Initial US Approval

  • 20181

Indications

Metastatic ALK+ NSCLC:

  • The 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.1

Recommended Dose/Route

  • Lorlatinib 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

  • Treatment Setting: Previously untreated metastatic ALK+ NSCLC
  • Key Inclusion Criteria: Eligible participants in CROWN included patients with ALK-positive metastatic NSCLC who had not received previous systemic treatment for advanced disease with an ECOG status of 0-2..
  • Treatment: Lorlatinib 100 mg orally, twice daily, with or without food until disease progression or unacceptable toxicity occurs.1

B7461001 (NCT01970865)4

  • Treatment Setting: Previously treated metastatic ALK+ NSCLC
  • Key Inclusion Criteria: Eligible 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.
  • Treatment: Lorlatinib 100 mg orally, twice daily, with or without food until disease progression or unacceptable toxicity occurs.
Lorlatinib: Efficacy Data

Lorlatinib: Efficacy Data


Safety

CROWN (Treatment Naïve)1-3

  • 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%), diarrhea (21%), and dyspnea (20%).
  • Common Laboratory Abnormalities (≥10%): The most frequently reported any grade laboratory abnormalities were anemia (19%), increased ALT (17%), increased gamma glutamyl transferase (15%), AST (14%), and increased creatine phosphokinase (11%).
  • Dosage Interruption Due to AEs: 49%
  • Dosage Reduction Due to AEs: 21%
  • Permanent Discontinuation Due to AEs: 6.7%

B7461001 (Previously Treated)1,4 

  • 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%).
  • Common Lab Abnormalities (≥20%): 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%), increased alkaline phosphatase (24%), thrombocytopenia (23%), increased amylase (22%), lymphopenia (22%), hypophosphatemia (21%), hyperkalemia (21%), and hypomagnesemia (21%).
  • Dosage Interruption Due to AEs: 48%
  • Dosage Reduction Due to AEs: 24%
  • Permanent Discontinuation Due to AEs: 8%
Lorlatinib: Most Common Adverse Events of Grade 3 or 4

Lorlatinib: Most Common Adverse Events of Grade 3 or 4

References

  1. Lorbrena (lorlatinib). Prescribing information. 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
  5. Dziadziuszko R, Peters S, Ruf T, et al. Clinical experience and management of adverse events in patients with advanced ALK-positive non-small-cell lung cancer receiving alectinib. ESMO Open. 2022;7(6):100612. doi:10.1016/j.esmoop.2022.100612
  6. Zhou F, Yang Y, Zhang L, et al. Expert consensus of management of adverse drug reactions with anaplastic lymphoma kinase tyrosine kinase inhibitors. ESMO Open. 2023;8(3):101560. doi:10.1016/j.esmoop.2023.101560
  7. Liu G, Mazieres J, Stratmann J, et al. A pragmatic guide for management of adverse events associated with lorlatinib. Lung Cancer. 2024;191:107535. doi:10.1016/j.lungcan.2024.107535