Systematic review and meta-analysis of selected toxicities of approved ALK inhibitors in metastatic non-small cell lung cancer

Rubens Barros Costa _, Ricardo L.B. Costa, Sarah M. Talamantes, Jason B. Kaplan, Manali A. Bhave, Alfred Rademaker, Corinne Miller, Benedito A. Carneiro, Devalingam Mahalingam and Young Kwang Chae

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Oncotarget. 2018; 9:22137-22146. https://doi.org/10.18632/oncotarget.25154

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Rubens Barros Costa1, Ricardo L.B. Costa2, Sarah M. Talamantes3, Jason B. Kaplan1, Manali A. Bhave1, Alfred Rademaker4, Corinne Miller5, Benedito A. Carneiro6, Devalingam Mahalingam1 and Young Kwang Chae1

1Developmental Therapeutics Program, Northwestern University, Chicago, IL, USA

2Department of Breast Oncology, Lee Moffitt Cancer Center, Tampa, USA

3Northwestern University, Feinberg School of Medicine, Chicago, IL, USA

4Northwestern University, Department of Preventive Medicine, Chicago, IL, USA

5Galter Health Sciences Library, Northwestern University, Chicago, IL, USA

6Life Span Cancer Institute, Providence, RI, USA

Correspondence to:

Rubens Barros Costa, email: [email protected]

Keywords: crizotinib; ceritinib; alectinib; brigatinib; anaplastic lymphoma kinase

Received: January 20, 2018     Accepted: April 04, 2018     Published: April 24, 2018


Introduction: Anaplastic lymphoma kinase (ALK) inhibitors are the mainstay treatment for patients with non-small cell lung carcinoma (NSCLC) harboring a rearrangement of the ALK gene or the ROS1 oncogenes. With the recent publication of pivotal trials leading to the approval of these compounds in different indications, their toxicity profile warrants an update.

Materials and Methods: A systematic literature search was performed in July 2017. Studies evaluating US FDA approved doses of one of the following ALK inhibitors: Crizotinib, Ceritinib, Alectinib or Brigatinib as monotherapy were included. Data were analyzed using random effects meta-analysis for absolute risks (AR), study heterogeneity, publication bias and differences among treatments.

Results: Fifteen trials with a total of 2,005 patients with evaluable toxicity data were included in this report. There was significant heterogeneity amongst different studies. The pooled AR of death and severe adverse events were 0.5% and 34.5%, respectively. Grade 3/4 nausea, vomiting, diarrhea, and constipation were uncommon: 2.6%, 2.5%, 2.7%, 1.2%, respectively.

Conclusions: ALK inhibitors have an acceptable safety profile with a low risk of treatment-related deaths. Important differences in toxicity profile were detected amongst the different drugs.

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