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FDA Approves Lorlatinib for Metastatic ALK-Positive NSCLC


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On March 3, the U.S. Food and Drug Administration (FDA) granted regular approval to lorlatinib (Lorbrena) for patients with metastatic non–small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK)-positive, as detected by an FDA-approved test.

The FDA also approved the Ventana ALK (D5F3) CDx Assay as a companion diagnostic for lorlatinib.

Lorlatinib received accelerated approval in November 2018 for the second- or third-line treatment of ALK-positive metastatic NSCLC.

Study B7461006

This current approval is based on data from Study B7461006, a randomized, multicenter, open-label, active-controlled trial conducted in 296 patients with ALK-positive metastatic NSCLC who had not received prior systemic therapy for metastatic disease. Patients were required to have ALK-positive tumors detected by the VENTANA ALK (D5F3) CDx assay. Patients were randomly assigned 1:1 to receive lorlatinib at 100 mg orally once daily (n = 149) or crizotinib at 250 mg orally twice daily (n = 147).

Study B7461006 demonstrated an improvement in progression-free survival as assessed by blinded independent central review, with a hazard ratio of 0.28 (95% confidence interval = 0.19–0.41, P < .0001). Median progression-free survival was not estimable in the lorlatinib arm and was 9.3 months (95% CI = 7.6 months–11.1 months) for those treated with crizotinib. Overall survival data were immature at the progression-free survival analysis.

Central nervous system involvement was assessed in all patients. There were 17 patients in the lorlatinib arm and 13 in the crizotinib arm with measurable central nervous system lesions based on baseline brain imaging. Among these patients, the intracranial overall response rate, as assessed by the blinded independent central review, was 82% (95% CI = 57%–96%) in the lorlatinib arm and 23% (95% CI = 5%–54%) in the crizotinib arm. The duration of intracranial response was ≥ 12 months in 79% and 0% of patients in the lorlatinib and crizotinib arms, respectively.

The most common adverse reactions (incidence ≥ 20%), including grade 3 to 4 laboratory abnormalities, in patients receiving lorlatinib were edema, peripheral neuropathy, weight gain, cognitive effects, fatigue, dyspnea, arthralgia, diarrhea, mood effects, hypercholesterolemia, hypertriglyceridemia, and cough.

The recommended lorlatinib dose is 100 mg orally once daily.


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