FDA Expands Approval of Lorlatinib for ALK-Positive Non–Small Cell Lung Cancer
Posted: Friday, March 5, 2021
On March 3, the U.S. Food and Drug Administration moved from accelerated approval to full approval by accepting lorlatinib’s supplemental new drug application. The expanded indication includes first-line treatment of adults with ALK-positive non–small cell lung cancer (NSCLC) whose tumors are detected as ALK-positive via an FDA-approved test. Lorlatinib is a third-generation ALK inhibitor. The FDA also approved the D5F3 CDx Assay as a companion diagnostic for lorlatinib to identify eligible patients with ALK-positive NSCLC.
The FDA’s decision to expand approval is grounded on the results of the open-label, phase III CROWN clinical trial. The trial recruited 296 patients with previously untreated advanced ALK-positive NSCLC who had an Eastern Cooperative Oncology Group performance status of 0 to 2 and were identified as ALK-positive via the D5F3 CDx assay. A total of 149 patients received lorlatinib monotherapy, and 147 patients received crizotinib monotherapy.
Patients administered lorlatinib demonstrated a 72% reduction in the risk of disease progression or death compared with patients given crizotinib monotherapy in a previously untreated patient population (P = .0001). A total of 17 patients in the lorlatinib arm and 13 patients in the crizotinib arm had measurable brain metastases. Further exploratory analysis showed these patients with brain metastases had an 82% intracranial objective response rate with lorlatinib versus 23% with crizotinib. Additionally, the intracranial duration of response was 12 months or longer in 79% of patients in the lorlatinib arm. However, the intracranial duration of response was 0% in the crizotinib arm.
The most common adverse events of any grade and grade 3 or 4 worsening laboratory abnormalities occurred in 20% or more of patients administered lorlatinib included edema (56%), weight gain (38%), peripheral neuropathy (35%), cognitive effects (21%), diarrhea (21%), dyspnea (20%), and hypertriglyceridemia (22%). About 6.7% of patients permanently discontinued lorlatinib because of adverse events.
