A Comprehensive Report on Alectinib (Alecensa®): A Targeted Therapy for ALK-Positive Non-Small Cell Lung Cancer

Introduction and Overview

Executive Summary

Alectinib is a highly selective, orally bioavailable, second-generation small molecule inhibitor of Anaplastic Lymphoma Kinase (ALK) tyrosine kinase.[1] Marketed under the brand name Alecensa®, it represents a significant advancement in the targeted therapy of anaplastic lymphoma kinase-positive (ALK-positive) non-small cell lung cancer (NSCLC).[3] Developed by Chugai Pharmaceutical, a member of the Roche Group, alectinib has demonstrated superior efficacy and central nervous system (CNS) activity compared to the first-generation inhibitor, crizotinib.[3] Initially established as a standard of care for metastatic disease, alectinib's approval has recently expanded to include adjuvant treatment for early-stage resected NSCLC. This expansion, based on practice-changing clinical trial data, marks a paradigm shift towards curative-intent therapy in this specific molecularly-defined patient population.[6]

The Clinical Challenge of ALK-Positive NSCLC

ALK gene rearrangements, most commonly resulting in the echinoderm microtubule-associated protein-like 4-ALK (EML4-ALK) fusion oncoprotein, are the primary oncogenic drivers in approximately 4% to 5% of NSCLC cases.[1] This distinct molecular subtype of lung cancer often presents in a unique demographic: younger individuals, typically under the age of 55, who are often never-smokers.[7] A defining clinical feature of ALK-positive NSCLC is its high propensity for metastasizing to the central nervous system (CNS). Brain metastases are a major cause of morbidity and mortality in this population, posing a significant therapeutic challenge.[7]