Adverse Event Management in Anaplastic Lymphoma Kinase-positive Non-small Cell Lung Cancer

Abstract

The development of oncogene-directed targeted therapies represents a new paradigm in the treatment of non-small cell lung cancer (NSCLC), offering improved outcomes compared with chemotherapy. Rearrangements of the anaplastic lymphoma kinase (ALK) gene are major oncogenic drivers in a subset of NSCLC patients. Since its launch in 2011, the ALK inhibitor crizotinib has become the standard of care inALK-positive NSCLC, but resistance inevitably develops. Ceritinib and alectinib have received regulatory approval: the former in Europe, US and elsewhere in the world, the latter in Japan. ALK inhibitors target multiple pathways, and may therefore be associated with a wide range of adverse events (AEs), including gastrointestinal AEs, hepatotoxicity and, in the case of crizotinib and ceritinib, cardiac effects. While the majority of these AEs are reversible, manageable and not severe, it is important that both physician and patients are aware of toxicities to ensure prompt treatment. This article discusses the management of AEs in patients receiving currently approved ALK inhibitors, including treatment, regular monitoring, drug discontinuation or dose reduction and physician/patient education. Proactive management of AEs enhances patient quality of life and optimises the therapeutic index of these agents.