LustgartenLIVE! From the Clinic to the Lab, to YOU

Pancreatic cancer is like playing chess, not checkers.

With the steadfast determination and focus needed to succeed at chess, we see tremendous momentum in pancreatic cancer research, translating to better patient outcomes. We have recruited the best and the brightest scientists and clinicians to work on pancreatic cancer because they rise to the challenge of conquering this difficult disease. In celebration of National Doctor’s Day, Lustgarten convened a roundtable of experts across the cancer continuum to discuss care today and what breakthrough developments in research mean for patients.

David Tuveson, MD, Ph.D., Chief Scientist of the Lustgarten Foundation and Director, Lustgarten Foundation Dedicated Laboratory at Cold Spring Harbor Cancer Center, moderated the program, referring to the fortitude needed to cure pancreatic cancer as a game of chess, not checkers. Over the last several decades, we have many more options to offer patients, largely due to the early efforts in the laboratory that are now translating into the clinic. We are beginning to use drugs that target the underlying molecular causes of pancreatic cancer and are working to leverage the immune system to help fight the disease. Finally, our pawns are advancing!

Dr. Tuveson introduced the panel of “dynamic, creative, and empathic physicians,” including Domenech Asbun, MD, Miami Cancer Institute, Daniel A. King, MD, Ph.D., Northwell Health Cancer Institute, Allyson J. Ocean, MD, New York-Presbyterian Hospital/Weill Cornell Medical Center, Mark H. O’Hara, MD, University of Pennsylvania, and Eileen M. O’Reilly, MD, Memorial Sloan Kettering Cancer Center to participate in a discussion highlighting the newest breakthrough for patients.

How Personalized Medicine is Helping Patients

Dr. Eileen O’Reilly has been instrumental in designing clinical trials for patients with BRCA and related mutations, translating into a new standard of care therapy for this subgroup of patients. This is the essence of personalized medicine. A patient’s tumor is sequenced to look for alterations in the DNA and treated with therapies specifically targeting these alterations. Platinum therapies and PARP inhibitors have become the standard of care for patients with BRCA and related mutations. We’re now building on this by testing combinations of PARP inhibitors with immunotherapy.

An expert in immune therapy, Dr. Mark O’Hara, explained that cancer likes to evade the immune system so it can continue to grow. Training the immune system to recognize cancer has led to effective treatment in multiple cancers, but not yet for most pancreatic cancer patients. Dr. O’Hara and others are working on many clinical trials testing different combinations to harness the immune system in pancreatic cancer. The first breakthrough in immunotherapy was a treatment for advanced pancreatic cancer patients whose tumors have a specific alteration called mismatch repair deficiency. The Lustgarten Foundation played a critical role in bringing this new treatment to patients by funding the research, encouraging patients to get tested, and funding patients’ testing to determine if their tumors are mismatch repair deficient.

Whack-a-mole

Dr. Allyson Ocean sees many patients who have exhausted the standard treatment options. Ocean commented that while working on pancreatic cancer is more like chess than checkers, she terms her approach scientific whack-a-mole. At the point when one therapy stops working, she turns to the latest science to ask what can be done now to potentially give a new whack to this cancer? Sometimes that may not necessarily be chemotherapy. It may be localized therapy such as radioembolization or a Y90 treatment to a dominant liver mass that is causing pain or blocking the bile duct. She closely follows new cutting-edge procedures and devices, mentioning an ongoing clinical trial of a device that delivers high-frequency ultrasound waves across the abdomen to try to disrupt cell division. Another device used in glioblastoma patients used to break down the growth of brain tumors is now being tested in pancreatic cancer in combination with chemotherapy. Ocean sometimes identifies off-label drugs for patients with specific mutations and uses organoids of a patient’s tumor to test which drugs could be the most effective in treating that individual’s cancer. While she does use standard therapies, Ocean always also seeks out trials for patients. This led to her being a founder of Let’s Win Pancreatic Cancer, an online community for sharing information about innovative, science-based treatments for pancreatic cancer, and an affiliate of the Lustgarten Foundation.

Checkmate! The watershed moment

Dr. Daniel King noted that while we have better treatment options for people with rarer genetic mutations such as BRCA or mismatch repair, the watershed advance is coming through new therapies targeting the KRAS gene, mutated in most pancreatic cancer patients. Progress in developing treatments attacking it has been slow until now. Last year, the FDA approved a new therapy designed to treat people with one form of the KRAS mutation prevalent in advanced lung cancer and a small subset of pancreatic cancer patients. The watershed advance King is talking about would come from drugs that target the more common forms of KRAS in pancreatic cancer. Clinical trials, supported by Lustgarten and others, are beginning this year and could be the game-changer for pancreatic cancer.

What’s on the horizon for surgical patients?

