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

Lorlatinib: Efficacy Data


Safety (Treatment Naïve, CROWN)

  • Common Adverse Reactions: The most frequently reported any grade AEs 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%).1,2
  • 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 AEs: 49%1
  • Dosage Reduction Due to AEs: 21%1
  • Permanent Discontinuation Due to AEs: 6.7%1

Safety (Previously Treated, B7461001)

  • Common Adverse Reactions (≥20%): The most frequently reported any grade AEs observed among patients receiving lorlatinib were edema (57%), peripheral neuropathy (47%), cognitive effects (27%), dyspnea (27%), fatigue (26%), weight gain (24%), arthralgia (23%), mood effects (23%), and diarrhea (22%).1
  • Common Lab Abnormalities (≥24%): The most frequently reported laboratory abnormalities were hypercholesterolemia (96%), hypertriglyceridemia (90%), anemia (52%), hyperglycemia (52%), increased AST (37%), hypoalbuminemia (33%), increased ALT (28%), increased lipase (24%), and increased alkaline phosphatase (24%).1
  • 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. https://labeling.pfizer.com/ShowLabeling.aspx?id=11140
  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