On July 14, 2022, the U.S. Food and Drug Administration (FDA) approved crizotinib (Xalkori) for adult and pediatric patients aged 1 year and older with unresectable, recurrent, or refractory inflammatory anaplastic lymphoma kinase (ALK)-positive myofibroblastic tumors.
The safety and efficacy of crizotinib were evaluated in two multicenter, single-arm, open-label trials that included 14 pediatric patients from trial ADVL0912 (ClinicalTrials.gov identifier NCT00939770) and 7 adult patients from trial A8081013 (NCT01121588) with unresectable, recurrent, or refractory ALK-positive myofibroblastic tumors.
The major efficacy outcome measure of these trials was objective response rate. Among the 14 pediatric patients, a total of 12 of the 14 patients (86%, 95% confidence interval [CI] = 57%–98%) experienced an objective response, assessed by an independent review committee. Among the seven adult patients, five had objective responses.
The most common adverse reactions (≥ 35%) in pediatric patients were vomiting, nausea, diarrhea, abdominal pain, rash, vision disorder, upper respiratory tract infection, cough, pyrexia, musculoskeletal pain, fatigue, edema, constipation, and headache. The most frequent adverse reactions (≥ 35%) in adult patients were vision disorders, nausea, and edema.
The recommended crizotinib 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.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. The application was granted Priority Review, and crizotinib received Orphan Drug designation.