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4CPS-116 Alectinib hepatic-tolerance in patients with hepatotoxicity background with other anaplastic lymphoma kinase (alk)-inhibitors
  1. AI Idoate Grijalba1,
  2. E Castañon Alvarez2,
  3. B Sangro Gomez-Acebo3,
  4. I Gil Bazo2,
  5. MA Garcia del Barrio1
  1. 1Clinica Universidad de Navarra, Pharmacy, Pamplona, Spain
  2. 2Clinica Universidad de Navarra, Oncology, Pamplona, Spain
  3. 3Clinica Universidad de Navarra, Hepatology, Pamplona, Spain


Background ALK-inhibitors are indicated in adult patients with ALK-positive advanced NSCLC, with crizotinib being the first choice. Hepatotoxicity has been described for crizotinib and ceritinib.

Purpose To describe a case of alectinib hepatic-tolerance in patients with an hepatotoxicity background with other ALK-inhibitors.

Material and methods Data were obtained by review of the electronic medical records. Karch-Lasagna, Naranjo and WHO-UMC algorithms have been used.

Results A 76-year-old male diagnosed with ALK-positive advanced NSCLC (2016) began crizotinib 250 mg twice daily on 27 October 2016 with basal laboratory hepatic parameters in the normal range. An initial brain and thoracic response was observed but 36 days from the start of crizotinib (3 December 2016) a marked elevation appeared in transaminases ALT 1542UI/L (37.6xULN) and AST 684UI/L (18.5xULN) and a minimal rise in total bilirrubin 2.0 mg/dL (1.67xULN). Crizotinib was discontinued and AST recovered its normal range within 24 days and ALT within 32 days. Then ceritinib 750 mg daily was started (3 January 2017) with frequent evaluations of liver function, showing a progressive increase in transaminases from day +8 until 8 March 2017 with maximum values of ALT 214UI/L (5.2xULN) and AST 128UI/L (3.5xULN). Ceritinib was stopped despite the patient presenting brain and thoracic response. Treatment was changed to pembrolizumab 200 mg every 3 weeks and 4 months’ later was discontinued for brain progression. On 12 July 2017 the patient began alectinib 600 mg twice daily with exhaustive hepatic monitoring. Three months’ later he presented an adequate treatment tolerance, without signs of clinical progression and transaminasesin in the normal range.

Karch-Lasagna and Naranjo algorithms established a ‘probable’ relationship between hepatotoxicity and crizotinib/ceritinib. The WHO-UMCalgorithm established this relationship as ‘probable’ to crizotinib and ‘certain’ to ceritinib. In all cases there was a temporal correlation of the facts and an apparent absence of another factor responsible for liver damage.

Conclusion Alectinib may be a therapeutic option in patients with ALK-positive NSCLC who have developed hepatic toxicity to other ALK-inhibitors. Further follow-up is needed to ratify this statement. Hepatic toxicity to ALK-inhibitors has frequently a reversible pattern and transaminases appear to be the most sensitive marker.

References and/or Acknowledgements (ULN)=upper limit normal

No conflict of interest

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