The Italian drug agency (Aifa) has approved the first cancer therapy that will be prescribed based on the presence of a mutation, and not based on the type of tumor. The drug in question is larotrectinib, for patients who have a mutation called NTRK fusion. The green light comes two years after the European approval: now even Italian patients with advanced tumors who do not respond to other therapies and who present the NTRK fusion will have an important possibility of additional treatment.
Approved the first anticancer drug without organ indication
What is NTKR merger
The fusion of NTRK (neurotrophic receptor tyrosine kinase) genes with other genes is a genetic abnormality that causes the production of a defective protein (called the TRK fusion protein). When the altered TRK protein becomes active or overexpressed, it fuels the growth and spread of tumors, regardless of where they originated.
The cure becomes (also) “agnostic”
The choice of the most suitable treatment on the basis of molecular characteristics (the mutation) instead of the affected organ is probably one of the greatest innovations of the last 10 years in the world of oncology and represents a cultural revolution. “The therapies commonly used for the treatment of patients with tumors characterized by NTRK gene fusion, such as chemotherapy or immunotherapy, have not always proved effective”, underlines Saverio Cinieri, Director of Medical Oncology and Breast Unit of the ‘Perrino’ Hospital. of Brindisi and President-elect Aiom (Italian Association of Medical Oncology): “Larotrectinib, first in the class of oral TRK inhibitors, showed rapid responses, with a significant and lasting clinical benefit over time, regardless of the patient’s age and location of the tumor “.
Clinical studies conducted on this “agnostic” therapy show important results, especially for pediatric patients, where the best results have been observed. They involved both adults and children already very pre-treated: the new drug obtained a rapid and lasting global response in 75% of cases, with a significant improvement in the quality of life. Studies have shown efficacy in primary central nervous system tumors, as well as in patients with brain metastases, of different age and tumor histologies. Patients presented, for example, lung, thyroid, melanoma, gastrointestinal stromal tumors, colon cancer, soft tissue sarcomas, salivary gland tumors, and childhood fibrosarcomas.
Pediatric oncology becomes more and more “precise”
Who is the new drug for
Let’s say clearly, however, that this is not a panacea for all patients. “There are essentially three situations in which we can go to seek the merger of NTRK”, explains Carmine Pinto, Director of Medical Oncology Comprehensive Cancer Center AUSL-IRCCS of Reggio Emilia and President of FICOG (Federation of Italian Cooperative Oncology Groups): “When we find ourselves in the face of very rare tumors, such as infantile fibrosarcoma or congenital mesoblastic nephroma or secretory breast carcinoma, where there is an 80-90% chance of finding this molecular alteration: in these patients it must be sought by default. Then we have a series of tumors in which the fusion of NTRK must be sought together with other alterations for which we already have targeted drugs. I am referring, for example, to lung adenocarcinoma or colorectal cancer with high microsatellite instability (another molecular feature), because we know that even in these cases there is a high probability of finding it. Finally, there are other situations in which it is necessary to evaluate patient by patient if there is a possibility, even a low one, of finding this mutation. We must not make the mistake of thinking that it can be useful for everyone: it would be giving illusion to patients on the one hand, and a useless waste of resources on the other ”. For this AIOM is working together with other scientific societies and has published the ‘Recommendations on Agnostic Drugs’.
Lung cancer, new confirmations for “agnostic” therapy
And larotrectinib was given
Updated data on larotrectinib were presented at the latest American Congress of Medical Oncology (ASCO). They come from three studies involving a total of 206 adult and pediatric patients with NTRK fusion tumors in over 20 organs. An overall response rate of 75% was observed in these patients, with 22% complete responses. The median duration of tumor responses was over 4 years (49.3 months) and 77% of patients were still alive at 3 years. “All this with excellent tolerability – continues Pinto:” These results have a relevant clinical significance, also because most of the patients presented an advanced state of disease and had already undergone previous therapies “.
ASCO 2021
Tumors with NTRK fusion: the “wild card” drug effective for more than 4 years
Ensure the appropriateness of the tests and the ability to perform them
It will now be essential to guarantee the centers the possibility of taking the tests to identify the merger of NTRK through funding to this. And, nevertheless, ensure that they are done appropriately: “The results of these studies represent a clear rationale for subjecting cancer patients to a comprehensive genomic test that includes the search for fusions of NTRK genes, to better understand what the tumor ‘driver’ gene and associate it with the right treatment ”, explains Anna Sapino of the University of Turin and president of the Italian Society of Pathological Anatomy and Diagnostic Cytopathology (SIAPEC-IAP).
Tumors: 17 thousand tests every year for molecular alterations, but 80% in the Center-North
by Irma D’Aria
The scientific society has created a real national network of high-tech laboratories. “The scientific society has 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 analyzes ”, continues Antonio Marchetti, full professor of pathological anatomy at the University of Chieti and coordinator of the Italian Group of Molecular Pathology and Predictive Medicine (SIAPEC-IAP).
Gastrointestinal tumors, new efficacy data for targeted therapy
“We welcome AIFA’s decision with great satisfaction – concludes Marius Moscovici, Head of Medical Affairs Oncology at Bayer:” The approval of larotrectinib represents a significant step forward in the fight against cancer that is facing a paradigm shift and, as the new era of precision cancer treatment, we continue our effort to provide innovative drugs, which can be of great value for patients and doctors ”.
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