Vortioxetine for Cognitive Function in ALK-positive NSCLC Treated With Lorlatinib

Summary

This observational study evaluates whether vortioxetine - an antidepressant medication with cognitive-enhancing properties - can reduce the neurological and cognitive side effects associated with lorlatinib treatment in patients with non-small cell lung cancer (NSCLC) harboring ALK or ROS1 gene rearrangements. Lorlatinib is a highly effective third-generation tyrosine kinase inhibitor, but it causes neuropsychological adverse events (NAEs) in approximately 42% of patients, including cognitive impairment, mood changes, and speech disturbances. Vortioxetine has demonstrated cognitive improvement in depressed patients and in preclinical models of androgen deprivation therapy-induced cognitive impairment. Twenty-four adult patients with ALK/ROS1-positive NSCLC receiving lorlatinib as standard care and prescribed vortioxetine (10-20 mg/day) for NAE management will be enrolled. Comprehensive neuropsychological assessments and quality-of-life questionnaires will be conducted at baseline, week 6, week 12, and month 6 to document changes in cognitive function, depressive symptoms, and quality of life.

Eligibility

Inclusion Criteria:

* Histologically confirmed diagnosis of ALK/ROS1-positive non-small cell lung cancer (NSCLC), stage IIIB/IV.
* Currently receiving lorlatinib as part of the standard therapeutic regimen.
* Documented neurocognitive adverse events (NAEs) attributable to lorlatinib.
* Age \>= 18 years.
* ECOG performance status 0-2.
* Ability to understand and sign informed consent.
* Expected survival \>= 6 months.
* Planned initiation of vortioxetine as part of standard care.
* Ability to complete neuropsychological tests and questionnaires in Spanish.

Exclusion Criteria:

* Prior diagnosis of major cognitive impairment unrelated to cancer treatment.
* Current use of another antidepressant that cannot be discontinued.
* Uncontrolled major psychiatric disorder.
* History of uncontrolled epilepsy or recent seizures.
* Severe hepatic or renal impairment.
* Known hypersensitivity to vortioxetine.
* Participation in another clinical trial within the past 30 days.
* Inability to provide informed consent.
* Life expectancy \< 3 months.
* Contraindications to vortioxetine (e.g., concomitant MAOI use).
* Prior vortioxetine use.
* Severe psychiatric disorders or significant cognitive impairment unrelated to lorlatinib.

Conditions8

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