Often diagnosed in an advanced stage, pancreatic adenocarcinoma is a tumor with a poor and severe prognosis that affects 14,500 people a year in Italy. Recently authorized for reimbursement by the Medicines Agency (Aifa), pegylated liposomal irinotecan (Nal-Iri) based on nanotechnology represents, for patients with pancreatic cancer in the metastatic phase – reports Servier in a note – the first and only drug approved for second-line treatment that guarantees a continuum of care with significant advantages in terms of survival.
Pancreatic cancer, symptoms
“Pancreatic cancer is very insidious in its clinical manifestation, since the symptoms are often atypical, nonspecific and common to very frequent pathologies – explains Michele Reni, director of the Strategic Clinical Coordination Program, Pancreas center, Irccs S. Raffaele hospital, Milan – For a correct and timely diagnosis it is essential to contact a specialized centre, such as the Pancreas Unit, with a predefined and integrated diagnostic-therapeutic care path, competent staff and high volumes of treatment. In our country there are currently not many centers that can offer this 360-degree patient management.”
One of the most difficult tumors to diagnose and with the poorest prognosis with a 5-year survival of 11% in men and 12% in women, pancreatic cancer consists of approximately 15 thousand new diagnoses per year (2022 data) of which, over approximately half, in the metastatic phase. It is the only tumor of the gastrointestinal tract that has not seen improvements in terms of survival in forty years. This neoplasm has a strong unmet medical need due to an often late diagnosis, the biological complexity, the few therapeutic options available and the high specialization required for correct and effective management, diagnosis and treatment. Metastatic forms are considered the most difficult to treat, since the tumor is characterized by a dense stromal layer, which can hinder the penetration of drugs.
Precisely for patients with this tumor in an advanced stage, pegylated liposomal irinotecan (Nal-Iri) is now available in Italy, the first and only drug approved as a second-line treatment for pancreatic cancer. Recognized with orphan drug status, this therapy, developed to maximize its anti-tumor efficacy, is based on liposomal nanotechnology, i.e. on lipid vesicles (liposomes) which contain the active ingredient (irinotecan) and which accumulate preferentially in the tumor tissue. Here the macrophages absorb the liposomes, releasing the irinotecan, which moves into the nucleus of the tumor cells, blocking their replication. This formulation not only improves the biodistribution of the active ingredient but also the stability and pharmacokinetics.
“Due to the poor vascularization – specifies Romano Danesi, full professor of Pharmacology, department of Oncology and Hemato-Oncology, University of Milan – this neoplasm is characterized by the limited quantity of drug that manages to reach the tumor cells that develop in the pancreas. To circumvent this limitation Nal-Iri exploits liposomal nanoparticle technology and thanks to its structural characteristics it favors an improvement and increase in the distribution of the drug within the tumor tissues”.
The clinical efficacy of Nal-Iri in combination with 5-fluorouracil and leucovorin was demonstrated in the global pivotal phase 3 Napoli-1 study. The study documented a statistically significant improvement in median survival from 4.2 to 6.1 months, with a 33% reduction in the risk of death. “The results of Napoli-1 – comments Michele Milella, professor of Oncology and director of the Division of Medical Oncology of the Integrated University Hospital of Verona – have demonstrated an advantage both in terms of objective responses, time to progression and overall survival in the group treated with the combination of the two drugs. Nal-Iri represents the reference scheme for the second line of therapy, thanks to greater tolerability, more solid efficacy and an advantage in terms of both survival and quality of life”.
Based on the results of the Napoli 3 study, on February 13, 2024 the American FDA (food and drug administration) approved Nal-Iri also as a first-line treatment. Confirmations on the advantages of the treatment were also highlighted in a Real World Evidence study in which data relating to treatment with Nal-Iri were collected on patients treated in 11 oncology centers located throughout the national territory. “The data collected demonstrated a reduction in the disease in 12% of patients treated with Nal-Iri – underlines Sara Lonardi, director of Ff Oncology 3, Veneto Oncological Institute – a figure that is certainly not negligible for this type of neoplasm” given that it can be stop “progression for a period in 41% of patients”. In addition to having “finally something new for the treatment of this type of tumor. Delaying the progression of the disease also means delaying the onset of new symptoms, especially pain and weight loss.”
Being able to give 'extra time' to patients with pancreatic cancer has enormous value. “Patients affected by this tumor and their caregivers – recalls Francesco De Lorenzo, president of Favo, Federation of voluntary oncology associations – often find themselves having to face numerous difficulties both in the management of the pathology and the treatment. Added to this are late diagnoses, regional differences in care, deficiencies in psychological, nutritional and rehabilitative support. This makes an integrated and multidisciplinary approach necessary with dedicated PDTAs within specialized centers connected to oncology networks capable of ensuring overall patient care and improved QoL, whatever the stage at which the disease is diagnosed”.
As the Medical Affairs director of the Servier Group in Italy, Marie-Georges Besse, concludes: “Servier has made the fight against cancer one of its priorities and is currently the only company with a portfolio that offers therapies for the advanced stages of major tumors of the gastrointestinal tract: stomach, colon, pancreas and in the future also cholangiocarcinoma, tumors which in Italy affect around 80 thousand people every year. Our commitment in terms of research and development is concentrated on rare and difficult to treat tumors, to offer everyone patients the possibility of taking advantage of subsequent lines of treatment and a continuum of care that respects their quality of life”.
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