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.

Clinical Impact of Switching to Ceritinib After Severe AEs Related to Crizotinib/Alectinib in a Novel PTH2R-ALK Fusion Lung Adenocarcinoma: A Case Report

“…The most common AEs of these ALK-TKIs include gastrointestinal effects, fatigue, rash, and hepatotoxicity. 10 In a pooled safety analyses of ALK-TKIs, including clinical trials receiving crizotinib, alectinib or ceritinib, the overall frequency of grade ≥3 AEs was about 22.9–49.7%. 11 Thus, the management of AEs in ALK -positive NSCLC receiving ALK-TKIs should be taken into account.…”

“…Gastrointestinal effects (nausea, vomiting, diarrhea, and constipation) are the most common AEs caused by crizotinib and ceritinib, and have also been reported in alectinib treatment. 10 Since crizotinib, alectinib and ceritinib are metabolized mainly in the liver, hepatotoxicity is frequently observed when treated with these ALK-TKIs. [14][15][16] Therefore, it is recommended that patients taking the three agents should be monitored once a month for liver function tests including ALT, AST, γ-glutamyl transpeptidase (γ-GT) and total bilirubin (TBIL).…”