How an Expert Would Manage His Own Stage 4 Pancreatic Cancer: An Update

When confronted with a new cancer diagnosis, some people ask their doctors, “What would you do if you were me?” Previously, our Curious Dr. George asked John H. Strickler, MD, how he would handle his own hypothetical diagnosis of metastatic pancreatic cancer. Now, Dr. Strickler provides an updated answer, outlining new options for the nearly 95% of pancreatic cancer patients with KRAS mutations. Dr. Strickler is Associate Professor of Medicine in the Division of Medical Oncology at Duke University and Co-Leader of the Duke Molecular Tumor Board.

Curious Dr. George: Cancer Commons provides information about options to patients with advanced cancer, usually beyond standard of curative care. As an experienced academic and practicing clinical oncologist at Duke University, you have particular interest, training, and experience in gastrointestinal cancer.  What would you do if you personally were discovered to have an asymptomatic, unsuspected, ductal adenocarcinoma of the tail of the pancreas that had already metastasized to your liver?

John H. Strickler, MD: Pancreatic cancer remains one of the most lethal malignancies. Advancements in chemotherapy, immunotherapy, and targeted therapies have helped countless people with advanced solid tumors, but for pancreatic cancer most of these advancements have not made a meaningful impact. However, despite the grim survival statistics and poor prognosis associated with this disease, there is reason to have hope. With improvements in supportive care, chemotherapy, and molecular diagnostics, some patients are living longer and living better. While we have a long way to go, finally progress is being made.

If I were diagnosed with metastatic (stage 4) pancreatic adenocarcinoma, the first thing I would do is find an experienced multi-disciplinary team. This team would give me the best outcomes possible. Members of this team would include experts on the following fields:

Medical Oncology: Although the primary function of the medical oncologist is to provide chemotherapy, typically he or she formulates the treatment plan and coordinates care. In my hypothetical case, the medical oncologist would recommend either gemcitabine alone, gemcitabine with nab-paclitaxel, or FOLFIRINOX. All of these treatments would be reasonable, but combination chemotherapy (gemcitabine + nab-paclitaxel or FOLFIRINOX) would offer the greatest disease control and longest survival.

Additionally, the medical oncologist would be responsible for ordering next-generation sequencing on my tumor tissue to determine if my tumor harbors an “actionable” genetic alteration. Although these actionable genetic alterations are rare, they may make me eligible for immunotherapy or other targeted therapies. Nearly 90% of patients with pancreatic cancer have a KRAS mutation, and advancements in drug chemistry are finally making KRAS “druggable.” KRAS^G12C mutations are now considered treatable with highly selective KRAS inhibitors, such as sotorasib or adagrasib. Inhibitors of other more common KRAS mutations are now entering the clinic. We are all hoping to see more breakthroughs.

Genetic counseling: Approximately 5% of all patients with pancreatic cancer have a germline (hereditary) mutation in BRCA1/2 or PALB2, and these hereditary mutations predict benefit from platinum-based chemotherapy and PARP inhibitors. Other rare germline mutations can also predispose a patient to pancreatic cancer. Current national guidelines advise germline testing in all patients diagnosed with pancreatic cancer, regardless of family history. Genetic counseling is advised for any patient who tests positive for a pathogenic germline mutation or has a strong family history.

Palliative care: Many patients are hesitant to consider palliative care. There is a misconception that palliative care represents end-of-life care. I hope that we can change this misconception. Pancreatic cancer often presents with complicated symptoms that are difficult to manage. Even if I present completely pain free, symptoms from pancreatic cancer can change rapidly. Given the incurable nature of this disease, it is helpful to have a team of doctors who can help me and my family prepare for the future. I view palliative care as a critical “extra layer of support” to fight a very difficult illness.

Other important members of the team: As a medical oncologist, I have learned that I am only as good as the people around me. I cannot overstate the importance of having experienced and dedicated nurses, advanced practice providers (NPs and PAs), and clinic staff to provide extra support. Additionally, by finding a skilled multi-disciplinary team for my hypothetical diagnosis, I would have access to other experts, including radiologists, pathologists, surgeons, radiation oncologists, and gastroenterologists. All of these physicians would be key to my health and symptom management.

Final thoughts:

As a gastrointestinal medical oncologist, I have seen how difficult pancreatic cancer can be for patients and their loved ones. This remains a disease with high symptom burden and poor outcomes. If I were facing this disease myself, I would recognize that it takes a community of dedicated clinicians to keep me living longer and living better. As a patient, I would make myself available to clinical trials and other research. It is through these research efforts that we will change the course of this terrible disease and improve outcomes.

More details about ways to support pancreatic cancer research and resources for patients and families fighting this disease can be found at the Pancreatic Cancer Action Network.

Dr. Strickler can be reached at john.strickler@duke.edu.