The Italian Medicines Agency (Aifa) has approved the reimbursement of trastuzumab deruxtecan as monotherapy for the treatment of adult patients with advanced Her2-positive (Her2+) adenocarcinoma of the stomach or gastroesophageal junction (Gej), who have received previous treatment at basis of trastuzumab. These patients with advanced disease, who have progressed after first-line anti-Her2 treatment, can now benefit from trastuzumab deruxtecan, a monoclonal antibody drug conjugate from Daiichi Sankyo and AstraZeneca, which can improve both objective response and overall survival.
In December 2022 – the pharmaceutical companies explain in a note – the treatment was approved by the European Commission in this indication, based on the results of the Destiny-Gastric01 and Destiny-Gastric02 studies. It is the first anti-Her2 drug approved in the European Union in over a decade for gastric cancer. “Trastuzumab deruxtecan – states Sara Lonardi, Ff director of Oncology 3 at the Venetian Oncology Institute Irccs in Padua – has proven to be very effective in a complex clinical condition, i.e. in patients with Her2+ gastric carcinoma not amenable to surgery, after failure of the first line of medical therapy consisting of chemotherapy plus trastuzumab. In these cases, until now, the possibilities of treatment were limited. It is an Adc (antibody-drug conjugate) type drug that combines a monoclonal antibody, trastuzumab, with a chemotherapy drug, deruxtecan”.
“In the randomized phase 2 Destiny-Gastric01 study, published in the 'New England Journal of Medicine', conducted on 187 patients from Japan and South Korea”, recalls Lonardi, the treatment “showed important advantages. A objective response rate of 51% in patients treated with trastuzumab deruxtecan compared to 14% with standard therapy. Median progression-free survival was 5.6 months compared to 3.5 months. Median overall survival reached 12, 5 months versus 8.4 months.” These significant results were also confirmed in the Destiny-Gastric02 study, published in 'The Lancet Oncology', which involved 79 patients in North America and Europe. “The Iov of Padua – underlines Lonardi – is one of the centers that has enrolled the most patients. The response to therapies is usually different in the Eastern population compared to the Western one; in the case of trastuzumab deruxtecan, however, the results are similar. In the Destiny-Gastric02 study, all patients received treatment, with an objective response of 42%, a progression-free survival of approximately 6 months, and a median overall survival of more than 12 months.”
In 2023, in Italy – the note reports – approximately 15 thousand new cases of stomach cancer were estimated (9 thousand men and 6 thousand women). Less than 20% are identified at an early stage. In fact, 5-year survival still remains low, equal to 35% in women and 30% in men. “It is an aggressive neoplasm frequently diagnosed in a locally advanced or metastatic stage – explains Carmine Pinto, director of Medical Oncology of the Comprehensive Cancer Centre, Ausl-Irccs of Reggio Emilia – and characterized by a high rate of recurrence even after surgical intervention radical. Until now, these patients had limited therapeutic possibilities after progression on the initial treatment which involves the combination of chemotherapy with an anti-Her2 drug, trastuzumab. Thanks to the reimbursement of Aifa, trastuzumab deruxtecan becomes available in patients with advanced Her2 gastric cancer -positive, already subjected to a previous anti-Her2 treatment. This is an important change in the treatment strategy for the 20% of patients with gastric cancer who have overexpression of Her2”.
Precisely for this reason “it is important to subject all patients with advanced gastric cancer to the diagnostic test to evaluate the expression of Her2 from the beginning of the treatment process – remarks Pinto – with the awareness that this determination is fundamental not only for the first line of therapy, but also for the subsequent one. In these patients with Her2+ gastric cancer, therefore, the therapeutic strategy involves a first line with chemotherapy plus trastuzumab and a second line with trastuzumab deruxtecan. Important advances have recently also been achieved in the therapy of Her2 negative disease , combining chemotherapy with immunotherapy in PD-L1 positive patients. The landscape is really changing.”
“The research – comments Claudia Santangelo, president of Vivere senza stomach (si posto) – makes innovative treatments available to patients such as trastuzumab deruxtecan, which represents a significant step forward in the control of metastatic disease. Gastric cancer is a highly complex pathology clinical and requires dedicated paths for diagnosis, treatment and assistance. Taking care of these patients, particularly with advanced cancer, requires a multidisciplinary approach that allows for global management, improving survival and quality of life. It is very important that patients receive a nutritional assessment right from the start and that they are followed from this point of view throughout the treatment process. People affected by stomach cancer, in fact, risk malnutrition from the early stages of disease. Greater attention to nutritional aspects improves the quality of life and the possibility of accessing multiple lines of therapy with a positive impact on survival”.
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