However, the observed outcomes should be interpreted within the context of patient selection. The enrichment for prior responders limits the generalizability to unselected post-TKI populations, including those with primary resistance.

NTRK gene fusions are a critical marker for pediatric soft tissue tumors and are used for precision medicine in these tumors. NTRK gene fusions are used as diagnostic markers for infantile fibrosarcoma, congenital mesoblastic nephroma, and secretory carcinomas, and they play a critical role in the management of these tumors.

Many repotrectinib AEs, including neurological AEs secondary to TRK inhibition, were mitigated with appropriate management, including dose modification and/or pharmacologic intervention.

Psychiatric manifestations were most pronounced: olfactory hallucinations (0.14%, ROR: 91.44, PRR: 91.31), auditory hallucinations (1.3%, ROR: 22.0, PRR: 21.7), and acute psychosis (0.2%, ROR: 22.12, PRR: 22.07).ConclusionsLorlatinib exhibits a multidimensional neuropsychiatric profile with rare but highly specific events. Proactive monitoring of cognitive, mood, speech, and psychotic domains is recommended in clinical practice.

P3, N=194, Recruiting, Nuvation Bio Inc. | N=138 --> 194

Finally, nutritional management is discussed, as is the role of adapted physical activity. In conclusion, this article highlights the importance of proactive monitoring and management of adverse cardiovascular events in patients treated with lorlatinib.

P4, N=41, Active, not recruiting, Guangdong Association of Clinical Trials | Not yet recruiting --> Active, not recruiting | Trial primary completion date: Jul 2025 --> Apr 2026

In this phase IV open-label study, patients with ALK-positive metastatic NSCLC that progressed on first-line alectinib or ceritinib received lorlatinib 100 mg once daily. Lorlatinib continued to show clinically meaningful benefit in patients with previously treated ALK-positive metastatic NSCLC. clinicaltrials.gov identifier is NCT04362072.

Following a second surgical resection and adjuvant radiation therapy, the patient was started on adjuvant targeted therapy with lorlatinib, an ALK kinase inhibitor. This report illustrates the role of immunotherapy and targeted therapy in melanoma treatment.

Combination therapy with osimertinib and entrectinib induced regression of pulmonary lesions, but the patient ultimately discontinued all targeted agents due to the development of severe hepatorenal failure and Escherichia coli-associated sepsis. This case highlights the need for additional research into the safety profile of EGFR-TKI/NTRK inhibitor combination regimens in resistant NSCLC.

Mild adverse events occurred during the combined immunotherapy, including transient hypotension managed with intravenous fluids and abdominal and leg pain that improved with analgesics. In conclusion, our case showed that combination therapy with naxitamab and lorlatinib may improve long-term outcomes and reduce chemotherapy-related toxicity.

Notably, Entrectinib ameliorated LPS-induced memory impairments in vivo. Collectively, these findings indicate that Entrectinib attenuates neuroinflammation and improves memory performance, supporting its potential therapeutic relevance for neuroinflammation-associated cognitive disorders.