Merck has announced that the Italian Medicines Agency (Aifa) has accepted for reimbursement tepotinib (trade name Tepmetko*), a once-daily oral therapy for the treatment of adult patients with advanced non-small cell lung cancer (NSCLC), with genetic alterations causing epithelial mesenchymal transition factor exon 14 (Metex14) skipping, requiring systemic therapy following prior treatment with platinum-based immunotherapy and/or chemotherapy. With the first approval received in Japan in March 2020, tepotinib was the world’s first oral MET inhibitor to receive regulatory approval for the treatment of advanced NSCLC with Met gene alterations. The drug then received approval for this indication from the US FDA in February 2021 and, a year later, from the European Medicines Agency EMA.
In Italy in 2022 – according to estimates by Aiom, Airtum and the National Screening Observatory – there were 43,900 new diagnoses of lung cancer, the second most frequent neoplasm in men (with a 5-year survival of 16%) and the third in women (with 5-year survival of 23%); the leading cause of cancer death in men and the second in women. Worldwide, NSCLC accounts for approximately 85% of all lung cancers.
In the NSCLC – the note continues – the tyrosine kinase (Tki) inhibitors of the EGFR (epidermal growth factor receptor) and the Alk gene (anaplastic lymphome kinase) have paved the way for a new era of precision oncological medicine. Furthermore, additional oncogenic drivers, such as the Met gene, have recently been identified as specific treatment targets. Mutations in Met signaling pathways occur in 3-4% of NSCLC cases and are associated with a poor prognosis in the case of advanced disease. These patients are typically over 70 years of age and very often have an active or previous history of smoking. Tepotinib has demonstrated marked antitumor activity in adult patients with advanced or metastatic NSCLC.
The efficacy and safety of tepotinib were evaluated in a single-arm, open-label, non-randomized multi-cohort, multicenter clinical study (‘Vision’). Data from the study’s primary analysis were published in the New England Journal of Medicine and showed consistent and durable responses to tepotinib in both treatment-naïve and treatment-experienced adult patients. The primary endpoint was the objective response rate, confirmed by the ‘Recist’ (Response Evaluation Criteria in Solid Tumor) evaluation criteria; additional efficacy measures were duration of response, disease-free survival, and overall survival. In the ‘Vision’ study, patients who received tepotinib for second-line or later-line therapy had an objective response rate of 44.2%, duration of response (DoR ) and disease-free survival (Progression Free Survival), median of 11.1 and 11.0 months, respectively. Additionally, median overall survival was 19.9 months.
“If treated with chemotherapy alone, Nsclc offers an overall survival of about 12 months – declares Filippo de Marinis, director of the Division of Thoracic Oncology of the European Institute of Oncology and President of Aiot (Italian Association of Thoracic Oncology) -. The majority of newly diagnosed NSCLC patients are advanced: the proportion of NSCLC patients with stage IV disease at diagnosis is 47%-55% and 25%-30% with stage III disease at diagnosis. Stage IV, the metastatic stage, is the most difficult to treat – continues de Marinis – however today traditional chemotherapy, which does not significantly reduce the risk of recurrence, is not the only possibility. In recent years, immunotherapy (alone or in combination with chemotherapy) and targeted therapies on altered genes have become fundamental tools in the treatment of metastatic non-small cell lung cancer. Among the drugs with a molecular target, tepotinib allows to design a new targeted therapeutic pathway for patients with METex14 genetic alterations, which are particularly difficult to treat and with a poor prognosis. All this while maximizing the clinical benefit, against a manageable safety profile”.
“The quality of life in patients with Nsclc is highly compromised – adds Silvia Novello, full professor of Medical Oncology, Department of Oncology, University of Turin and president of Walce Women against lung cancer in Europe – both as regards the emotional sphere (depression and anxiety), both as regards the physical functionality of the patients. The impact on quality of life is most unfavorable for patients with advanced or progressive NSCLC and for those receiving subsequent lines of treatment. Tepotinib represents an important opportunity for patients with genetic alterations of METex14, as it allows to optimize the clinical benefit without negative impacts on quality of life”. In order for all patients to have “equal opportunity to promptly access the therapeutic options offered by drugs with a molecular target, such as tepotinib – remarks Novello – a complete molecular profiling at diagnosis is important, to design an optimal therapeutic pathway and allow patients to benefit from the treatments best suited to their condition.
“The introduction of tepotinib into clinical practice in Italy allows us to respond to an urgent unmet therapeutic need – declared Jan Kirsten, President and CEO, Healthcare, Merck Italy – We are therefore pleased to be able to make available to healthcare professionals and their patients a therapeutic solution capable of making an important change in the management of such a serious pathology. In fact, with tepotinib it has been possible to identify a new targeted therapy for lung cancer, adding a new ‘piece’ to the therapeutic armamentarium against one of the most insidious oncological diseases”. “Finding answers to important unmet needs is a commitment that the company has made with its patients and pushes us to continue our commitment to oncological research with passion, in order to be able to offer more and more cutting-edge solutions, capable of improving and significantly prolong people’s lives,” he concludes.
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