Welcome back to the D.I.S.C.O., FDA’s Drug Information Soundcast in Clinical Oncology, Burst Edition, brought to you by FDA’s Division of Drug Information in partnership with FDA’s Oncology Center of Excellence. Today we’ll be providing another quick update on a recent FDA cancer drug approval.
On March 3, 2021, the FDA granted regular approval to lorlatinib (brand name Lorbrena) for patients with metastatic non-small cell lung cancer whose tumors are anaplastic lymphoma kinase-positive, detected by an FDA-approved test.
The FDA also approved the VENTANA anaplastic lymphoma kinase (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 non-small cell lung cancer.
This current approval is based on data from Study B7461006, a randomized, multicenter, open-label, active-controlled trial conducted in 296 patients with anaplastic lymphoma kinase-positive metastatic non-small cell lung cancer who had not received prior systemic therapy for metastatic disease. Patients were required to have anaplastic lymphoma kinase -positive tumors detected by the VENTANA anaplastic lymphoma kinase (D5F3) CDx assay. Patients were randomized 1:1 to receive lorlatinib or crizotinib.
Study B7461006 demonstrated an improvement in progression-free survival as assessed by blinded independent central review, with a hazard ratio of 0.28. Median progression-free survival was not estimable in the lorlatinib arm and was 9.3 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 objective response rate, as assessed by the blinded independent central review, was 82% in the lorlatinib arm and 23% in the crizotinib arm. The duration of intracranial response was greater than 12 months in 79% and 0% of patients in the lorlatinib and crizotinib arms, respectively.
The most common adverse reactions occurring in more than 20% of patients receiving lorlatinib, including Grade 3-4 laboratory abnormalities, were edema, peripheral neuropathy, weight gain, cognitive effects, fatigue, dyspnea, arthralgia, diarrhea, mood effects, hypercholesterolemia, hypertriglyceridemia, and cough.
This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. This review also used the Real-Time Oncology Review pilot program, which streamlined data submission prior to the filing of the entire clinical application, and the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. The FDA approved this application 8 weeks ahead of the FDA goal date.
Full prescribing information for these approvals can be found on the web at www.fda.gov/drugsatFDA.
Health care professionals should report serious adverse events to FDA’s MedWatch Reporting System at www.fda.gov/medwatch.
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