First person profile: Eileen M. O’Reilly, MD

Eileen M. O’Reilly, MD, has devoted her career to developing therapeutics for one of the most challenging and difficult diseases to treat: pancreatic cancer. Although advancements in treatments for many cancers have dramatically improved outcomes, pancreatic cancer remains among those for which effective treatments have lagged with few new therapeutic options.

However, that is changing. Research led by Dr O’Reilly, who holds the Winthrop Endowed Chair in Medical Oncology at Memorial Sloan Kettering (MSK) Cancer Center, has resulted in the first new therapy in more than a decade for treatment-naïve metastatic pancreatic cancer. In February 2024, the US Food and Drug Administration (FDA) approved NALIRIFOX (irinotecan liposome, oxaliplatin, 5-fluouroracil, and leucovorin) for the frontline treatment of metastatic pancreatic adenocarcinoma over the standard of care based on the results of the NAPOLI-3 trial.^{1, 2}

That is but one success story in Dr O’Reilly’s journey as a medical oncologist clinician–scientist. Her team defined the use of platinum-based therapy for BRCA-related pancreatic cancer based on the National Cancer Institute’s (NCI’s)–funded research,³ and this led to the updating of national guidelines. Applying what was known about the tumor-based genetics of pancreatic cancer, she also was involved in the early drug development of poly(adenosine diphosphate ribose) polymerase inhibitors as maintenance treatment for pancreatic cancer. She was a coauthor of the landmark phase 3 POLO study, which showed the superiority of olaparib over the standard of care as maintenance therapy for patients with metastatic pancreatic cancer with germline BRCA mutations and led to its FDA approval in 2019.^{4, 5}

Building on her work on the tumor-based genetics of pancreatic cancer, Dr O’Reilly is particularly excited about developments in KRAS-based therapeutics. Although it has been known for a long time that the KRAS gene is ubiquitous in pancreatic cancer, targeting it has been seen as actionable only recently, she says. Multiple drugs are currently in development and moving into phase 3 trials, she adds, and it is expected that this class of drugs will change outcomes in this disease.

Currently, working with her colleagues at MSK Cancer Center and collaborating with investigators at other institutions, Dr O’Reilly is focusing much of her research on the development of vaccines against pancreatic and other gastrointestinal cancers. Her ongoing research is aimed at two types of vaccines: new personalized antigen messenger RNA vaccines with systemic treatments (on which she and her MSK colleague, Vinod Balachandran, MD, are collaborating) and off-the-shelf KRAS-directed vaccines following standard adjuvant therapy for pancreatic cancer. Recently, she and her colleagues published preliminary evidence on the safety and efficacy of a KRAS-specific vaccine in inducing T-cell responses in patients with immunotherapy-recalcitrant KRAS-mutated tumors.⁶

Dr O’Reilly’s Irish roots are evident in her name, heard in her lovely lilting brogue, and expressed in her deep feeling of growing up as “a proud Dubliner.” In Dublin, she earned her medical degree at Trinity College and completed her residency in internal medicine and first fellowship in medical oncology at St. Vincent’s Hospital. She was inspired to pursue oncology through her work with oncologists Peter Daly, MD, and John Crown, MD, the latter encouraging her to pursue a fellowship in medical oncology at MSK Cancer Center.

That fortuitous fellowship placed her where she remains today. Dr O’Reilly is the primary investigator of the MSK Pancreas Specialized Program in Oncology Research Excellence, one of three NCI–funded team science grants currently awarded in the country specifically for pancreatic cancer. In her other administrative roles at MSK Cancer Center, she serves as the section head for hepatopancreatic biliary/neuroendocrine cancers in the Gastrointestinal Oncology Service, as codirector for medical initiatives at the David M. Rubenstein Center for Pancreatic Cancer, and as chair of the human research protection program and institutional review board. She is an attending physician at MSK Cancer Center and a professor of medicine at Weill Cornell Medical College.

Dr O’Reilly also serves as an associate editor for the Journal of Clinical Oncology (American Society of Clinical Oncology), senior editor for clinical trials for Cancer Research Communications (American Association for Cancer Research), and editor for gastrointestinal cancers for The Oncologist. She has published hundreds of articles, editorials, and book chapters.

Dr O’Reilly has received numerous awards and honors, including the Burkitt Medal (2022), in which she takes particular pride. Established in 2013 at Trinity College in Dublin and named after Denis Burkitt, MD (a Trinity graduate), who discovered Burkitt lymphoma and was seen as a medical social humanitarian, the award honors individuals for their extraordinary achievements and advancements in the field of cancer globally. More recently, she was named a Giant of Cancer Care in gastrointestinal cancer (2023). Since 2005, she consistently has been listed among the top doctors by the Castle Connolly report.

From her deep roots in Ireland, which gave her the solid foundation on which she has built an accomplished career in the United States, Dr O’Reilly continues to increase her reach. In partnership with her husband, Ghassan Abou-Alfa, MD, a Lebanese-born medical oncologist at MSK Cancer Center with a faculty appointment at Trinity College in Dublin, she regularly returns to their respective homes, where she is fully aware and appreciative of the different ways in which medicine is practiced in different parts of the world. She underscores the importance of recognizing these differences and not elevating one approach over another but rather cultivating a cultural sensitivity and awareness of these differences.

What does not change by geography or culture is the mandate to keep the patient at the center of all that she does. “At the end of the day, the most important thing in life is the person in front of us,” she says. “For all of us in medicine, it is this really ground-level setting and something we have to be extraordinarily respectful of.”