Deadly and defiant, pancreatic cancer was one of the major oncologic threats Congress hoped to address with passage of the “Recalcitrant Cancer Research Act,” which was signed into law at the beginning of 2013.
Garnering broad bi-partisan support, the statute honed in on cancers with five-year relative survival rates below 50 percent. Starting with pancreatic and lung cancer, the law calls for the National Cancer Institute to develop a scientific framework and strategic plan to move the science forward at a more rapid pace to address these deadly diseases.
Leading the call to pass the legislation and increase research, collaboration and patient resources is the Pancreatic Cancer Action Network (PanCAN). Formed in 1999, the California-based national organization will have awarded almost $23 million in grants to 110 research scientists around the country by year’s end. Additionally, the Patient & Liaison Services (PALS) has shared current, reliable information with more than 80,000 patients and family members, including a comprehensive clinical trials database to link patients with the latest treatment options and research studies.
A PanCAN research study published in Cancer Research this past May predicted pancreatic cancer would become the second leading cause of cancer-related deaths by 2020 and also estimated the increase in liver cancer deaths would make lung, pancreas, liver and colorectal the top four cancer killers in the country by 2030.
“When we think of ‘big picture’ cancers, we think lung, breast, prostate and colorectal,” said Lynn Matrisian, PhD, MBA, vice president of scientific and medical affairs for PanCAN. More than 800,000 Americans will receive a diagnosis of one of these types of cancer this year (see box).
Yet, noted Matrisian, pancreatic cancer, which is the 12th most commonly diagnosed cancer, is currently the fourth leading cause of cancer deaths in the United States. “Pancreatic cancer surpassed prostate cancer a couple of years ago and is expected to surpass breast cancer in the next year or two and the colorectal cancers around 2020,” she explained.
While great strides are being made in lowering overall cancer death rates, Matrisian said it has been much more difficult to gain traction in improving pancreatic cancer survival. “For pancreatic cancer, we haven’t made any change much at all in the death rate since we began keeping records. The five-year survival rate is 6 percent. An estimated 73 percent of patients die within the first year of diagnosis.” She added, “It’s the only one of the major cancers with that five-year survival rate in the single digits.”
The reasons for the high mortality rate are multifactorial and include a need to better understand the pathogenesis of the disease and to identify it earlier when treatment options have a greater opportunity for success. “The pancreas is deep within your body. The symptoms are pretty vague and can be attributed to multiple diseases so it’s often diagnosed quite late,” Matrisian said. She added, an aging and growing population is anticipated to increase the number of cases of pancreatic cancer in coming years, which in turn is expected to lead to pancreas cancer becoming the number two cancer killer considering its mortality rates.
Yet, she stressed, “It doesn’t have to happen if we can change things now.” Matrisian said she sees the information as a call to action and pointed to the preventive, diagnostic and treatment successes that have occurred in many diseases through focused research efforts.
Stand Up To Cancer (SU2C) is answering that call with the formation of their second pancreatic cancer Dream Team. Announced in April, the SU2C-Lustgarten Foundation Pancreatic Cancer Convergence Dream Team is focused on immunotherapy and is being led by noted physician-scientist Elizabeth M. Jaffee, MD, professor of oncology at Johns Hopkins School of Medicine and co-director of the Gastrointestinal Cancers Program at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins in Baltimore.
University of Pennsylvania translational research expert Robert H. Vonderheide, MD, DPhil, has joined Jaffee as co-leader of the project — “Transforming Pancreatic Cancer into a Treatable Disease.” The multidisciplinary team includes seven other principals from around the country plus three patient advocate members. Funding for the $8 million, three-year grant is a collaborative effort of SU2C, The Lustgarten Foundation and the Fox Family Cancer Research Funding Trust.
The Dream Team will use the grant to develop new therapies to engage a patient’s own immune cells in the battle against pancreatic cancer. Jaffee has led the charge on creating an immunologic response, developing a novel pancreas cancer vaccine with colleagues more than a decade ago targeting pancreatic ductal adenocarninomas (PDAC), the most common form of pancreatic cancer.
“Pancreatic cancer suppresses the body’s anti-tumor immune response,” Jaffee explained. “These tumors do not allow immune cells that can recognize and kill them to even enter the pancreas. We think we can use vaccination to activate anti-tumor immune cells and then use other agents to get those cells into the pancreas where they can attack the tumor.”
Most recently, she noted, “We tested our newer vaccine, which is a combination of two vaccines – the first primes the immune system and the second targets cancer cells – and we now give a boost to the immune system.” She continued, “We’ve tested this in advanced patients who have failed all other chemotherapies, and we showed it significantly improved survival.”
Jaffe added the median survival doubled from three months to more than six-and-a-half months. “Patients who did well are doing well long-term,” she added, noting some of these advanced patients have now survived more than a year out from the immunotherapy. “There really aren’t side effects so the patients have a better quality of life,” she added of another plus. The outcomes have resulted in accelerated approval status from the Food & Drug Administration.
While Jaffee and her colleagues at Johns Hopkins have made important progress, she noted bringing the Dream Team together will enhance everyone’s work. “Each center has come up with a project based on the science they were developing,” she said of the two Phase I studies and three multicenter Phase 2 trials being launched. “We’re going to combine now and share our technologies to analyze the different clinical trials. We’ll compare mechanisms to see if we should combine agents,” Jaffee continued.
Calling the Dream Team an “all out massive attack on pancreatic cancer,” Jaffee said it is a wonderful opportunity to bring experts from eight different centers together to advance pancreatic research. She also said it’s possible immunotherapy could be widely available to patients in the next two years pending outcomes of current trials.
While improved treatment clearly would be a critically important advance, Jaffee said there is another exciting development underway. She and her team have recently published their first paper showing prolonged progression of the disease in animal models.
“We don’t know when the first genetic changes are occurring and at what age,” Jaffee noted. However, she continued, “Cancer starts to develop 20-30 years before you see it.” By looking for early changes, such as mutated KRAS, the hope is to target a pre-malignancy and keep it from ever developing into pancreatic cancer.
“Our goal is to eventually prevent this disease from the start,” Jaffee concluded.
Estimated Cancer Cases & Deaths for 2014
The American Cancer Society’s “Cancer Facts and Figures 2014” outlines estimated incidence and mortality from the 12 most common types of cancer (as defined by having an estimated annual incidence for 2014 of 40,000 cases or more). While pancreatic cancer is at the bottom of the list when it comes to new diagnoses, but ranks number four in terms of estimated deaths.
Cancer Type Est. New Cases Est. Deaths
Breast 235,030 40,430 (3)
Prostate 233,000 29,480 (5)
Lung (Including Bronchus) 224,210 159,260 (1)
Colorectal 136,830 50,310 (2)
Melanoma 76,100 9,710
Bladder 74,690 15,580
Non-Hodgkin Lymphoma 70,800 18,990
Kidney 63,920 13,860
Thyroid 62,980 1,890
Endometrial 52,630 8,590
Leukemia (All Types) 52,380 24,090
Pancreatic 46,420 39,590 (4)
Resources for Your Practice & Your Patients:
PALS: The Pancreatic Cancer Action Network’s Patient and Liaison Services (PALS) offers one-on-one support and educational information. Patients and family members can call 877-272-6228 or email email@example.com. Additional information is also available online at pancan.org under the “Facing Pancreatic Cancer” tab.