For years there had been no progress in treatments for cholangiocarcinoma, a rare bile duct tumor that is very difficult to treat. However, things are about to change: the Italian Medicines Agency (Aifa) has in fact approved the reimbursement of pemigatinib for the treatment of adult patients with locally advanced or metastatic cancer, progressing after previous chemotherapy. A targeted therapy, well tolerated, which works by slowing the evolution of those tumors that have a specific mutation, fusion or rearrangement of the fibroblast growth factor receptor 2 (FGFR2).
What is cholangiocarcinoma
Cholangiocarcinoma is a rare cancer that forms in the bile ducts inside the liver (intrahepatic) or outside (extrahepatic). In Europe there are 6-8 thousand cases every year. Unfortunately, most patients are diagnosed when the cancer is advanced and treatment options are very limited. Surgery is often no longer viable and systemic treatments such as chemotherapy do not guarantee a lasting response. The prognosis, therefore, is poor: overall survival 5 years after diagnosis is less than 20%. “In recent years, however, our molecular knowledge on these tumors has grown”, explains Giordano Beretta, Director of the Medical Oncology Unit of ASL breaking latest news and President of the AIOM Foundation. “Today we know which gene mutations drive their growth: about half of intrahepatic cholangiocarcinomas have at least one target mutation that can be targeted with molecularly targeted drugs.”
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Search for mutations
For this reason, in a disease where the therapeutic chances are not high, it is important to obtain a complete profiling of the mutations present as soon as possible, and to do so it is necessary that the centers are organized in an adequate way and that they are spread throughout the territory. Molecular Tumor Board, the task forces capable of evaluating individual cases. “If it is true that today the first line of treatment is chemotherapy for everyone – adds Beretta – starting from the second line the presence or absence of certain mutations can guide the choice of target drugs”.
The first targeted therapy
Specific alterations (fusions or rearrangements) of the fibroblast growth factor receptor 2 (FGFR2) gene are present in 10-16% of intrahepatic cholangiocarcinomas, in particular. These are the target of pemigatinib, which inhibits the activity of mutated FGFR2 and reduces the proliferation of cancer cells. “The results of the Fight-202 clinical trial demonstrated that in patients presenting with fusions or rearrangements of FGFR2, administration of pemigatinib alone resulted in an overall response rate of 37%,” explains Filippo de Braud, Director of the Department of Oncology and Hemato – oncology of the Istituto Nazionale Tumori Milano: “A value which corresponded to a significant and radiologically demonstrated clinical improvement, so much so that the median survival found in these patients was 30 months compared to the 14 months obtained in patients in whom the therapy did not gave answers. Pemigatinib is to date the drug with the best results in terms of activity in this patient population and represents a valid treatment option once the disease has progressed after chemotherapy ”.
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Who is most at risk
The percentage of patients who reach the diagnosis when the disease is now in an advanced stage is high, with negative consequences on the quality of life, and for this reason it is necessary to provide information: “The symptoms – explains Giovanni Brandi, Director of the specialization school in oncology doctor of the IRCCS Policlinico Sant’Orsola of the University of Bologna and founder of APIC (Italian Association of Cholangiocarcinoma Patients) and GICO (Italian Cholangiocarcinoma Group) – often they are not evident in the initial phase, but more risky categories can be identified, such as those is affected by sclerosing cholangitis and primary biliary cirrhosis or hepatic steatosis. “In all these people it would be appropriate to provide periodic checks”.
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The approval of pemiganitib is news that rekindles the hopes of patients, aware of the seriousness of the prognosis. “Once they get to the second line of treatment, patients know that chemotherapy no longer offers great benefits, in the face of important side effects,” concludes Brandi. “It is therefore natural that the news of a drug that represents a real alternative to chemo is very important for them, even if it involves only the limited population of patients who have the target mutation. The hope is that drugs like this can be increasingly developed and made available, so that they can be used not only at a very advanced stage or when the first therapy fails, but from the very beginning. ”