Lorlatinib and neurocognitive adverse events: characterization, risk factors, and the potentially mitigative role of social support.

PURPOSE: Lorlatinib is the preferred first-line treatment for patients with ALK+ metastatic non-small cell lung cancer. However, this drug carries high rates of neurocognitive adverse events. This study further characterized these neurocognitive adverse events, examined risk factors, and, for the first time, explored social support as a mitigation strategy.

METHODS

The Mayo Clinic medical record was interrogated for patients prescribed lorlatinib between July 2017 and May 2022, and medical records were reviewed in detail.

RESULTS

Sixty-three patients were prescribed lorlatinib (median age: 59 years (range: 37-82); 31 (49%) men). Twenty-five (40%) developed a neurocognitive adverse event, which had been characterized as follows: "hallucinations," "noise confusion," "obtunded," "memory loss," "trouble doing simple tasks," "mental fogginess," "vivid dreams," and "nightmares." In univariable analyses, age, gender, prior brain metastases, concomitant CYP3A inducers or inhibitors, and married/partner status were not statistically significantly predictive of the neurocognitive adverse event. In multivariable analyses, older age (≥ 65 years) was predictive (HR: 2.6 (95% CI: 1.09, 6.26); p = 0.03). Notably, 3 of 14 married/partnered patients (21%) and 5 of 6 non-married/partnered patients (83%) were hospitalized for a neurocognitive adverse event (p = 0.02, Fisher's Exact test). Medical record content corroborated the importance of married/partnered ("spouse is very supportive") and of non-married/partnered status ("patient lives alone" and "children some distance away").

CONCLUSIONS

This study further characterized lorlatinib-associated neurocognitive adverse events and confirmed older age as a risk factor. Importantly, social support may prevent hospitalization for a neurocognitive adverse event, and, thus, merits further study, perhaps in older patients.