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Monitoring and Managing Lorlatinib Adverse Events in the Portuguese Clinical Setting: A Position Paper

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Abstract

Rearrangements in the anaplastic lymphoma kinase (ALK) and proto-oncogene tyrosine-protein kinase ROS (ROS1) genes characterise two distinct molecular subsets of non-small cell lung cancer (NSCLC) tumours. Lorlatinib is a third-generation ALK/ROS1 tyrosine kinase inhibitor (TKI) shown to have systemic and intracranial activity in treatment-naive patients and in those who progressed on first- and second-generation TKIs. Despite being generally well tolerated, lorlatinib has a unique and challenging safety profile that includes hyperlipidaemia and central and peripheral nervous system adverse events (AEs). This article summarises a set of strategies designed to monitor and manage lorlatinib-related AEs that were agreed upon by a multidisciplinary panel of specialists in a meeting held in July 2020. Among the recommendations hereby described, special emphasis was placed on communication: prescribing physicians should inform patients and their families/caregivers about the likelihood and nature of lorlatinib AEs, encouraging them to report any symptoms, while at the same time reassuring them that most events are manageable and resolve spontaneously and have little to no interference with cancer treatment. Importantly, all patients should undergo a set of baseline assessments, including biochemical analysis, evaluation of cardiovascular risk, electrocardiogram (ECG), neurological evaluation and contrast-enhanced magnetic resonance imaging of the brain, which should be repeated regularly during lorlatinib treatment. Supportive medications to treat or relieve lorlatinib AEs were also discussed, as were the conditions requiring specialist consultations and/or adjustments in lorlatinib therapy. The overall goal of this article is to serve as a practical guide for oncologists to systematically and effectively approach lorlatinib AEs.

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Acknowledgements

The authors would like to express their gratitude to Dr. Ricardo da Luz for critically reviewing the manuscript. Medical writing support was provided by Catarina L. Santos at Springer Healthcare Iberica, and editorial assistance was provided post-submission by Georgii Filatov of Springer Healthcare Communications. Medical writing and editorial assistance was funded by Pfizer.

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Authors and Affiliations

  1. Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal

    Fernando Barata

  2. Hospital de Santa Cruz, Lisboa, Portugal

    Carlos Aguiar

  3. Psychiatric Imaging Group, MRC London Institute of Medical Sciences (LMS), Imperial College London, London, UK

    Tiago Reis Marques

  4. Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK

    Tiago Reis Marques

  5. Fundação Champalimaud, Lisboa, Portugal

    José Bravo Marques

  6. Centro Hospitalar Universitário de São João, Porto, Portugal

    Venceslau Hespanhol

  7. Faculdade Medicina do Porto, Porto, Portugal

    Venceslau Hespanhol

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  1. Fernando Barata
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  5. Venceslau Hespanhol
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Correspondence to Fernando Barata.

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Funding

This study was funded by Pfizer.

Conflicts of Interest

FB received speaker’s fees and honoraria from AstraZeneca, Boeringher Ingelheim, Bristol Myers Squibb, MSD Oncology, Pfizer, Roche and Takeda for participating in advisory boards. CA has received honoraria from Pfizer for consulting. TRM has conducted research funded by the Medical Research Council (UK), King´s Health Partners and King’s College London, and has received honoraria for speaking and chairing engagements from Lundbeck, Janssen, Astellas and Pfizer. JBM and VH received honoraria from Pfizer for participating in advisory boards.

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All authors approved the publication of this article.

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Data sharing is not applicable as no new data were created or analysed in this study.

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Author Contributions

FB devised and coordinated the project. All authors participated in the advisory board in which the recommendations were discussed, and contributed to the writing of the manuscript. All authors also read and approved the final version of this manuscript.

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Barata, F., Aguiar, C., Marques, T.R. et al. Monitoring and Managing Lorlatinib Adverse Events in the Portuguese Clinical Setting: A Position Paper. Drug Saf 44, 825–834 (2021). https://doi.org/10.1007/s40264-021-01083-x

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