ABSTRACT
Abstract Objectives To compare the efficacy and safety of larotrectinib with those of infigratinib in adult glioma patients with tyrosine kinase alterations. Methods Patients received oral infigratinib 125 mg (IN cohort, n = 125) or oral larotrectinib (LB cohort, n = 105) until unacceptable toxicity or disease progression. Results Duration of treatment was longer in the LB cohort than in the IN cohort (8 [9.5-6.25] months vs. 5.5 [6-5.25] months, p < 0.0001). Patients with partial responses (p = 0.0424) and overall survival (p = 0.03) were higher in the IN cohort than those in the LB cohort. The number of patients with disease progression was higher in the LB cohort (p = 0.0015). All the patients reported diarrhea, fatigue, vomiting, constipation, and decreased appetite. Patients in the IN cohort reported hyperphosphatemia, hyperlipasemia, stomatitis, dry skin, alopecia, dyspepsia, onycholysis, palmar-plantar erythrodysesthesia, nail disorders, and dry eyes. Patients in the LB cohort reported upper respiratory tract infections, pyrexia, cough, anemia, bacterial/viral infections, conjunctivitis, urinary tract infections, headaches, ataxia, dizziness, and muscle tremors. A total of 30 (24 %) and 40 (38 %) patients from the IN and the LB cohorts died at the follow-up of 18 months (p = 0.03). Patients who received bevacizumab initial therapy had higher overall survival (p = 0.048). Conclusions Infigratinib has higher efficacy and overall survival than larotrectinib but has higher adverse effects in the management of both glioma and tyrosine kinase alterations after failure of initial therapies. Initial bevacizumab therapy is associated with a higher overall survival.
ABSTRACT
Larotrectinib (also called LOxO-101, ARRY-470, and VITRAKVI?) is a kind of new high selective and broad-spectrum small molecule that is administered orally. Larotrectinib is tropomyosin receptor kinase (TRK) inhibitor and is used in the treatment of neuro-trophin tyrosine kinase receptor (NTRK) gene fusion in children and in adults. Based on use of larotrectinib against solid tumor in a vari-ety of NTRK gene fusion, larotrectinib has a good curative effect and security. On November 27, 2018, the drug was approved by the Food and Drug Administration (FDA) for the first time in the world. It is used in the treatment of no unknown drug resistant mutations, a broader shift, or partial surgical treatment, and after the treatment of disease progress of NTRK gene fusion in children and adult pa-tients with solid tumor. This article reviews the latest research progress in the research background, structure, and mechanism of ac-tion, clinical trials, adverse reactions and treatment, and drug resistance mechanism of larotrectinib.