Initial US Approval
20181
Indications
Treatment of adult patients with metastatic non–small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK)-positive as detected by an FDA-approved test. This indication is approved based on objective response rate (ORR) and duration of response (DOR) reported in pivotal studies.1
Recommended Dose/Route
100 mg orally, once daily, with or without food1
Dose Reductions for Adverse Reactions
First dose reduction: 75 mg orally once daily1
Second dose reduction: 50 mg orally once daily1
Permanently discontinue lorlatinib in patients who are unable to tolerate 50 mg orally once daily.1
Pivotal Study
CROWN (NCT03052608)2,3, B7461001 (NCT01970865)4
Key Inclusion Criteria: Eligible participants in CROWN included patients with ALK-positive metastatic NSCLC who had not received previous systemic treatment for advanced disease. Participants in B7461001 included patients with ALK-positive metastatic NSCLC, previously treated with one or more ALK kinase inhibitors and an ECOG performance status of 0 to 2.1
Treatment
Lorlatinib 250 mg orally, twice daily, with or without food until disease progression or unacceptable toxicity occurs.1
Lorlatinib: Efficacy Data
Safety (Treatment Naïve, CROWN)
The most common adverse events (AEs) of any grade with lorlatinib were hypercholesterolemia (70%), hypertriglyceridemia (64%), edema (55%), increased weight (38%), peripheral neuropathy (34%), cognitive effects (21%), anemia (19%), hypertension (18%), mood effects (16%), and hyperlipidemia (11%). Serious adverse reactions occurred in 34% of patients; the most common were pneumonia (4.7%), dyspnea (2.7%), respiratory failure (2.7%), cognitive effects (2.0%), and pyrexia (2.0%). Fatal adverse reactions occurred in 3.4% of patients treated with lorlatinib and included pneumonia (0.7%), respiratory failure (0.7%), cardiac failure acute (0.7%), pulmonary embolism (0.7%), and sudden death (0.7%).1,2
Dosage Interruption Due to AEs1: 49%
Dosage Reduction Due to AEs1: 21%
Permanent Discontinuation Due to AEs1: 6.7%
Safety (Previously Treated, B7461001)
The most frequent (≥20%) AEs observed among patients receiving lorlatinib were edema, peripheral neuropathy, cognitive effects, dyspnea, fatigue, weight gain, arthralgia, mood effects, and diarrhea.1 The most common altered laboratory values reported in patients receiving lorlatinib were hypercholesterolemia, hypertriglyceridemia, anemia, hyperglycemia, increased AST, hypoalbuminemia, increased ALT, increased lipase, and increased alkaline phosphatase. Serious AEs occurred in 32% of the 295 patients; the most common were pneumonia (3.4%), dyspnea (2.7%), pyrexia (2%), mental status changes (1.4%), and respiratory failure (1.4%). Fatal AEs occurred in 2.7% 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 most frequent AEs leading to dose interruptions were edema (7%), hypertriglyceridemia (6%), peripheral neuropathy (5%), cognitive effects (4.4%), increased lipase (3.7%), hypercholesterolemia (3.4%), mood effects (3.1%), dyspnea (2.7%), pneumonia (2.7%), and hypertension (2.0%). The most frequent AEs that led to dose reductions were edema (6%), peripheral neuropathy (4.7%), cognitive effects (4.1%), and mood effects (3.1%). The most frequent AEs that led to permanent discontinuation of lorlatinib were respiratory failure (1.4%), dyspnea (0.7%), myocardial infarction (0.7%), cognitive effects (0.7%) and mood effects (0.7%).1
Dosage Interruption Due to AEs: 48%1
Dosage Reduction Due to AEs: 24%1
Permanent Discontinuation Due to AEs: 8%1
References
1. Lorbrena (lorlatinib). Package insert. Pfizer Inc; April 2023.
2. Shaw AT, Bauer TM, de Marinis F, et al. First-Line Lorlatinib or crizotinib in advanced ALK-positive lung cancer. N Engl J Med. 2020;383(21):2018-2029. doi:10.1056/NEJMoa2027187
3. Solomon BJ, Bauer TM, Mok TSK, et al. Efficacy and safety of first-line lorlatinib versus crizotinib in patients with advanced, ALK-positive non-small-cell lung cancer: updated analysis of data from the phase 3, randomised, open-label CROWN study. Lancet Respir Med. 2023;11(4):354-366. doi:10.1016/S2213-2600(22)00437-4
4. Solomon BJ, Besse B, Bauer TM, et al. Lorlatinib in patients with ALK-positive non-small-cell lung cancer: results from a global phase 2 study. Lancet Oncol. 2018;19(12):1654-1667. doi:10.1016/S1470-2045(18)30649-1