Professor Michele Reni, Head of the Oncology and Oncology Day Hospital Units, Director of the Strategic Clinical Coordination Program of the Pancreas Center at IRCCS Ospedale San Raffaele, and Associate Professor of Oncology at Vita-Salute San Raffaele University, who conceived and coordinated the study, just presented the results of the CASSANDRA Project at the annual meeting of the American Society of Clinical Oncology (ASCO), the world’s most important oncology conference, held in Chicago.

The study, designed to improve treatment outcomes in patients eligible for surgical resection of pancreatic ductal adenocarcinoma, compared the efficacy of two chemotherapy regimens administered before surgery. The data showed that patients treated with PAXG—a chemotherapy combination developed at San Raffaele in 2012 and authorized by the Italian Medicines Agency (AIFA) in January 2020 for use in patients with metastatic or advanced pancreatic cancer—experienced longer event-free survival than that experienced by patients treated with mFOLFIRINOX, the current standard treatment.

Pancreatic Ductal Adenocarcinoma (PDAC)

The most common type of malignant pancreatic tumor is pancreatic ductal adenocarcinoma (PDAC), accounting for 95% of all malignant pancreatic neoplasms. It represents approximately 3% of all new cancer diagnoses annually, it is the third leading cause of cancer death and it has the lowest 5-year survival rate among solid tumors. The disease originates from the exocrine cells of the pancreas, which produce digestive enzymes, and spreads rapidly to other organs, forming metastases. It is often diagnosed at an advanced stage, and only 10–20% of patients are eligible for surgery. However, over 90% of patients with apparently localized disease already harbor microscopic metastases that are undetectable by current diagnostic tools. For this reason, perioperative chemotherapy has become essential to achieve higher cure rates and prolong survival, as postoperative chemotherapy is often hindered by the slow and difficult clinical recovery after major surgery.

 

The Study – The CASSANDRA Project

“The CASSANDRA study stemmed from the need to improve patient prognosis without compromising  their quality of life as opposed to the standard od care,” says Professor Michele Reni.
The aim of the study was to investigate whether the PAXG regimen leads to improved outcomes as compared to themFOLFIRINOX regimen when administered for 4 or 6 months before surgery. During the study, conducted across 17 Italian hospitals and coordinated by IRCCS Ospedale San Raffaele, 260 patients were enrolled and randomly assigned to two groups: 132 received PAXG chemotherapy, while 128 received mFOLFIRINOX.

The results demonstrated that event-free survival (defined as the absence of progression, recurrence, inoperability, progressive marker increase, intraoperative metastases, or death) was significantly longer in patients treated with PAXG than in those who received mFOLFIRINOX.
“This marks a historic step forward in the fight against pancreatic cancer,” continues Professor Reni, “because of the magnitude of the difference observed when compared to what many have considered until now the most effective treatment for this disease. Furthermore, PAXG-treated patients showed a significantly higher rate of pathological, that is, the amount of residual tumor observed by the pathologist in the tissues removed after therapy, and biochemical responses, as well as a greater likelihood of preventing disease progression during chemotherapy,” explains Professor Reni.
“These results highlight the importance of independent clinical research and demonstrate how innovative treatment strategies can significantly improve patients’ life expectancy, paving the way for a possible update of the treatment guidelines for this cancer,” adds Professor

Massimo Falconi, Head of the Pancreatic Surgery Unit, Director of the Pancreas Translational & Clinical Research Center at IRCCS Ospedale San Raffaele, Full Professor of Surgery at Vita-Salute San Raffaele University, and co-principal investigator of the study.

 

The Crucial Role of Patient Associations

One of the most extraordinary aspects of the CASSANDRA study is that it was entirely funded by five patient associations: My Everest, Codice Viola, Associazione per la Vita, Natalucci, and Oltre la Ricerca. This highlights the crucial role these organizations—and citizens themselves—can play in advancing scientific research.
“Without their support, this study would not have been possible,” emphasizes Professor Reni. “This shows how collaboration between the scientific community and civil society can lead to tangible results in the fight against cancer. We are deeply grateful to the patient associations who believed in our ideas and enabled us to carry out this work. Their commitment and trust were essential in helping us make progress in the treatment of pancreatic cancer, a disease for which many answers are still needed. This study proves that independent research, supported by the community, can truly make a difference.”

 

Future Perspectives, the Role of the Pancreas Center and the Comprehensive Cancer Center

ASCO’s interest in the CASSANDRA study results is a significant acknowledgment of the value of Italian research and of the potential international impact of this new therapeutic strategy. The data presented open new perspectives on the treatment of pancreatic cancer, laying the foundation for potential updates of global guidelines and the launch of further clinical trials.

In this context, the Pancreas Center at IRCCS Ospedale San Raffaele, which enrolled nearly 50% of the study’s patients, confirms its position as a national and international reference center for the diagnosis and treatment of pancreatic diseases. This is thanks to its integrated model involving specialists in oncology, surgery, radiology, gastroenterology, radiotherapy, pathology, nuclear medicine, clinical nutrition, psychology, diabetology, and translational research.

 

The Center stands as a hub of excellence and clinical innovation, closely integrated with San Raffaele’s

Comprehensive Cancer Center directed by Professor Fabio Ciceri, Head of the Hematology and Bone Marrow Transplantation Unit at IRCCS Ospedale San Raffaele and Full Professor of Hematology at Vita-Salute San Raffaele University. It benefits from multidisciplinary collaboration and shared resources, with the goal of developing increasingly effective and personalized treatment strategies to improve both survival and quality of life for patients. “The well-being of our patients is our top priority. The Comprehensive Cancer Center of Ospedale San Raffaele was created to optimize the care and management processes for oncology patients, promoting synergies among all our clinical and scientific Centers of Excellence, including the Pancreas Center. Through the integration of clinical and translational research, we offer innovative, experimental, and personalized treatments to support patients at every stage of their journey,” declares Professor Fabio Ciceri.

Meanwhile, research continues: upcoming results may further refine the therapeutic approach.
“Our work as a Center of Excellence for the treatment of pancreatic cancer does not end here. We will soon release the results of the CASSANDRA study regarding the optimal duration of preoperative chemotherapy—whether it is preferable to administer all 6 months before surgery, or 4 months before and 2 afterward,” conclude Professor Michele Reni and Professor Massimo Falconi.

 

Published on: 03 June 2025