Initial US Approval

  • 20111

Indications

Metastatic ROS1/ALK+ NSCLC:

  • The treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors are anaplastic lymphoma kinase (ALK) or ROS1-positive as detected by an FDA-approved test.

Relapsed or Refractory ALK+ ALCL:

  • The treatment of pediatric patients 1 year of age and older and young adults with relapsed or refractory, systemic anaplastic large cell lymphoma (ALCL) that is ALK-positive.
    • Limitations of Use: The safety and efficacy of crizotinib have not been established in older adults with relapsed or refractory, systemic ALK-positive ALCL.

ALK+ IMT:

  • The treatment of adult and pediatric patients 1 year of age and older with unresectable, recurrent, or refractory inflammatory myofibroblastic tumor (IMT) that is ALK-positive.

Recommended Dose/Route

  • Crizotinib 250 mg orally, twice daily, with or without food1

Dose Reductions for Adverse Reactions

  • First-dose reduction: 200 mg twice daily1
  • Second-dose reduction: 250 mg once daily1
  • Permanently discontinue crizotinib capsules or pellets if unable to tolerate 250 mg taken once daily.1

Pivotal Study

PROFILE 1014 (NCT01154140)2,3

  • Treatment Setting: Previously untreated metastatic ALK+ NSCLC
  • Key Inclusion Criteria: Eligible participants in PROFILE 1014 included patients with ALK-positive metastatic NSCLC who had not received previous systemic treatment for advanced disease.
  • Treatment: Crizotinib 250 mg orally, twice daily, with or without food until disease progression or unacceptable toxicity occurs.

PROFILE 1007 (NCT00932893)4

  • Treatment Setting: Previously treated metastatic ALK+ NSCLC
  • Key Inclusion Criteria: Eligible participants in PROFILE 1007 included patients with ALK-positive metastatic NSCLC, previously treated with 1 platinum-based chemotherapy regimen.
  • Treatment: Crizotinib 250 mg orally, twice daily, with or without food until disease progression or unacceptable toxicity occurs.
Crizotinib: Efficacy Data

Crizotinib: Efficacy Data


Safety

PROFILE 1014 (Treatment Naive)2,3

  • Common Adverse Reactions (≥20%): The most frequently reported any grade AEs were vision disorders (71%), diarrhea (61%), vomiting (46%), edema (49%), constipation (43%), upper respiratory infection (32%), abdominal pain (26%), dysgeusia (26%), and headache (22%).
  • Common Laboratory Abnormalities (≥20%): The most frequently reported any grade laboratory abnormalities were increase ALT (79%), increased AST (66%), neutropenia (52%), lymphopenia (48%), and hypophosphatemia (32%).
  • Dosage Reduction Due to AEs: 6%
  • Permanent Discontinuation Due to AEs: 8%

PROFILE 1007 (Previously Treated)4

  • Common Adverse Reactions (≥20%): The most frequently reported any grade AEs were vision disorders (60%), diarrhea (60%), nausea (55%), vomiting (47%), constipation (42%), edema (31%), dysgeusia (26%), upper respiratory infections (26%), and dizziness (22%).
  • Common Laboratory Abnormalities (≥20%): The most frequently reported any grade laboratory abnormalities were increased ALT (76%), increased AST (61%), lymphopenia (51%), neutropenia (49%), and hypophosphatemia (28%).
  • Dosage Reduction Due to AEs: 16%
  • Permanent Discontinuation Due to AEs: 15%
Crizotinib: Most Common Adverse Events of Grade 3 or 4

Crizotinib: Most Common Adverse Events of Grade 3 or 4

References

  1. Xalkori (crizotinib). Prescribing information. Pfizer Inc; 2023. Accessed December 12, 2024. https://labeling.pfizer.com/ShowLabeling.aspx?id=676
  2. Solomon BJ, Mok T, Kim DW, et al. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med. 2014;371(23):2167-2177. doi:10.1056/NEJMoa1408440
  3. Solomon BJ, Kim DW, Wu YL, et al. Final overall survival analysis from a study comparing first-line crizotinib versus chemotherapy in ALK-mutation-positive non-small-cell lung cancer. J Clin Oncol. 2018;36(22):2251-2258. doi:10.1200/JCO.2017.77.4794
  4. Shaw AT, Kim DW, Nakagawa K, et al. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med. 2013;368(25):2385-2394. doi:10.1056/NEJMoa1214886
  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. Cappuzzo F, Moro-Sibilot D, Gautschi O, et al. Management of crizotinib therapy for ALK-rearranged non-small cell lung carcinoma: An expert consensus. Lung Cancer. 2015;87(2):89-95. doi:10.1016/j.lungcan.2014.12.010