Minerva medica
-
The treatment landscape of advanced non-small cell lung cancer (NSCLC) patients has dramatically changed over the past 10 years, particularly thanks to the advent and development of several tyrosine kinase inhibitors (TKI) targeting oncogenic drivers. Among them, patients bearing anaplastic lymphoma kinase (ALK) translocations, which are causative of 3-5% of all advanced NSCLC, have seen dramatically improved their clinical outcomes moving life expectancy at 5 years from less than 5% to 50%. In fact, multiple ALK inhibitors (ALKi) entered in the therapeutic algorithm of ALK+ patients, multiplying their treatment opportunities. ⋯ In such wide variety of options, we reviewed the preclinical and clinical efficacy data of brigatinib, its pharmacological and safety profile, like also actual and potential future applications in the ALK+ NSCLC scenario. Through a spurious exercise of an indirect comparison with other available 2G ALKi, we tent to summarize the required knowledge to properly choose the best drug at the right time. Furthermore, we reviewed available data on molecular resistance mechanisms and putative therapeutic applications in other contexts, such as ROS1+ NSCLC patients or EGFR+ ones progressing to osimertinib.