Initial US Approval

20111

Indications

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. This indication is approved based on objective response rate (ORR) and duration of response (DOR) reported in pivotal studies.1

Recommended Dose/Route

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, PROFILE 1007 (NCT00932893)4

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. Participants in PROFILE 1007 included patients with ALK-positive metastatic NSCLC, previously treated with 1 platinum-based chemotherapy regimen.1

Treatment

Crizotinib 250 mg orally, twice daily, with or without food until disease progression or unacceptable toxicity occurs.1

Crizotinib: Efficacy Data

Crizotinib: Efficacy Data


Safety (Treatment Naïve, PROFILE 1014)

The most frequently reported adverse reactions (≥25%) of crizotinib in patients with NSCLC were vision disorders, nausea, diarrhea, vomiting, edema, constipation, elevated transaminases, fatigue, decreased appetite, upper respiratory infection, dizziness, and neuropathy.1 Serious adverse events (AEs) were reported in 34% of patients treated with crizotinib; the most frequent were dyspnea (4.1%) and pulmonary embolism (2.9%). Fatal adverse events occurred in 2.3% patients, consisting of septic shock, acute respiratory failure, and diabetic ketoacidosis.1

Dosage Reduction Due to AEs: 6%1

Permanent Discontinuation Due to AEs: 8%1

Safety (Previously Treated, PROFILE 1007)

Serious adverse reactions were reported in 37% of patients treated with crizotinib and 23% of patients in the chemotherapy arm.1 The most frequent serious adverse reactions reported in patients treated with crizotinib were pneumonia (4.1%), pulmonary embolism (3.5%), dyspnea (2.3%), and ILD (2.9%). Fatal adverse reactions in crizotinib-treated patients in PROFILE 1007 occurred in 5% of patients, consisting of acute respiratory distress syndrome, arrhythmia, dyspnea, pneumonia, pneumonitis, pulmonary embolism, ILD, respiratory failure, and sepsis. The most frequent AEs leading to dose reductions of crizotinib were increased ALT (8%), including some patients with concurrent increased AST, QTc prolongation (2.9%), and neutropenia (2.3%). The most frequent AEs that led to discontinuation of crizotinib were ILD (1.7%), increased ALT and AST (1.2%), dyspnea (1.2%), and pulmonary embolism (1.2%).1

Dosage Reduction Due to AEs: 16%1

Permanent Discontinuation Due to AEs: 15%1

References

  1. Xalkori (crizotinib). Package insert. Pfizer Inc; September 2023.
  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