Today there are molecular target-oriented treatments for all major oncological diseases: breast, lung, colorectal, stomach and ovarian cancers, melanoma and gastrointestinal stromal tumors (GIST). Targets that can be discovered thanks to the execution of molecular profiling analyzes with Next Generation Sequencing technology, thus allowing patients to access targeted therapies on the genetic mutation that has been found and thus obtaining a significant clinical benefit. For lung cancer, most of the genetic modifications have been identified in the non-small cell form (NSCLS) and particularly concern oncogenes (those genes that can potentially induce a neoplastic transformation in cells) such as ALK, ROS1 and RET.
A new opportunity
An approach that is bringing the first results. The European Commission recently approved entrectinib, a therapy indicated for the treatment of non-small cell lung cancer (NSCLC) with ROS1 gene rearrangement and for patients with another mutation, that of the NTRK gene. This last indication constitutes one of the first models of agnostic therapy that will be approved in Italy.
“I believe that entrectinib will be another revolution in the treatment of non-small cell lung cancers, also expanding the treatment options for other neoplasms characterized by the NTRK imprint and this is an advantage for cancer patients, who are seeing an increase the possibilities of treatment and their life expectancy. Entrectinib has been shown to be effective in 70% of cases and is a drug characterized by versatility, being in fact active on multiple targets and with local and systemic efficacy, including the central nervous system, one of the often insurmountable limitations of many other targeted drugs. “- said Silvia Novello, Professor of Medical Oncology at the University of Turin and President of WALCE Onlus (Women Against Lung Cancer in Europe – Women against lung cancer in Europe)” – “Having demonstrated the efficacy of therapies such as entrectinib once again underlines the absolute necessity of carrying out genomic tests to identify those patients with gene alterations, so that they can receive in a timely manner a specific treatment directed against the “driver” gene, because only in this way can we really impact on prognosis “.
Drugs under study
Rearrangements (mutations) of the ALK gene have been found in 3-6% of all cases of NSCLC, with a higher frequency in adenocarcinomas, in patients of Asian ethnicity, male, young and non-smoking status or “occasional” smokers (below 10 packs a year). These mutations are considered a new therapeutic target in non-small cell lung cancer and patients with this alteration are treated with specific inhibitors, such as crizotinib, which to date in Italy is used in the second line for the treatment of patients with advanced stage ALK-positive NSCLC.
The ALEX clinical trial, a randomized, open and multicentre Phase III trial, investigates the efficacy and safety of alectinib, a drug capable of blocking the ALK signal in patients with ALK-positive, non-small cell lung cancer (NSCLC). still undergoing treatment, comparing it to crizotinib. The latest study results show that alectinib, as an initial treatment, significantly reduces the risk of disease progression or death by 57% compared to crizotinib. The median time between cure of the tumor and its reappearance is 34.8 months in patients treated with alectinib, more than tripled compared to patients treated with crizotinib, in which this period does not exceed the calendar year (10 ,9 months). Furthermore, treatment with alectinib resulted in an 84% reduction in the risk of neoplastic progression of the central nervous system and protects against the development of brain metastases.