Liver tumors, green light for immunotherapy for the two most frequent forms

Liver tumors, green light for immunotherapy for the two most frequent forms


Immunotherapy changes the treatment of the advanced stages of the two most frequent liver tumors. We are talking about hepatocellular carcinoma and cholangiocarcinoma (which derives from the cells of the biliary tract, the channels that transport bile from the liver to the intestine), for which the Italian Medicines Agency has recently approved the use of durvalumab since the first treatment line.

Specifically, advanced or unresectable hepatocellular carcinoma can be treated with a single initial dose of tremelimumab followed by durvalumab monotherapy; unresectable or metastatic cholangiocarcinoma, however, can be treated with durvalumab in combination with chemotherapy (gemcitabine plus cisplatin).

The Phase III studies HIMALAYA (published in Annals of Oncology) and TOPAZ-1 (published in the New England Journal of Medicine Evidence) demonstrated the benefit of the immunotherapy drug, respectively. In the first, a quarter of HCC patients treated with durvalumab plus tremelimumab were alive at 4 years compared to 15% of those treated with sorafenib (standard of care at the start of the study) and the risk of death was reduced by 22%. %. In the second, durvalumab plus chemotherapy reduced the risk of death by 24% compared to chemotherapy alone in patients with cholangiocarcinoma, with an estimate of patients still alive two years after the start of treatment more than doubled (23.6% compared to 11.5%).

In 2023, in Italy, an estimated 12,200 new diagnoses of liver cancer were estimated, of which 79% were represented by hepatocellular carcinoma. “Both in the world and in Italy it is one of the main causes of death from cancer, particularly in men between 60 and 70 years old. In the large majority of cases, the tumor develops in patients suffering from chronic liver disease, often already at the cirrhosis stage, linked above all to hepatitis B and C virus infections, alcohol abuse, genetic and autoimmune diseases, but also to metabolic syndrome. Both cirrhosis and liver cancer often arise silently: “Only the identification of people at risk, i.e. with advanced chronic liver disease who do not yet present any symptoms, and their careful surveillance with six-monthly ultrasound scans allow an early diagnosis of the neoplasm, i.e. in an initial phase in which it is possible to intervene with radical therapies, such as surgery, transplant or percutaneous ablation – explains Fabio Piscaglia, Professor of Internal Medicine at the University of Bologna and Director of Internal Medicine, Hepatobiliary and Immunoallergological Diseases of the IRCCS-AOU of Bologna -. Unfortunately, for various reasons, more than half of patients do not receive this surveillance and, when the disease appears, it is already in an advanced stage. The best management of hepatocellular carcinoma requires the contribution of various specialists and a real therapeutic alliance between the patient and clinicians”.

A boost to the immune system

Precisely because the tumor must be treated without underestimating the underlying liver disease, the treatment is complex: “The management of two serious concomitant pathologies requires effective and tolerable therapies, which do not worsen the residual liver function – underlines Mario Scartozzi, Professor of Medical Oncology of the University of Cagliari – AIFA has approved the reimbursement of the new STRIDE regimen (Single Tremelimumab Regular Interval Durvalumab, ed.), based on two immunotherapy drugs, durvalumab plus tremelimumab, which has shown a significant increase in survival. One in four patients treated with the STRIDE regimen is alive at four years. No other therapeutic regimen has demonstrated these results so far. The response rate was also superior with durvalumab plus tremelimumab. ” STRIDE is based on an innovative ‘immune priming’ approach with a single dose of tremelimumab followed by durvalumab monotherapy. “This single administration of tremelimumab, at a higher dosage than the traditional one, is able to provide a ‘boost’ to the immune response. Furthermore, the quality of life was safeguarded, with a good tolerability profile, which is very important in patients with this type of neoplasm, who tend to be more fragile and characterized by various comorbidities”, specifies the expert.

The therapies available to clinicians are therefore increasing, thus allowing a greater number of patients, for example those with contraindications to antiangiogenic drugs, to receive beneficial pharmacological therapies and to use an innovative approach. “The hope – continues Piscaglia – is to be able to give patients hope of obtaining long-term tumor control. New therapies are also opening up important perspectives thanks to the combination of pharmacological therapy with the treatments already provided for the various stages of the disease”.

“For patients with advanced disease, not eligible for surgery and locoregional therapies, it is essential to have access to effective tools such as immunotherapy – states Massimiliano Conforti, vice president of EpaC -. It is also important to raise awareness among family doctors, to activate surveillance programs for people at risk with advanced liver disease, but also to inform patients with liver cancer about the reference structures, which guarantee 360-degree care. Early diagnosis and rapid treatment paths, within regional hepatology networks, are the key to gaining years of life, in addition to innovation consisting of increasingly effective therapies”.

Biliary tract cancer

A rare but constantly growing pathology. It is cancer of the biliary tract, which records around 5,400 new cases in Italy every year, 70% of which are diagnosed at an advanced stage. For these patients, the first choice treatment to date has been chemotherapy, which helps to control the evolution of the tumor, although with limited effectiveness. “The TOPAZ-1 study – states Lorenza Rimassa, Associate Professor of Medical Oncology at Humanitas University and IRCCS Humanitas Research Hospital in Rozzano, Milan – involved 685 patients and demonstrated that durvalumab in combination with chemotherapy is able to improve the survival in first-line treatment. The combination also showed a reduction in the risk of progression and a better response rate, without altering the quality of life compared to chemotherapy alone. After more than a decade of waiting for new treatment options, this immunotherapy-based regimen changes the standard of care on the front lines.”

“The approval of the reimbursement of durvalumab by AIFA for the treatment of biliary tract tumors is very important news – states Paolo Leonardi, President of the Association of Italian Cholangiocarcinoma Patients (APIC) – because it prolongs life by controlling the development of the tumor . A second important step after the first targeted drugs, which we hope will also all be made available to people diagnosed with cholangiocarcinoma. I hope these treatments will spread even if it remains important, when setting up the therapy, to resort to specialized structures, where complete management by a dedicated multidisciplinary team is possible. Simultaneous care makes the difference for these patients, as well as taking into account the psychological, nutritional, pain therapy and rehabilitation aspects.”

Stomach cancer

Immunotherapy is also showing important results in stomach cancer. “In the MATTERHORN study, in operable gastric or gastro-esophageal junction cancer – continues Scartozzi -, the addition of durvalumab to the FLOT chemotherapy regimen, before and after surgery, highlighted a significant increase in the pathological response rate compared to only FLOT: 19% versus 7%, with a difference between the two treatments of 12%. It is particularly encouraging to see the safety of the combination of durvalumab plus chemotherapy, which did not compromise the ability to undergo surgery. The results of this study were highly anticipated, because in patients with gastric or gastro-esophageal junction tumors undergoing surgical resection after treatment with chemotherapy the recurrence rate is currently still 50%.”



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