Larotrectinib versus infigratinib for adult patients with both glioma and tyrosine kinase alterations after failure of initial therapies: Efficacy and safety analysis

Highlights

• Tyrosine kinase domains with genomic alterations have oncogenic potential.

• Higher efficacy for infigratinib than larotrectinib.

• Infigratinib has a higher overall survival than larotrectinib.

• Infigratinib has higher adverse effects than larotrectinib.

• Bevacizumab initial therapy has a higher overall survival.

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.

Keywords
Glioma; Hyperphosphatemia; Infigratinib; Larotrectinib; Tyrosine kinase alteration