Cassandra study: new protocol for the treatment of pancreatic adenocarcinoma

Adenocarcinoma of the pancreas has recently returned to the centre of media attention, not only because it has affected ordinary people and well-known figures, but also because of the frequent - and sometimes premature - announcements of alleged therapeutic advances that are not always reflected in clinical practice. It is a pathology that, despite the numerous efforts of the international scientific community, continues to represent one of the most complex challenges in oncology, both because of the difficulty of early diagnosis and because of the limited therapeutic options that are truly effective.
It is in this context that the Cassandra study, an independent trial, fits in, representing one of the most solid and relevant results of recent years, helping to focus attention on concrete and clinically significant evidence, beyond the media hype.
Professor Michele Reni, creator and coordinator of the study, head of the medical oncology and oncology day hospital operating units and director of the strategic clinical coordination programme of the Pancreas Centre at the IRCCS San Raffaele Hospital in Milan, speaks about it.

Pancreatic adenocarcinoma: a complex pathology
Pancreatic adenocarcinoma is a relatively rare disease, characterised by an extremely severe clinical impact. In most cases it is diagnosed at an advanced stage, when the possibilities for curative intervention are already limited, resulting in rapid disease progression and an often poor prognosis.
"The numerous and disabling symptoms, including pain, weight loss, jaundice and fatigue, profoundly impair patients' quality of life and make clinical management particularly complex, especially in centres with less experience or lacking an adequate multidisciplinary approach," explains Prof. Reni.
In the last thirty years, therapeutic advances have been few and, in most cases, the result of academic research, which, however, has limited resources. "In some cases, the support of the pharmaceutical industry, while important, can influence choices and limit the innovative impetus, directing research towards more conservative strategies," adds the specialist.

The Cassandra study
In this scenario, the Cassandra study, the first randomised Phase 3 trial entirely financed by patient associations, MyEverest and Codice Viola, is set. "This already represents an extraordinary achievement, because it has guaranteed full independence to researchers and strengthened the principle of the doctor-patient alliance. The direct involvement of the associations has contributed to defining priorities that are more in line with real needs," says the specialist.
Sponsored by the Italian Association for the Study of the Pancreas (AISP) and coordinated by the IRCCS Ospedale San Raffaele, the study involved 260 patients, enrolled quickly during the covid-19 pandemic, a result made possible thanks to the collaboration of 17 Italian centres, testifying to an increasingly cohesive and organised research network.
The objective of the study was twofold: to compare the efficacy of the PAXG and mFOLFIRINOX chemotherapy regimens in preoperative treatment and to evaluate the impact of therapy duration. The therapy lasted 6 months in both groups: in one case, all 6 months were administered before surgery, in the second case 4 before and 2 after surgery.
"The results demonstrated the clear superiority of PAXG, a four-drug combination developed in academic circles, over mFOLFIRINOX, which is more toxic and complex to manage. PAXG is therefore proposed as a new therapeutic standard," the professor continued.
Already authorised by Aifa since 2020, the PAXG regimen is now also used in clinical practice in other countries, representing one of the most significant contributions of Italian oncology research at the international level.
The study also showed a reduction of about 40% in the risk of relapse, which is particularly relevant in a disease where relapses are frequent and often early.
No significant differences related to the duration of treatment emerged.

Future perspectives: next studies
The success of Cassandra, both in terms of collaboration with associations and in terms of the clinical results obtained, has encouraged the emergence of new initiatives based on the same model.
The success of Cassandra, both in terms of collaboration and the clinical results obtained, has encouraged new initiatives based on the same model, including the Loch Ness study, currently at an advanced stage of preparation, which aims to further improve therapeutic results through even more personalised and innovative strategies. "The Cassandra study," concludes Reni, "has helped to strengthen and consolidate collaboration between Italian centres active in pancreatic adenocarcinoma research, laying the foundations for accelerating future progress.