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Neurocognitive Adverse Events Related to Lorlatinib in Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis
by
, , , and
Jonathan N. Priantti
1,
Maysa Vilbert
2,
Francisco Cezar Aquino de Moraes
3
,
Thiago Madeira
4,
Evair Moisés de Lima Santiago
5,
Natasha B. Leighl
6,
Ludimila Cavalcante
7,* and
Nagla F. Abdel Karim
8 1
School of Medicine, Federal University of Amazonas—UFAM, Manaus 69020-160, AM, Brazil
2
Massachusetts General Hospital Cancer Center, Division of Hematology/Oncology, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA
3
School of Medicine, Federal University of Pará—UFPA, Belém 66050-060, PA, Brazil
4
School of Medicine, Federal University of Minas Gerais—UFMG, Belo Horizonte 30130-100, MG, Brazil
5
School of Medicine, Federal University of Mato Grosso do Sul—UFMS, Campo Grande 79070-900, MS, Brazil
6
Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2C4, Canada
7
Department of Medical Oncology and Hematology, University of Virginia Comprehensive Cancer Center, Charlottesville, VA 22903, USA
8
Inova Schar Cancer Institute, University of Virginia, Fairfax, VA 22031, USA
*
Author to whom correspondence should be addressed.
Cancers 2024, 16(14), 2611; https://doi.org/10.3390/cancers16142611 (registering DOI)
Submission received: 21 May 2024
/
Revised: 14 July 2024
/
Accepted: 17 July 2024
/
Published: 22 July 2024
(This article belongs to the Special Issue Cancer-Therapy-Related Adverse Events in Organs)
Simple Summary
This systematic review and meta-analysis aimed to evaluate the neurocognitive adverse events (NAEs) related to lorlatinib in patients with ALK/ROS1-positive non-small cell lung cancer (NSCLC). A random-effects model was used for the meta-analysis and the proportions were pooled with 95% confidence intervals (CIs). In our pooled analysis, cognitive and mood effects were the most important NAEs, with 14% and 11% overall rates, respectively. Speech changes and psychotic effects had an overall frequency of 7% and 5%, respectively. In a subanalysis, mood effects were significantly more frequent in clinical trials than in real-world studies. Therefore, this study showed that lorlatinib-related NAEs are emerging important toxicities in clinical practice. Hence, increasing awareness about NAEs is paramount to improving their recognition and reporting, and thus enhancing patients’ quality of life.
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.
Keywords:
adverse effects; lorlatinib; lung cancer; ALK; ROS1
