A single drug, developed by Italian researchers, which at the same time is both “wild card” – that is, for all tumors that have the NTRK mutation, regardless of the organ affected – is highly specific for lung tumors with ROS-1 mutation . This is entrectinib, which has just received the green light from the Italian Medicines Agency (Aifa) for both indications.
Innovation made in Italy
Entrectinib is an Italian-speaking molecule. In fact, the research started in the Nerviano Medical Sciences laboratories and continued in the clinical development phases at the Niguarda Cancer Center and at the National Cancer Institute in Milan. It is a so-called agnostic drug: it can be prescribed not on the basis of the tumor site, but on the presence of a particular mutation, the fusion of the NTRK genes. This alteration in fact produces a “defective” protein that underlies the development and growth of cancer. E that represents the target of entrectinib. The authorization covers all adult and pediatric (over 12 years) patients with solid tumors. In most cases, these are rare cancers, which do not respond to other treatments. Treatment has been shown to be effective in patients with sarcoma, non-small cell lung cancer, mammary analogue secretory carcinoma (MASC), salivary gland, secretory and non-secretory breast cancer, thyroid cancer, colorectal cancer, neuroendocrine, pancreatic, ovarian tumors, endometrial carcinoma, cholangiocarcinoma, gastrointestinal tumors, neuroblastoma and other solid tumors.
Lung cancer, it’s time for personalized and agnostic therapies
But entrectinib also targets the fusion of ROS1, another gene that plays an important role in controlling cell growth and proliferation. When this genetic alteration occurs, cancer cells grow and proliferate uncontrollably, and blocking this abnormal signaling can result in cancer cell death. Aifa’s approval is for adults with ROS1-positive advanced non-small cell lung cancer (NSCLC) who have not previously been treated with ROS1 inhibitors.
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“The approval of entrectinib as an antitumor therapy with agnostic indication confirms the innovativeness of this therapeutic option for the effective treatment of patients with solid tumors characterized by alterations of the NTRK or ROS1 genes,” he says. Filippo de Braud, Professor of Oncology at the University of Milan and Director of the Department of Medical Oncology and Hematology of the IRCCS National Cancer Institute Foundation: “The value of this target therapy is amply demonstrated by the evidence gathered in clinical trials: high response rates, duration of response extensive and good tolerability profile. Furthermore, thanks to the fact that the drug penetrates the blood brain barrier, good rates of intracranial response are obtained, higher than 50% in the presence of brain metastases at baseline “.
A new paradigm
The tumor, therefore, is no longer identified through the affected organ, but (also) through the “driver” mutation that guides its growth: a cultural change that represents a revolution in the world of oncology. “The fact that entrectinib is designated as an ‘agnostic’ anti-cancer therapy – that is, regardless of tumor type – and is now approved in Italy fills us with pride,” he adds. Salvatore Siena, Professor of Medical Oncology at the University of Milan and Director of the Oncology Department of the Niguarda Hospital in Milan: “The goals achieved at the clinical and regulatory level by this” made in Italy “molecule are also an expression of the quality of Italian scientific research and the strong drive for innovation in our country, as well as being a fundamental result in the field of personalized medicine, which is expanding the prospects for treatment for thousands of cancer patients “.
How access to the drug is established
There is another innovation, which concerns access to the drug. A central element of the new organizational model is? represented by multidisciplinary groups, which will deal with the interpretation of the genomic profile of a tumor for the recommendation of the most? appropriate for the patient, based on specific alterations detected with latest generation tests for broad genomic profiling, such as NGS (Next Generation Sequencing) technology.
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“The versatility of entrectinib, even in light of its recent approval, can truly revolutionize treatment prospects for patients with ROS1-positive advanced non-small cell lung cancer and for patients with NTRK-positive tumors,” he comments. Silvia Novello, Professor of Medical Oncology at the University of Turin and President of WALCE Onlus (Women Against Lung Cancer in Europe): “Its marked effectiveness allows it to be active at the level of the central nervous system, often the site of metastases that are difficult to treat, offering cancer patients new treatment options and an improvement in life expectancy ”.
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The findings in lung cancer
The results of clinical studies show a response in about 70% of patients with ROS1-positive NSCLC lung cancer, of which 35% had brain metastases, also highlighting a good profile of tolerability and handling, fundamental aspects both for clinicians and for patients who can benefit from this oral therapy. “For the correct use of this, as well as of the other targeted drugs, it is essential to identify the targets of action – concludes Novello – by carrying out genomic profiling tests that identify the mutations and genetic alterations on which to direct the most appropriate treatment”.
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