The tumor in the pancreas sometimes invades the blood vessels surrounding the pancreas, making surgery difficult and riskier for patients. Whereas once these patients were considered inoperable, Dr. Asbun noted that the practice of surgery has changed significantly in the past few years, bringing many more patients to potentially life-saving operations. He and his colleagues have been using chemotherapy or radiation therapy to shrink the tumor before surgery, making it easier and safer to remove. He noted that the nano knife has shown some promising early results, where the tumor is essentially electrocuted with probes that cause the tumor cells to collapse and die off.

Additionally, today surgeons sometimes can use minimally invasive approaches when operating on pancreatic cancer patients. Instead of traditional surgery through a big, long cut, laparoscopy or a surgical robot can perform the surgery, making the impact and recovery less intense.

Being your own advocate in patient care

Patients and doctors should make decisions as a team. The panel offered the following advice:

Treatment and Clinical Trials

• Approximately 30% of people diagnosed with pancreatic cancer are never offered treatment. Patients should always seek a specialist aware of the latest treatment options and available clinical trials.
• Receiving treatment at a center of excellence leads to better outcomes.
• Consider participation in a clinical trial. It is a misconception that patients that participate in clinical trials are guinea pigs. While clinical trials are designed to determine if a specific treatment is safe and effective, many patients see a response and do better in trials than with the current standard of care treatments.
• The pandemic saw the advent of remote clinical trials, which may be here to stay. Check with your doctor on a remote trial, as this can help reduce the burden of taking part in a trial.
• Clinical trials are available for patients at all stages and steps in their journey – from first-line treatments to patients that have been previously treated. Clinical trials will each have specific inclusion criteria, and all patients won’t be eligible for all clinical trials, but many clinical trials are available for second-line or later treatment. Patients and caregivers can search for available clinical trials and eligibility using a clinical trial matching tool developed by Lustgarten and Let’s Win.

Genetic sequencing for the patient and familial risk

• Insurance covers tumor sequencing for patients at diagnosis to see if a mutation might change the treatment plan. Ensure your doctor sends your tumor to be sequenced and can interpret the information so that that information can help you.
• More genetic mutations have surfaced in the past few years, so if you had genetic testing many years ago, check with your doctor to see if you should be retested.
• If the sequencing shows a known mutation, family members should seek out the advice of a genetic counselor and make their primary care doctor aware of the family history. Family members may be screened more often for pancreatic and other cancers attached to familial syndromes.
• While most pancreatic cancer is not due to inherited risk, if you are concerned, ask your doctor for a referral to a genetic counselor to explore the possibility of inherited risk and genetic testing.
• Individuals with a strong family history of pancreatic cancer or a known genetic syndrome may qualify for endoscopic ultrasound or MRI.

Pancreatic Cancer Basics

• The more common symptoms of pancreatic cancer are abdominal pain, nausea, pain after eating, back pain, unintended weight loss, loss of appetite, dark urine and light stool, jaundice, and depression. Additionally, risk factors include new-onset diabetes and acute pancreatitis attacks. Approximately 1% of people diagnosed with late-onset type two diabetes develop pancreatic cancer.
• Pancreatic cancer is difficult to detect early for many reasons. First, the pancreas is located where the early tumors cannot be seen or detected by providers during routine exams. Another factor is that patients usually do not have symptoms until the tumor has grown to a large size or has already spread to other organs.
• Currently, there is not a screening test that can detect pancreatic cancer at an early stage. Lustgarten supported researchers are working to develop methods and tests that will enable early detection. The CancerSEEK blood test will soon go into a large registration trial to lead toward a routine blood test in the doctor’s office. The Felix Project harnesses the power of machine learning to detect tiny, early-stage tumors on CT scans.
• In addition to early detection, approaches to early intervention and interception of pancreatic cancer are making headway. A first-of-its-kind vaccine trial to prevent pancreatic cancer in high-risk healthy individuals is now open.
• The likelihood of recurrence depends on various factors, such as the stage of the tumor at the time of surgery, size, and type of tumor, so it is important to continue to make routine visits with your doctor for surveillance. Imaging is used to surveil for recurrence of the disease. One type of research currently under investigation is Minimal Residual Disease testing on the blood to look for mutations in the bloodstream specific to the tumor and may suggest recurrence. This approach is now being used in colon cancer and under exploration for pancreatic cancer. Additionally, to improve your chances of not having a recurrence, eat healthy foods, exercise, and avoid tobacco.

In honor of National Doctor’s Day, the Lustgarten Foundation thanks the professionals for their dedication and contributions to improving the quality of life for patients and helping transform pancreatic cancer into a curable disease.

Additionally, we are grateful for our sponsors and the entire Lustgarten community whose support helps us wield the power of research to extend lives. Community is Power. Together we can make an impact.

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