FDA Approves Lorlatinib in ALK-Positive Metastatic NSCLC
Posted: Tuesday, November 6, 2018
On November 2, 2018, the U.S. Food and Drug Administration (FDA) granted accelerated approval to lorlatinib (Lorbrena) in the treatment of patients with anaplastic lymphoma kinase (ALK)-positive metastatic non–small cell lung cancer (NSCLC) whose disease has progressed on crizotinib and at least one other ALK inhibitor for metastatic disease or whose disease has progressed on alectinib or ceritinib as the first ALK inhibitor therapy for metastatic disease.
Approval was based on a subgroup of 215 patients with ALK-positive metastatic NSCLC, previously treated with at least 1 ALK kinase inhibitor, enrolled in a nonrandomized, dose-ranging and activity-estimating, multicohort, multicenter study (ClinicalTrials.gov identifier NCT01970865). The major efficacy measures were overall response rate and intracranial overall response rate, according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, as assessed by an independent central review committee.
The overall response rate was 48%, with 4% complete and 44% partial responses. The estimated median response duration was 12.5 months. The intracranial overall response rate in 89 patients with measurable central nervous system lesions according to RECIST version 1.1 was 60%, with 21% complete and 38% partial responses. The estimated median response duration was 19.5 months.
The most common adverse reactions (≥ 20%) in patients receiving lorlatinib were edema, peripheral neuropathy, cognitive effects, dyspnea, fatigue, weight gain, arthralgia, mood effects, and diarrhea. The most common laboratory abnormalities were hypercholesterolemia and hypertriglyceridemia.
The recommended dose of lorlatinib is 100 mg orally once daily.
