FDA Approves Lorlatinib for Metastatic ALK+ NSCLC
On March 3, 2021, the FDA approved lorlatinib (Lorbrena; Pfizer) for the treatment of patients with metastatic non–small-cell lung cancer (NSCLC) with ALK-positive tumors, as detected by an FDA-approved test.
Approval was also granted by the FDA to the companion diagnostic test, Ventana ALK (D5F3) CDx Assay (Ventana Medical Systems).
The approval of lorlatinib was based on the Study B7461006 clinical trial, which enrolled 296 patients with ALK-positive NSCLC who have not received prior systemic therapy for metastatic disease. Study participants were randomized in a 1:1 ratio to receive lorlatinib 100 mg once daily (n = 149) or crizotinib 250 mg twice daily (n = 147).
Findings showed an overall improvement in progression-free survival (PFS) with a hazard ratio of 0.28 (95% CI, 0.19-0.41; P <.001). The median PFS was not estimable in the lorlatinib arm and 9.3 months (95% CI, 7.6-11.1) in the crizotinib arm.
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 ORR 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, respectively.
The most common (≥20%) adverse reactions associated with lorlatinib included edema, peripheral neuropathy, weight gain, cognitive effects, fatigue, dyspnea, arthralgia, diarrhea, mood effects, hypercholesterolemia, hypertriglyceridemia, and cough.—Emily Bader
Source: US Food and Drug Administration. FDA approves lorlatinib for metastatic ALK-positive NSCLC. March 3, 2021. www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-lorlatinib-metastatic-alk-positive-nsclc. Access March 4, 2021.
