ESMO E-Learning: Important Pathways to Target in (Advanced) NSCLC - A Focus on ALK Inhibition in Non-Small-Cell Lung Cancer (NSCLC)

Learning Objectives

  • 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
Title Duration Content CME Points CME Test
Important Pathways to Target in (Advanced) NSCLC: A Focus on ALK Inhibition in Non-Small-Cell Lung Cancer (NSCLC) 35 min. 73 slides 1 Take Test
Floriana Morgillo
Floriana Morgillo
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Morena Fasano
Morena Fasano
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Anaplastic lymphoma kinase (ALK) is positive in 2-5% of patients with non-small cell lung cancer (NSCLC). 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 in patients with ALK-positive NSCLC and provides evidence from clinical studies with ALK inhibitors. The authors elaborate the results from clinical studies with crizotinib, explain the mechanisms of crizotinib acquired resistance and summarise the latest data from clinical studies with the next-generation ALK inhibitors (ceritinib, alectinib, lorlatinib and brigatinib). 

From the aspect of ALK inhibition in the crizotinib-failure setting, the authors compare the systemic efficacy and central nervous system activity of next-generation ALK inhibitors and consider the need for establishing the most appropriate drug sequence in that setting. 

This module has been developed from a previous E-Learning module that elaborated different pathways relevant for targeted treatments in patiens with advanced NSCLC. Crizotinib has been first in class ALK inhibitor to be registered for all lines of treatments in ALK-positive advanced patients. By elaborating the common resistance mechanisms to crizotinib and providing an overview of intensive clinical development of next-generation ALK inhibitors, the authors explain the recent changes to be considered in clinical practice: namely, alectinib should be considered as a new standard in first-line treatment of ALK-positive NSCLC.

Last update: 01 October 2018

The authors have reported no conflicts of interest