Green light from the Italian Medicines Agency to the first anticancer with agnostic indication that opens a new way of treating certain neoplasms: not based on the organ where they originate, but on a common genetic mutation
It affects 29 different types of cancer regardless of where they are located. It is a “wild card” drug that experts define as “agnostic” because it does not “know” the organ where the tumor originated, but interferes with a precise genetic mutation which can, in fact, be common to many types of neoplasms. The medicine is called larotrectinib and has just obtained the green light from the Italian Medicines Agency (Aifa), the first antitumor with agnostic indication, for the treatment of neoplasms characterized by fusion of NTRK genes (Neurotrophic Tyrosine Receptor Kinase). The three pivotal studies involved adult and pediatric patients with malignancies characterized by NTRK gene fusion, independent of the organ affected by the disease, and showed a rapid and lasting improvement in tumor response and quality of life, with a high overall response rate. , equal to 75 per cent of the patients treated
Precision oncology
“From today, doctors in our country have the opportunity to combine the therapeutic approach based on the tumor histotype with a precision oncological therapy guided exclusively by molecular alteration – he says. Saverio Cinieri, director of the Medical Oncology and Breast Unit of the Perrino Hospital in Brindisi and elected president of the Italian Association of Medical Oncology (Aiom) -. Agnostic approval changes the prospects for treatment and is the first step in a “cultural” revolution. The starting point is no longer represented by the location of the tumor, that is, the organ from which the disease originates, according to the histological model. Agnostic approval leads to the affirmation of the mutational model which is based on genomic profiling and on the identification of molecular alterations regardless of the site of origin of the disease. We are facing the most advanced frontier of precision oncology. To testify the importance of this approach, Aiom has published the “Recommendations on agnostic drugs”, edited by Antonio Russo, member of the board of the scientific society. The therapies commonly used for the treatment of patients with tumors characterized by NTRK gene fusion – continues Cinieri -, such as chemotherapy or immunotherapy, have not always proved effective. Larotrectinib, first in the class of oral TRK inhibitors, showed rapid responses, with a significant and long-lasting clinical benefit, regardless of the patient’s age and location of the tumor “.
New tests to be performed when a tumor is discovered
However, the arrival of the “agnostics” also means changing the approach to diagnosis: we progressively move from the biological profile to the “target drugs”, which is why Molecular Tumor Boards are needed. Knowing the DNA mutations present in a patient’s neoplasm is fundamental today to identify specific alterations that can guide therapeutic choices: target therapy, in fact, they can only be used if the presence of specific markers. Specifically, the tests to be performed are established on the basis of the type of cancer in question (breast, lung, colon and so on). And the techniques used to perform these analyzes are numerous, complex and very sophisticated: they range from immunohistochemistry to immuno-phenomena-typing, from in situ hybridization to cytogenetics, from Sanger sequencing methods to mass spectrometry and next generation sequencing (NGS).
The data of the last American congress of oncology
The Ema (European Medicines Agency), in the annual report “Human medicine highlights 2019”, has included larotrectinib (the only cancer therapy selected) in the list of drugs that have made an important contribution to improving public health, because represents a significant advance in oncology. “The recognition comes from the important results obtained in the studies, which confirm both the short and long-term clinical advantages of the drug – he explains Carmine Pinto, director of medical oncology at the Comprehensive Cancer Center AUSL-IRCCS in Reggio Emilia and president of the Federation of Italian cooperative oncology groups (Ficog) -. Larotrectinib is a drug that has shown high clinical activity not in relation to a single site or histological type of tumor, but based on the presence of a specific molecular alteration, the NTRK gene fusion. This is demonstrated by the updated data presented at the last American congress of medical oncology Asco, coming from three studies on 206 adult and pediatric patients with tumors with NTRK fusion, in over 20 different types of cancer. In these patients it was observed an overall response rate of 75%, with 22% complete responses. The median duration of tumor responses was over 4 years (49.3 months) e at 3 years, 77% of patients were still alive. All this with excellent tolerability. These data have a relevant clinical significance, also because most of the patients presented an advanced state of disease and had already undergone previous therapies “.
Effective in different types of cancer and already metastatic patients
Larotrectinib has been studied in clinical trials in various types of solid tumors, including those of lung, thyroid, gastrointestinal stromal, colon, salivary glands, soft tissue sarcomas, melanoma and childhood fibrosarcoma. It has shown efficacy in primary tumors of the central nervous system, as well as in patients with brain metastases, of different age and tumor histologies. “The results of these studies represent a clear rationale for referring cancer patients to a comprehensive genomic test that includes the search for fusions of NTRK genes, to better understand which is the “driver” gene of the tumor and associate it with the right treatment – he explains Anna Sabino, director of the Department of Medical Sciences at the University of Turin and president of SIAPEC-IAP, Italian Society of Pathological Anatomy and Diagnostic Cytopathology) -. Tumors with NTRK fusion occur when one NTRK gene fuses with another unrelated gene, producing an altered TRK protein, which becomes active or overexpressed, fueling the growth and spread of the tumor, regardless of where it originated ». “Patients candidates for treatment with agnostic drugs must be selected on the basis of the presence of molecular alterations, through specific diagnostic tests – he continues Antonio Marchetti, Professor of Pathological Anatomy of the University of Chieti and coordinator of the Italian Group of Molecular Pathology and Predictive Medicine SIAPEC-IAP -. In this sense, SIAPEC has created a real one National network of high-tech laboratories. The scientific society also promoted the “Progetto Vita”, a study involving 18 Italian centers with the aim of highlighting rare DNA alterations (including fusions of NTRK genes), using a new technological approach, applied for the first time in Italy, to reduce the time and costs of the analyzes ».
Increase Molecular Tumor Boards in Italy
In short, to make the new precision oncology model effective, the Molecular Tumor Boards must be made operational throughout the national territory, i.e. multidisciplinary teams, indispensable for interpreting the results of molecular tests and choosing the best therapy. They are groups formed by medical oncologist, anatomopathologist, molecular biologist, geneticist, clinical pharmacologist, hospital pharmacist, bioinformatician, clinical epidemiologist, bioethicist and patient representatives, who see integrated multiple skills to govern the clinical and decision-making processes of appropriateness. Today, however, only a dozen Molecular Tumor Boards are active in Italy: they must be implemented, to reach about 30, following common criteria in the various centers.
September 9, 2021 (change September 9, 2021 | 20:24)
© Time.News