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Loratinib

Lorlatinib approved for the first-line treatment of adult patients with metastatic anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC).

 

Lorbrena trade name.

 

 

Radomized, open-label, parallel 2-arm phase 3 CROWN trial, designed to evaluate lorlatinib compared with crizotinib in previously untreated patients.

 

 

Treatment with lorlatinib demonstrated a 72% reduction in the risk for progression or death.

 

 

The intracranial objective response rate was 82%  compared with 23% with crizotinib. 

 

 

The intracranial duration of response was 12 months or longer in 79% of patients treated with lorlatinib compared with 0% of those who received crizotinib.

 

 

Adverse events: edema (56%), weight gain (38%), peripheral neuropathy (35%), cognitive effects (21%), diarrhea (21%), dyspnea (20%), and hypertriglyceridemia (22%). 

 

 

Serious AEs occurred in 34% of patients: pneumonia (4.7%), dyspnea (2.7%), respiratory failure (2.7%), cognitive effects (2.0%), and pyrexia (2.0%). 

 

 

Fatal AEs occurred in 3.4% of the lorlatinib arm, and included pneumonia (0.7%), respiratory failure (0.7%), cardiac failure acute (0.7%), pulmonary embolism (0.7%), and sudden death (0.7%). 

 

 

 

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