Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

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

New E-Learning module by Prof Morgillo and Prof Fasano is now available. Watch the presentation and take the CME test today!

E-learning video block

This content is for ESMO members only.



Download slides

Learning objectives

  1. To provide an update on the setting of patients with ALK-positive advanced non-small cell lung cancer (NSCLC) and implications for targeted treatments
  2. To provide a summary of data from clinical studies with crizotinib in patients with advanced NSCLC
  3. To provide an update on the mechanisms of crizotinib acquired resistance
  4. 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.

Last update: 19 May 2022

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.