Targeted against the alteration of the ALK gene (more common in non-smokers), it is a third generation drug, useful and well tolerated in patients who no longer respond to previous treatments
Lung cancer, of which over 41,000 new cases are diagnosed every year in our country, is still the deadliest cancer in Italy today. More than 70% of patients, indeed, comes to the diagnosis too late because the neoplasm does not show evident signs of its presence until it is now in an advanced stage and is, therefore, unfortunately more difficult to cure and the chances of healing are few. Several therapeutic solutions have been developed in recent years and the survival of the patients has thus lengthened. Now a new drug is added to the armory of specialists with the approval by the Italian Medicines Agency (Aifa) of a drug that is also effective against brain metastases and in patients who have already developed resistance to other treatments.
Drug targeted against the alteration of the ALK gene
The new treatment (lorlatinib) gained reimbursement for i adult patients with advanced non-small cell lung cancer in which there is lalteration of ALK (a rearrangement due to the fusion of two gene fragments) and the disease progressed after therapy with second generation tyrosine kinase inhibitors. The new drug is in fact a third generation tyrosine kinase inhibitor, specifically designed to overcome the blood brain barrier and therefore act at the cerebral level, as well as to be active also in patients previously treated with this class of drugs in which secondary resistance mutations have developed.
“In the last 20 years there have been many scientific achievements and research progresses in the diagnosis and therapy of non-small cell lung cancer with the identification of new action targets and specific drugs – he explains Silvia Novello, Full Professor of Medical Oncology at the Department of Oncology of the University of Turin and president of WALCE (Women Against Lung Cancer in Europe) Onlus -. It is now known that there are different types of cancer that affect the respiratory system and it is based on this information (including any genetic mutations present or not that can direct towards the choice of a drug rather than another) that the procedure is established. treatment more suitable for the single person “.
Knowing the genetic mutations to choose the most effective treatments
From surgery to radiotherapy, passing through chemotherapy and the latest generation treatments such as biological target drugs (more comfortable to take, because in pills) and immunotherapy, today the treatments available are many and are often combined with each other. ALK, EGFR, KRAS, BRAF, ROS seem incomprehensible acronyms, which instead have a decisive value for patients: they are in fact the names of the genes that play a decisive role in this disease and precisely in the presence of these “acronyms” they can be used today new drugs, which opened up hopes that were unimaginable until a few years ago. «Despite this there is still a strong need for solutions, especially to deal effectively with the disease at the time of progression and in particular when it affects the brain – explains Novello -. The availability of lorlatinib is therefore absolutely positive news because it allows us to treat patients with ALK rearrangement, for whom it was urgent to find a solution for an adequate approach to the disease in its course “. The ALK mutation is present in 5-7% of patients with non-small cell lung cancer, with a higher incidence in younger patients (under 50) and mostly, but not exclusively, non-smokers: even in Italy today one out of five cases concerns non-smokers, but if genetics plays a role, 85% of lung cancer cases are due to smoking.
Tumor and metastases regress in half of the patients
In the presence of the ALK alteration, a mutated protein is produced that promotes tumor growth and metastasis of neoplastic cells. The tyrosine kinase inhibitors are a class of drugs capable of blocking the action of the mutated protein, demonstrating efficacy in the treatment of tumors that present this molecular alteration. However, the majority of patients treated with this first generation class of medicines will experience one disease progression due to the development of secondary mutations. The second generation molecules were developed precisely to overcome the problem of resistance, but the neoplasm is able to “bypass” the treatments and progress further, especially at the level of the central nervous system.
«The development of resistance and the progression of the disease in the nervous system central problems remain in the management of the disease despite the clinical benefit derived from the use of second generation tyrosine kinase inhibitors – he points out Cesare Gridelli, director of the Onco-Hematology Department at the Moscati di Avellin hospitalor -. Data for lorlatinib show significant and lasting responses in patients with this malignancy, many of whom had brain metastases and a history of failure to previous tyrosine kinase inhibitor treatments. The drug proved highly effective, making records tumor regressions in approximately 50% of ALK positive patients pretreated “.
A well tolerated cure
The ability to reach the brain allows lorlatinib to act on brain metastases and make them regress. “Unfortunately, about half of these patients develop brain metastases,” he adds Federico Cappuzzo, director of Medical Oncology 2 at the Istituto Nazionale Tumori Regina Elena in Rome -. Having a drug available that has an action on the brain even greater than that exercised in other organs is an element of great importance because very often brain metastases are associated with symptoms and disability which lead to a significant deterioration in the quality of life. The drug also is well tolerated, with generally manageable side effects».
In order to have a better chance of healing, even in lung cancer, early diagnosis is essential: for this we must pay attention to what could be the early symptoms lung cancer, share them with your doctor and, where appropriate, proceed with specialist visits and appropriate tests: unfortunately they are non-specific signals and could be confused with those of other respiratory diseases, but the cough is one of the most frequent, the shortness of breath (dyspnea) o breathlessness, the r
hissing breath of the voice. Equally important would be, for heavy smokers, to perform a control spiral CT scan which allows to identify very initial “silent” carcinomas.
December 2, 2021 (change December 2, 2021 | 13:21)
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