The conference, held in Boston, attracted more than 600 physicians and scientists, all of whom have a special interest in advancing research on and treatment of one of the most formidable of foes. Without a doubt, progress has been made in understanding the basic biology of this heterogeneous disease. And in many cases, this research has led to better treatments that can extend the lives of some patients. It’s also clear that more work needs to be done.
This year’s conference was opened by Andrew Rakeman, Vice President of Research for the Lustgarten Foundation. Cindy Price Gavin, Founding Executive Director of Let’s Win, announced a new logo and updated website coming in the fall. The science presentations brought together some of the leading voices from across the globe and featured more than 200 abstracts on various topics. Special plenary sessions were tightly focused on key topics, which included ongoing research on health disparities, early-phase clinical trials, prevention, treatment challenges facing patients with locally advanced disease, the immune response of pancreatic cancer, and discovery science relating to heterogeneity.
Let’s Win is bringing you a brief overview of these topics. And in the coming months, we will provide more in-depth reporting on many of the specific presentations relating to these interesting topics.
Health disparities are a problematic issue in many aspects of care delivery and research. Pancreatic cancer is no exception. Although there is not one magic bullet that can provide solutions to this problem, there is intriguing information on the issue of disparity in care delivery, clinical trials, and research. These disparities affect patient outcomes.
What was made clear is that focusing on genetics will miss key drivers of disparities. Rather, research should expand opportunities to address issues of access beginning at the discovery phase and then move forward to clinical trial design and eventually treatment. It is also important to consider that race is a social construct, and environmental obstacles and epigenetics are also sources of disparity.
There is no doubt that disparity is difficult to study, mostly due to the fact that social determinants of health are not included in clinical notes. Unfortunately, the population at the greatest risk of disparity is, not surprisingly, those communities that are often already marginalized: older adults, racial ethnic minorities, citizens of rural communities in states that have not expanded Medicaid, and members of the LGBTQ+ community. It should also be noted that standard pancreatic cancer clinical trial criteria are estimated to make many patients ineligible, including 42 percent of Black patients and 33.3 percent of white patients.
Bench to Bedside: The Science that Underpins Clinical Trials
These presentations focused on results from recent clinical trials with a variety of agents, including two successful phase I studies that are advancing to phase II. The detailed mechanistic analyses from phase II studies are revealing potential paths forward for patient stratification and precision medicine in pancreatic cancer. For example, data was presented from a successful phase I dose-finding study using an IL-1b inhibitor in metastatic patients. Due to encouraging responses in this phase I study, a phase II study has started and is now enrolling patients. Initial results from a novel agent blocking signaling from the growth factor GDNF also look promising, with potential impacts on tumor growth and cancer-associated cachexia. This is also moving into phase II.
This dovetailed with presentations focusing on Tumor Plasticity and Drug Resistance. Basic science is yielding a better understanding of the heterogeneity and plasticity of human disease. Novel technologies are being used to better understand pancreatic cancer subtypes and how these subtypes change with treatment. Researchers are also focused on gaining a better understanding of the earliest events that eventually lead to full-blown pancreatic cancer.
Challenges in Treating Pancreatic Cancer
Many terms can be used to define the extent and severity of pancreatic cancer. The term “locally advanced” means that cancer has not spread far beyond the pancreas, but has advanced to the point where it cannot be surgically removed. However, no two cases of pancreatic cancer are the same. Some patients with locally advanced pancreatic cancer may undergo surgery to remove a portion of the tumor, while others rely on nonsurgical therapies to help reduce symptoms and slow the spread of cancerous cells. Locally advanced pancreatic cancer is typically associated with patients in stage III of the disease as determined by the tumor, nodes, and metastasis grading system.
Patients with locally advanced disease are very challenging to treat, as evidenced by several presentations. But there are also opportunities. Unfortunately, until recently this cohort was relatively understudied and, therefore, difficult to treat. Review of clinical trials, approaches, and research to better understand heterogeneity of population and biology of metastases is ongoing. In “Challenges in Treating Locally Advanced Pancreatic Cancer,” it was also made clear there is an opportunity to treat this stage more effectively. About 20,000 patients yearly in the U.S. are diagnosed at this stage, but generally these patients are not eligible for most clinical trials. These patients also require the most intensive, multidisciplinary care. The key is to look for solutions and move more quickly to combination therapies and more personalized approaches.
In general in pancreatic cancer, there is a great need for more science- driven trials and approaches that take into account systemic inflammation and cachexia at onset. Unfortunately, pancreatic cancer has the lowest phase III success rate—10 percent vs. 40 percent for all oncology. Phase I success rate is also low and not improving, unlike for melanoma. There is a great need for identifying biomarkers to match patients to therapy. And there is also a need for rational combinations and statistical methods to be able to do trials with smaller numbers of patients to yield more effective results.
Prevention and Interception
The prevention of pancreatic cancer as well as interception at the earliest possible phase of the disease is the Holy Grail of research. To be successful in their efforts, researchers must hone their ability to identify individuals at high risk based on the presence of benign lesions or family and medical history. Studies are ongoing to prevent progression of pancreatic cancer using anti-inflammatory and vaccine approaches. Investigations into the biology of risk and early disease to better understand the processes driving how pancreatic cancer starts are also being examined.
Tumor Microenvironment, Immunobiology, and Immunotherapy
Research into better understanding how the environment surrounding the tumor can contribute to disease progression is also ongoing. The tumor microenvironment, or TME, opens many avenues for intervention. Research into understanding the interaction between tumor, TME, and the immune system is leading to new approaches to immune therapy for pancreatic cancer. Work on B cells, engineered T cells, cytokine signaling, and neural interactions are also ongoing.