FDA expands approval of Lorbrena for ALK-positive metastatic lung cancer
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The FDA expanded the approval of lorlatinib to include the first-line treatment of adults with anaplastic lymphoma kinase-positive metastatic non-small cell lung cancer.
The FDA also approved the Ventana ALK (D5F3) CDx Assay (Ventana Medical Systems Inc.; Roche Diagnostics) as a companion diagnostic to detect anaplastic lymphoma kinase (ALK) for treatment with lorlatinib.
The expanded approval of lorlatinib (Lorbrena, Pfizer), a third-generation ALK inhibitor, is based on results of the randomized phase 3 CROWN trial, which included 296 patients with previously untreated advanced ALK-positive NSCLC randomly assigned to receive 100 mg daily lorlatinib (n = 149) or 250 mg daily crizotinib (Xalkori, Pfizer; n = 147).
As Healio previously reported, results of the study, published in The New England Journal of Medicine, showed lorlatinib conferred a 72% reduction in the risk for progression or death compared with crizotinib (median PFS, not estimable vs. 9.3 months; HR = 0.28; 95% CI, 0.19-0.41).
Among patients with measurable brain metastases at baseline (lorlatinib, n = 17; crizotinib, n = 13), more patients assigned lorlatinib achieved intracranial objective response (82% vs. 23%), the duration of which lasted for 12 months or longer for 79% of patients assigned lorlatinib compared with no patients assigned crizotinib.
The most common adverse events associated with lorlatinib included edema (56%), weight gain (38%), peripheral neuropathy (35%), cognitive effects (21%), diarrhea (21%), dyspnea (20%) and hypertriglyceridemia (22%). Thirty-four percent of patients assigned lorlatinib experienced serious adverse events, the most common of which included pneumonia (4.7%), dyspnea (2.7%), respiratory failure (2.7%), cognitive effects (2%) and pyrexia (2%).
Fatal adverse events — which occurred among 3.4% of patients assigned lorlatinib — included pneumonia, respiratory failure, cardiac failure acute, pulmonary embolism and sudden death (0.7% each).
“The CROWN data have shown Lorbrena can significantly improve outcomes in the first-line treatment of ALK-positive non-small cell lung cancer, including those that present with brain metastases,” Benjamin Solomon, MD, of the department of medical oncology at Peter MacCallum Cancer Centre, said in a manufacturer-issued press release. “This approval is meaningful for my patients because we now have a highly effective treatment option that can delay the progression of a typically aggressive disease.”
This approval converts the 2018 accelerated approval of lorlatinib for second- or third-line treatment of ALK-positive metastatic NSCLC to full approval.
FDA reviewed this application under Project Orbis, which provides a framework for concurrent submission and review of oncology drugs among international partners, and using the Real-Time Oncology Review pilot program, which streamlines data submission. The application previously received priority review and orphan drug designation.
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