Lorlatinib is a third-generation inhibitor of anaplastic lymphoma kinase (ALK). Previous research has shown that it could have antitumor activity in previously treated patients with ALK-positive non-small lung cancer (NSCLC). But the efficacy of lorlatinib when compared with that of crizotinib is not clear. This study aims to compare the efficacy of lorlatinib and crizotinib as first-line therapy for ALK-positive lung cancer.

This global, randomized, phase 3 trial included a total of 296 patients with advanced ALK-positive NSCLC. The patients were assigned randomly to receive lorlatinib and crizotinib. The primary outcome of the study was progression-free survival, along with independently assessed objective response and intracranial response.

 At 12 months, 78% of patients in the lorlatinib group and 39% of patients in the crizotinib group were alive without disease progression. An objective response was reported in 76% of the patients in the lorlatinib group and 58% of those in the crizotinib group. Commonly associated adverse events lorlatinib were hyperlipidemia, increased weight, edema, peripheral neuropathy, and cognitive effects. Besides, lorlatinib was also associated with more grade-3 and grade-4 adverse events.

The research concluded that lorlatinib was associated with longer progression-free survival in patients with ALK-positive lung cancer when compared with crizotinib.

Ref: https://www.nejm.org/doi/full/10.1056/NEJMoa2027187