Lorlatinib Receives Priority Review in Untreated ALK-Positive Lung Cancer
Posted: Tuesday, January 5, 2021
On December 28, the U.S. Food and Drug Administration (FDA) granted Priority Review to lorlatinib in the first-line treatment of patients with anaplastic lymphoma kinase (ALK)-positive metastatic non–small cell lung cancer (NSCLC). Lorlatinib is a third-generation ALK inhibitor designed to inhibit the most common tumor mutations that drive resistance to current medications and to address brain metastases.
The FDA previously granted accelerated approval to lorlatinib in 2018 to treat patients with ALK-positive metastatic NSCLC whose disease progressed on crizotinib and at least one other ALK inhibitor for metastatic disease or whose disease had progressed on alectinib or ceritinib as the first ALK inhibitor for metastatic disease.
The Priority Review was based on the open-label, parallel, phase III CROWN trial. The clinical trial enrolled 296 patients with previously untreated advanced ALK-positive NSCLC to receive lorlatinib monotherapy (n = 149) or crizotinib monotherapy (n = 147). Results met the primary endpoint of progression-free survival in the lorlatinib group compared with the crizotinib group.
In 32% of patients in the CROWN trial, the most frequently reported serious adverse reactions were pneumonia, dyspnea, pyrexia, mental status changes, and respiratory failure. Fatal adverse reactions observed in 2.7% of patients included pneumonia, myocardial infarction, acute pulmonary edema, embolism, peripheral artery occlusion, and respiratory distress. The most common grade 3 or 4 adverse reactions were edema, peripheral neuropathy, cognitive effects, dyspnea, fatigue, weight gain, arthralgia, mood effects, and diarrhea.