Managing Treatment–Related Adverse Events Associated with Alk Inhibitors

Abstract

Anaplastic lymphoma kinase (ALK) rearrangements have been identified as key oncogenic drivers in a small subset of non-small-cell lung cancers (xnsclcs). Small-molecule Alk kinase inhibitors such as crizotinib have transformed the natural history of nsclc for this subgroup of patients. Because of the prevalence of nsclc, ALK-positive patients represent an important example of the paradigm for personalized medicine. Although Alk inhibitors such as crizotinib are well tolerated, there is a potential for adverse events to occur. Proactive monitoring, treatment, and education concerning those adverse events will help to optimize the therapeutic index of the drugs. The present review summarizes the management of treatment-related adverse events that can arise with Alk inhibitors such as crizotinib.

Non–Small Cell Lung Cancer, Version 5.2017, NCCN Clinical Practice Guidelines in Oncology

“…61,81,[86][87][88] Crizotinib has relatively few side effects (eg, eye disorders, edema, transient changes in renal function). 87,89,90 However, a few patients have had life-threatening pneumonitis; crizotinib should be discontinued in these patients. 83 Patients whose disease responds to crizotinib may have rapid improvement in symptoms (eg, cough, dyspnea, pain); median time to progression on crizotinib is approximately 7 months to 1 year.…”

Kinase inhibitors and monoclonal antibodies in oncology: clinical implications

“…It is important to correct serum electrolyte imbalances, such as hypokalaemia or hypo magnesaemia, which represent additional risk factors that can facilitate and/or trigger cardiac arrhythmias. Bradyarrhythmias do not typically occur with kinase inhibitors or mAbs, except with the ALK inhibitor crizotinib, where grades 1 and 2 bradycardias have been reported in 5% of treated patients 55 . Decrease in heart rate has been hypothesized to be associated with higher response rates to treatment 56,57 , but definitive conclusions cannot be made.…”

Advancing the Management of Non-small Cell Lung Cancer

“…73 Although ALK inhibitors are generally well tolerated, they are associated with a wide range of treatment-emergent adverse events (AEs), including gastrointestinal AEs and hepatotoxicity, but most are manageable and reversible. 74 Several other agents are in clinical development. The dual ALK/EGFR inhibitor brigatinib showed promising activity in ALK-positive NSCLC patients with brain metastasis following crizotinib.…”