Elsevier

Lung Cancer

Volume 120, June 2018, Pages 60-61
Lung Cancer

Lorlatinib – Induced pulmonary arterial hypertension

https://doi.org/10.1016/j.lungcan.2018.03.023Get rights and content

Highlights

  • We report here the first cases, to our knowledge, of pulmonary arterial hypertension induced by lorlatinib.

  • It's first time that a tyrosine kinase inhibitor for lung cancer is associated with pulmonary hypertension.

  • Physicians managing patients under lorlatinib should urgently be made aware of this severe complication.

Abstract

We report here the first cases, to our knowledge, of pulmonary arterial hypertension induced by lorlatinib.

It s the first time that a tyrosine kinase inhibitor for lung cancer is associated with pulmonary arteriel hypertension.

Section snippets

Case 1

A 55-year-old woman had previously been treated with various chemotherapies for a metastatic NSCLC from 2010 to December 2014. Then she received crizonitib and ceretinib because of tumor progression, as her NSLC expressed ALK rearrangement. A progression on ceretinib led to starting lorlanitib 50 mg bid in August, 2017.

One month later, she complained of rapidly progressive NYHA functional class IV dyspnea. She was unable to perform a walk test. Echocardiography estimated systolic pulmonary

Case 2

A 64-year-old male patient exhibited metastatic NSCLC with ALK rearrangement had been successively treated with crizonitib, ceretinib then lorlanitib 50 mg bid, because of uncontrolled disease.

Two months after lorlatinib introduction, he complained of a dramatically increasing afebrile dyspnea (in NYHA functional class III). He walked 368 m with oxygenotherapy at 5 L/min in a 6 min walk test. Systolic pulmonary arterial pressure on echocardiography was estimated at 62 mmHg with apparent normal

Acknowledgement

We acknowledge the French pulmonary hypertension pharmacovigilance network, VIGIAPATH, supported by the Agence Nationale de Sécurité du Médicament et des Produits de Santé (ANSM).

References (6)

  • A.S. Tsao et al.

    Scientific advances in lung cancer

    J. Thorac. Oncol.

    (2015)
  • E. Felip et al.

    MA07. 11 safety and efficacy of lorlatinib (PF-06463922) in patients with advanced ALK+ or ROS1+ Non-Small-Cell Lung Cancer (NSCLC)

    J. Thorac. Oncol.

    (2017)
  • N.P. Shah et al.

    Clinical features of pulmonary arterial hypertension in patients receiving dasatinib

    Am. J. Hematol.

    (2015)
There are more references available in the full text version of this article.

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    Treatment with ALK inhibitors is usually well tolerated; however, there are common class adverse events such as nausea, vomiting, diarrhea, pneumonitis, and cardiac toxicity.12 Some less common adverse events have been reported as well including rectal perforation,13 cataract, macular edema or blindness,14,15 osteitis,16 ventricular fibrillation,17,18 pulmonary arterial hypertension,19 pancreatitis,20 cholestasis,21 alopecia,22 proteinuria,23 myasthenia gravis,24 toxic epidermal necrolysis,25 sarcoid-like reaction,26 and photosensitivity.27 Treatment discontinuation due to adverse events among different ALK inhibitors were as follow: 12% with crizotinib as in the PROFILE 1014 trial,28 5% with ceritinib as in the ASCEND 4 trial,29 11% with alectinib as in the ALEX trial,30 12% with brigatinib as in the ALTA-1L trial,10 and 7% with lorlatinib as in the CROWN trial.31

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Thses authors are equal contribution as first authors.

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