On July 14, 2022, crizotinib was approved for adult and pediatric patients aged ≥ 1 year with unresectable, recurrent, or refractory ALK-positive inflammatory myofibroblastic tumors.1
Supporting Efficacy Data
Approval was based on findings in the multicenter studies ADVL0912 (ClinicalTrials.gov identifier NCT00939770) in pediatric patients and A8081013 (NCT01121588) in adult patients.
An objective response on independent review committee assessment was observed in 12 of 14 pediatric patients (86%, 95% confidence interval [CI] = 57%–98%), with a complete response in 5 (36%). Responses were ongoing at ≥ 6 and ≥ 12 months in seven responders.
An investigator-assessed objective response was observed in five of seven adult patients (71%), including a complete response in one. The duration of response was at least 6 months for all five responders and at least 12 months for two responders.
How It Is Used
In inflammatory myofibroblastic tumors, the recommended dose in adult patients is 250 mg orally twice daily until disease progression or unacceptable toxicity. The recommended pediatric dose is 280 mg/m2 orally twice daily until disease progression or unacceptable toxicity. Pediatric patients should receive standard antiemetic and antidiarrheal agents for gastrointestinal toxicities.
Among the 14 pediatric patients in the ADVL0912 study, the most common adverse events of any grade (≥ 35%) were vomiting (93%), nausea (86%), diarrhea (64%), upper respiratory tract infection (64%), cough (64%), abdominal pain (57%), rash (57%), vision disorders (50%), pyrexia (50%), musculoskeletal pain (43%), fatigue (43%), edema (36%), constipation (36%), and headache (36%). The most common grade 3 or 4 adverse events were diarrhea, edema, and hypotension (7% each). Serious adverse events occurred in 7%, most commonly neutropenia and hypotension (7% each). Adverse events led to treatment discontinuation in 29% of patients. The most common grade 3 or 4 laboratory abnormality was neutropenia (35%).
Among the seven adult patients in the A8081013 study, the most common adverse events of any grade (≥ 35%) were vision disorders, nausea, and edema. Product labeling states that the safety profile in this group was consistent with that in patients with ALK-positive or ROS1-positive non–small cell lung cancer.
Crizotinib has warnings/precautions for hepatotoxicity, including fatal cases; interstitial lung disease/pneumonitis; QT interval prolongation; bradycardia; severe visual loss; gastrointestinal toxicity in pediatric and young adult patients with anaplastic large cell lymphoma and pediatric patients with inflammatory myofibroblastic tumors; and embryofetal toxicity. Patients should be advised not to breastfeed while receiving crizotinib.
1. Xalkori (crizotinib) capsules prescribing information, Pfizer Inc, July 2022. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/202570s033lbl.pdf. Accessed August 4, 2022.