Safety of Lorlatinib in ALK-Positive Non-Small-Cell Lung Cancer and Management of Central Nervous System Adverse Events

Kilickap, Saadettin; Ak, Sertac; Dursun, Oldac U; Sendur, Mehmet AN; Karadurmus, Nuri; Demirci, Umut

doi:10.2217/fon-2023-0014

Cited by 4 publications

(1 citation statement)

References 45 publications

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“…It is currently the one ALK TKI that can overcome the G1202R acquired resistance mutation [ 61 ] . However, lorlatinib may lead to CNS side effects that pose challenges for patients in terms of tolerance, including cognitive alterations such as mental impairment, mood effects, and visual and audio hallucinations, which are not observed with a second-generation ALK TKI [ 147 ] . Managing older patients and younger patients in occupations susceptible to this cognitive toxicity requires careful consideration.…”

Section: Discussionmentioning

confidence: 99%

ALK inhibitors in cancer: mechanisms of resistance and therapeutic management strategies

Poei,

Ali,

et al. 2024

Cancer Drug Resist

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Anaplastic lymphoma kinase (ALK ) gene rearrangements have been identified as potent oncogenic drivers in several malignancies, including non-small cell lung cancer (NSCLC). The discovery of ALK inhibition using a tyrosine kinase inhibitor (TKI) has dramatically improved the outcomes of patients with ALK-mutated NSCLC. However, the emergence of intrinsic and acquired resistance inevitably occurs with ALK TKI use. This review describes the molecular mechanisms of ALK TKI resistance and discusses management strategies to overcome therapeutic resistance.

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Section: Discussionmentioning

confidence: 99%

ALK inhibitors in cancer: mechanisms of resistance and therapeutic management strategies

Poei,

Ali,

et al. 2024

Cancer Drug Resist

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Expert Consensus on the Management of Adverse Events of Lorlatinib in the Treatment of ALK+ Advanced Non-small Cell Lung Cancer

Arriola,

de Castro,

García-Campelo

et al. 2024

Clin Drug Investig

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The use of anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs), such as lorlatinib, for the treatment of patients with ALK gene rearrangement (or ALK-positive) non-small cell lung cancer (NSCLC) has been shown to improve the overall survival and quality of life of these patients. However, lorlatinib is not exempt from potential adverse events. Adequate monitoring and management of these adverse events are critical for increasing patient adherence to lorlatinib, thereby maximizing the benefits of treatment and minimizing the risks associated with treatment discontinuation. Considering that the adverse events of lorlatinib can affect different organs and systems, the participation of a multidisciplinary team, including cardiologists, neurologists, internal medicine specialists, and oncology pharmacists, is needed. This article presents specific and pragmatic strategies for identifying and treating the most relevant adverse events associated with lorlatinib in patients with advanced ALK -positive NSCLC based on the clinical experience of a multidisciplinary panel of experts.

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A Case of Severe Psychosis Associated with Lorlatinib

Kunimasa,

Wada,

Matsushima

et al. 2023

JJLC

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━━ Background. Lorlatinib has shown excellent antitumor activity and central nervous system metastases control. We herein report a lung adenocarcinoma patient harboring ALK fusion who developed severe psychotic symptoms due to lorlatinib. Case. A 32-year-old never-smoking man was diagnosed with advanced lung adenocarcinoma harboring ALK fusion. He had no history of psychosis. He had been treated with alectinib for five years and six months. When lorlatinib was introduced as second-line treatment after tumor progression was observed due to cancerous meningitis, he developed a mild confusional state on day 8 of treatment, and on day 9, he threw himself from his third-floor apartment in an acute confusional state with visual and auditory hallucinations. Luckily, no high-energy trauma was observed. The patient showed improvement after withdrawal of lorlatinib and inward treatment at a psychiatric hospital, including anti-psychotic drug administration. Since the patient had no history of psychosis and had shown no similar symptoms during five years of hospitalization, we diagnosed him with a Grade 4 psychiatric disorder induced by lorlatinib. Conclusion. Although extremely rare, lorlatinib can cause serious psychiatric symptoms. Adequate explanation of this possibility is required at the time of induction, and if severe psychiatric symptoms are observed, collaboration with a psychiatrist is necessary.

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Safety of Lorlatinib in ALK-Positive Non-Small-Cell Lung Cancer and Management of Central Nervous System Adverse Events

Cited by 4 publications

References 45 publications

ALK inhibitors in cancer: mechanisms of resistance and therapeutic management strategies

ALK inhibitors in cancer: mechanisms of resistance and therapeutic management strategies

Expert Consensus on the Management of Adverse Events of Lorlatinib in the Treatment of ALK+ Advanced Non-small Cell Lung Cancer

A Case of Severe Psychosis Associated with Lorlatinib

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