s no obvious lumps or signs people would detect easily,” Matrisian says. Also, people often don’t recognize symptoms for what they are, and for good reason. “The symptoms are pretty common — back pain, indigestion — the types of things you see a lot, especially as you get older,” says Matrisian.
Challenge 2: Typical Imaging Tests Don’t Catch Tumors Early and Cost Too Much
Unlike other malignancies, such as breast or colorectal cancer, which can be detected by widely available screening tests, standardized screening tests for pancreatic cancer (such as MRI, ultrasound, or CT imaging) are not particularly good at detecting early disease, thus not financially practical as prescribed screening tests. The ideal imaging test would detect cancer “at a very, very early state, where the disease burden is low and lesions might be small,” says Kevin Roggin, MD, a professor of surgery and a cancer researcher at University of Chicago Medicine. So far, that kind of testing doesn’t exist.
Advance 1: Improved Surgical Approach Makes It Available to More People
Extensive surgery to eliminate pancreatic cancer remains the best shot at a cure, experts say. But, in the past, most people were diagnosed too late to be eligible for the operation, known as the Whipple procedure, which typically involves removing the head of the pancreas, the entire gallbladder, and parts of the bile duct, small intestine, and stomach. Now doctors have learned that shrinking pancreatic tumors with chemotherapy or radiation before attempting surgery makes more people eligible for the Whipple procedure. “We’re learning that preoperative therapy can be effective at identifying patients who may benefit from these operations and also in shrinking tumors attached to surrounding structures, like blood vessels, that previously limited these operations,” says Dr. Roggin. “There’s great momentum toward a paradigm that involves up-front chemo or chemo combined with radiation before doing these very aggressive operations.”
Advance 2: Improvements in Chemotherapy Are Upping Survival
Chemotherapy options for pancreatic cancer have also improved over the past decade, extending survival time for people with the disease. Adding a drug called Abraxane (paclitaxel) to the mainstay drug, Gemzar (gemcitabine), has helped people with advanced disease live longer and lengthened the time before the cancer advances, according to a study published in October 2013 in The New England Journal of Medicine. Increasingly, doctors are also using a chemotherapy regimen known as FOLFIRINOX, which contains a drug combination that includes fluorouracil, leucovorin (Wellcovorin), irinotecan (Onivyde, Camptosar), and oxaliplatin (Eloxatin). Research presented at the 2018 annual meeting of the American Society of Clinical Oncology found that people who’d had surgery to remove their tumor and were then given FOLFIRINOX rather than Gemzar were significantly more likely to be alive three years later (64 percent versus 48 percent); they were also less likely to have metastases. “If a patient is healthy enough to get four drugs compared to two or one, we tend to try FOLFIRINOX,” Matrisian says, though she adds there is an ongoing debate about the optimal approach. “We consider them both as a standard of care.”
Advance 3: Targeting Genetic Mutations
At the 2019 meeting of the American Society of Clinical Oncology, news broke that people with pancreatic cancer who have inherited a BRCA mutation, which is known to increase the risk for the disease, responded well to a drug called Lynparza (olaparib). People with a BRCA mutation who had completed chemotherapy were sorted into two groups: one received Lynparza, while the other got a placebo. After three years, 22.1 percent of the people in the Lynparza group had experienced no progression of their disease, compared with 9.6 percent in the placebo group. There are other advances in this arena, as well. PanCAN’s patient call center helped coordinate DNA sequencing tests for more than 600 people over the last several years, Matrisian says. More than one-quarter were found to have a highly actionable gene mutation for which an already available drug had been shown to work in another tumor type. A small number of those people, after receiving the targeted therapy, showed a statistically significant survival benefit, as compared to peers treated with standard therapy. “In my mind, there’s a lot of potential there,” Matrisian says. “We’ve shown it can work for pancreatic cancer, and my assessment is that it’s worth doing. Even if it helps a small percentage, it’s very meaningful for that small group and it’s doable.” Other future-focused treatments include these initiatives:
Certain drugs help break down the stroma, a scarlike tissue that helps pancreatic tumors evade the effects of chemotherapy. One such agent currently being investigated is pegylated recombinant human hyaluronidase PH20, which targets a protein in the stroma believed to be responsible for blocking chemotherapy drugs.Immunotherapy, an increasingly used treatment in other solid tumors, is also being tested in pancreatic cancer, Matrisian says. Keytruda (pembrolizumab), which is in a category of drugs known as a checkpoint inhibitors, has also been shown to effective in some people with pancreatic cancer. Researchers are looking into combinations of immunotherapies and combinations of immunotherapies with treatments like radiation to see if they will be effective against the disease.
“My sense is we’re making progress on each of these fronts individually, and it’s a matter of time where we can learn enough to start putting them together,” says Matrisian. “I think there’s a bright future, and it can’t happen soon enough.”
