The U.S. Food and Drug Administration approved lorlatinib for patients with ALK-positive metastatic non-small cell lung cancer (NSCLC) whose disease has progressed on crizotinib and at least one other anaplastic lymphoma kinase (ALK) inhibitor for metastatic disease, or whose disease has progressed on alectinib or ceritinib as the first ALK inhibitor therapy for metastatic disease.
The decision to approve the third-generation ALK tyrosine kinase inhibitor (TKI) was based on results from the non-randomized, dose-ranging, activity-estimating, multicohort, multicenter, phase I/II B7461001 study that included 215 patients with ALK-positive metastatic NSCLC who were previously treated with one or more ALK TKIs.
This is my initial reaction to the data and approval as well.The master ALK protocol will be helpful.There are some odd target effects of lorlatinib FDA approval language-if brigatinib gets 1L approval, the lorlatinib label isn’t written in such a way as to allow 2L lorlatinib
— Sandip Patel MD (@PatelOncology) November 3, 2018
The overall response rate (ORR) was 48 percent (95% CI, 42-55), and 57 percent of these patients had previously received more than one ALK TKI.
Among 295 ALK-positive or ROS1-positive patients who received lorlatinib 100 mg once daily in the B7461001 study, the most common adverse events (AEs) were edema, peripheral neuropathy, cognitive effects, dyspnea, fatigue, weight gain, arthralgia, mood effects, and diarrhea. The most common laboratory abnormalities were hypercholesterolemia, hypertriglyceridemia, anemia, hyperglycemia, increased aspartate aminotransferase, hypoalbuminemia, increased alanine aminotransferase, increased lipase, and increased alkaline phosphatase. Serious AEs occurred in 32 percent of patients, the most common of which were pneumonia (3.4%), dyspnea (2.7%), pyrexia (2%), mental status changes (1.4%), and respiratory failure (1.4%).
— Linda Mahjoubi (@lindamahj) November 5, 2018
Deaths due to AEs occurred in 2.7 percent of patients and included pneumonia (0.7%), myocardial infarction (0.7%), acute pulmonary edema (0.3%), embolism (0.3%), peripheral artery occlusion (0.3%), and respiratory distress (0.3%).
The FDA has granted Lorlatinib an accelerated approval for the treatment of ALK-positive metastatic non–small cell lung cancer. https://t.co/p7pQj98UMv
— Robinson Ortiz, MD (@RobinsonOrtizMD) November 3, 2018
Eight percent of patients permanently discontinuation treatment because of AEs. Approximately 48% of patients required dose interruptions and 24% required at least one dose reduction.
Source: Business Wire