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Neurocognitive Adverse Events Related to Lorlatinib in Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis

Affiliations
  • 1School of Medicine, Federal University of Amazonas-UFAM, Manaus 69020-160, AM, Brazil.
  • 2Massachusetts General Hospital Cancer Center, Division of Hematology/Oncology, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
  • 3School of Medicine, Federal University of Pará-UFPA, Belém 66050-060, PA, Brazil.
  • 4School of Medicine, Federal University of Minas Gerais-UFMG, Belo Horizonte 30130-100, MG, Brazil.
  • 5School of Medicine, Federal University of Mato Grosso do Sul-UFMS, Campo Grande 79070-900, MS, Brazil.
  • 6Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2C4, Canada.
  • 7Department of Medical Oncology and Hematology, University of Virginia Comprehensive Cancer Center, Charlottesville, VA 22903, USA.
  • 8Inova Schar Cancer Institute, University of Virginia, Fairfax, VA 22031, USA.

Published on:

July 27, 2024

Abstract

Lorlatinib has been FDA-approved as a systemic therapy for ALK/ROS1-positive non-small cell lung cancer (NSCLC) patients. However, it has been associated with an increased frequency of neurocognitive adverse events (NAEs). Therefore, we conducted a systematic review and meta-analysis to assess the NAEs related to lorlatinib therapy in NSCLC patients. PubMed, Scopus, the Cochrane Library, and prominent conference proceedings were searched for eligible studies of lorlatinib in NSCLC patients. NAEs included cognitive, mood, speech, and psychotic effects. A total of 1147 patients from 12 studies were included; 62% had brain metastases. A pooled analysis of NAEs showed frequencies of cognitive effects of 14.57% (95% CI, 8.37 to 24.14, I2 = 84%), mood effects of 11.17% (95% CI, 5.93 to 20.07, I2 = 84%), speech effects of 7.24% (95% CI, 3.39 to 15.20, I2 = 72%), and psychotic effects of 4.97% (95% CI, 3.27 to 7.49, I2 = 21%). Clinical trials reported a significantly higher frequency of mood effects than was indicated by real-world data. These results highlight the importance of educating patients and healthcare professionals about lorlatinib-related NAEs for early detection and management to improve NSCLC patients’ quality of life.

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