Lung Cancer
Read Time: 2 mins

Adverse Event Management in Anaplastic Lymphoma Kinase-positive Non-small Cell Lung Cancer

Copy Link
Published Online: Nov 26th 2015 European Oncology & Haematology, 2015;11(2):94–9
Quick Links:
Article Information

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 in ALK-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.


Alectinib, ceritinib, crizotinib, ALK-positive non-small cell lung cancer


The development of targeted therapies has resulted in a new paradigm in the treatment of anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC), and ALK tyrosine kinase inhibitors (TKIs) are the standard of care in ALK-positive NSCLC. However, ALK inhibitors also present new challenges. As a result of improved outcomes, patients will be receiving these agents for long periods of time. Furthermore, these drugs often target multiple pathways and may cause a range of toxicities. Since ALK inhibitors will be used by a multidisciplinary team in a specific subgroup of patients, physicians are likely to have limited experience in their use.1 It is therefore essential that physicians and caregivers are aware of treatment-related adverse events (AEs) in order to optimise their management and thus enhance the patient’s quality of life. This article will focus on the management of AEs in ALK-positive NSCLC receiving targeted therapy.

The Role of ALK Signalling in NSCLC and the Use of Tyrosine Kinase Inhibitors

NSCLC is characterised by extensive genomic instability, which results in dramatic functional changes and is the molecular basis of lung carcinogenesis.2,3 Among the most frequently encountered targetable genetic alterations are chromosomal rearrangements of the ALK gene, which encodes a receptor tyrosine kinase. The ALK association with NSCLC was reported in 2007, following the discovery of a small inversion within chromosome 2p that juxtaposes the 5′ end of the echinoderm microtubule-associated protein-like 4 (EML4) gene with the 3′ end of the ALK gene, resulting in the novel fusion oncogene EML4-ALK in NSCLC cells.4 ALK-rearranged tumours depend on ALK for growth and survival and are therefore sensitive to ALK inhibitors.4,5 ALK-positive NSCLC accounts for 4–5 % of adenocarcinomas of the lung,6 and is more common in males than in females.7 The majority of cases of ALK rearrangement arise in patients with no smoking history or light smokers.8,9

ALK inhibitors have shown dramatic and sustained responses in clinical studies. The first-in-class crizotinib (Xalkori®, Pfizer) is an oral, small-molecule TKI that targets ALK, MET and ROS1,10 and received accelerated approval from the US Food and Drug Administration (FDA) in 2011.11 Since its launch, crizotinib has become the standard of care in ALK-positive NSCLC. However, disease typically relapses

Article Information:

Christian Rolfo has served on the Novartis International Speakers Bureau. Solange Peters and Ignacio Gil-Bazo have no conflicts of interest to declare.


Christian Rolfo, Associate Professor, University Hospital Antwerp Oncology, Head of Phase I Early Clinical Trials Unit, Antwerp, Belgium.


The publication of this article was supported by Novartis, who were given the opportunity to review the article for scientific accuracy before submission. Any resulting changes were made at the author’s discretion.


This article is published under the Creative Commons Attribution Noncommercial License, which permits any non-commercial use, distribution, adaptation and reproduction provided the original author(s) and source are given appropriate credit.


Medial writing assistance was provided by Katrina Mountfort at Touch Medical Media and funded by Novartis.



Further Resources

Share this Article
Related Content In Lung Cancer
  • Copied to clipboard!
    accredited arrow-down-editablearrow-downarrow_leftarrow-right-bluearrow-right-dark-bluearrow-right-greenarrow-right-greyarrow-right-orangearrow-right-whitearrow-right-bluearrow-up-orangeavatarcalendarchevron-down consultant-pathologist-nurseconsultant-pathologistcrosscrossdownloademailexclaimationfeedbackfiltergraph-arrowinterviewslinkmdt_iconmenumore_dots nurse-consultantpadlock patient-advocate-pathologistpatient-consultantpatientperson pharmacist-nurseplay_buttonplay-colour-tmcplay-colourAsset 1podcastprinter scenerysearch share single-doctor social_facebooksocial_googleplussocial_instagramsocial_linkedin_altsocial_linkedin_altsocial_pinterestlogo-twitter-glyph-32social_youtubeshape-star (1)tick-bluetick-orangetick-red tick-whiteticktimetranscriptup-arrowwebinar Sponsored Department Location NEW TMM Corporate Services Icons-07NEW TMM Corporate Services Icons-08NEW TMM Corporate Services Icons-09NEW TMM Corporate Services Icons-10NEW TMM Corporate Services Icons-11NEW TMM Corporate Services Icons-12Salary £ TMM-Corp-Site-Icons-01TMM-Corp-Site-Icons-02TMM-Corp-Site-Icons-03TMM-Corp-Site-Icons-04TMM-Corp-Site-Icons-05TMM-Corp-Site-Icons-06TMM-Corp-Site-Icons-07TMM-Corp-Site-Icons-08TMM-Corp-Site-Icons-09TMM-Corp-Site-Icons-10TMM-Corp-Site-Icons-11TMM-Corp-Site-Icons-12TMM-Corp-Site-Icons-13TMM-Corp-Site-Icons-14TMM-Corp-Site-Icons-15TMM-Corp-Site-Icons-16TMM-Corp-Site-Icons-17TMM-Corp-Site-Icons-18TMM-Corp-Site-Icons-19TMM-Corp-Site-Icons-20TMM-Corp-Site-Icons-21TMM-Corp-Site-Icons-22TMM-Corp-Site-Icons-23TMM-Corp-Site-Icons-24TMM-Corp-Site-Icons-25TMM-Corp-Site-Icons-26TMM-Corp-Site-Icons-27TMM-Corp-Site-Icons-28TMM-Corp-Site-Icons-29TMM-Corp-Site-Icons-30TMM-Corp-Site-Icons-31TMM-Corp-Site-Icons-32TMM-Corp-Site-Icons-33TMM-Corp-Site-Icons-34TMM-Corp-Site-Icons-35TMM-Corp-Site-Icons-36TMM-Corp-Site-Icons-37TMM-Corp-Site-Icons-38TMM-Corp-Site-Icons-39TMM-Corp-Site-Icons-40TMM-Corp-Site-Icons-41TMM-Corp-Site-Icons-42TMM-Corp-Site-Icons-43TMM-Corp-Site-Icons-44TMM-Corp-Site-Icons-45TMM-Corp-Site-Icons-46TMM-Corp-Site-Icons-47TMM-Corp-Site-Icons-48TMM-Corp-Site-Icons-49TMM-Corp-Site-Icons-50TMM-Corp-Site-Icons-51TMM-Corp-Site-Icons-52TMM-Corp-Site-Icons-53TMM-Corp-Site-Icons-54TMM-Corp-Site-Icons-55TMM-Corp-Site-Icons-56TMM-Corp-Site-Icons-57TMM-Corp-Site-Icons-58TMM-Corp-Site-Icons-59TMM-Corp-Site-Icons-60TMM-Corp-Site-Icons-61TMM-Corp-Site-Icons-62TMM-Corp-Site-Icons-63TMM-Corp-Site-Icons-64TMM-Corp-Site-Icons-65TMM-Corp-Site-Icons-66TMM-Corp-Site-Icons-67TMM-Corp-Site-Icons-68TMM-Corp-Site-Icons-69TMM-Corp-Site-Icons-70TMM-Corp-Site-Icons-71TMM-Corp-Site-Icons-72