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- To provide an update on the setting of patients with ALK-positive advanced non-small cell lung cancer (NSCLC) and implications for targeted treatments
- To provide a summary of data from clinical studies with crizotinib in patients with advanced NSCLC
- To provide an update on the mechanisms of crizotinib acquired resistance
- To elaborate evidence on clinical effectiveness of next-generation ALK inhibitors in patients with advanced NSCLC
This E-Learning module is an update of a previous module focusing on anaplastic lymphoma kinase (ALK) inhibition and implications for the treatment of patients with advanced non-small cell lung cancer (NSCLC). The authors elaborate on the diagnosis and ALK testing, prognostic impact of ALK rearrangement, and detail the results of clinical trials with crizotinib, a first in class ALK inhibitor, patterns of progression and mechanisms of resistance to crizotinib. They summarise the results from the clinical trials with next-generation ALK inhibitors, ceritinib, alectinib, brigatinib and lorlatinib Furthermore, they elaborate brain efficacy of ALK inhibitors and other upfront and as next-line treatment options discussing the present situation in terms of optimal sequence determination.
ALK rearrangement frequency is reported in 2-5% of all patients with NSCLC, and 33% in EGFR negative never smokers. At least 28 different EML4-ALK variants have been identified in NSCLC, but clinical significance of each variant is unknown. Patients with ALK-positive disease tend to be younger, never-light smokers, presenting with adenocarcinoma, adenosquamous carcinoma, and rarely squamous cell carcinoma (SCC). Pleural and pericardial effusion and brain metastases are more common among patients with ALK-positive tumours.
ALK testing should be carried out simultaneously with EGFR at diagnosis of advanced NSCLC. ALK mutation testing is recommended in all patients with advanced NSCLC of a non-squamous subtype, regardless of smoking history. Testing is not recommended in patients with an unequivocal diagnosis of SCC, except in never/former light smokers.
This E-Learning module elaborates clinical characteristics of patients with ALK-positive NSCLC and provides evidence from clinical trials with ALK inhibitors. Crizotinib was the first in class ALK inhibitor registered for the treatment of patients with ALK-positive NSCLC. By elaborating the mechanisms of resistance and providing an overview of clinical trials with next-generation ALK inhibitors, the authors underline the intense drug developments in that setting and emphasize on the need for establishing the most appropriate treatment sequence.
Declaration of interest
Floriana Morgillo and Morena Fasano have no interests to declare.