Evaluation of prevalence and outcomes of serial tyrosine kinase inhibitor use in pediatric patients with advanced solid tumors

Purpose: Multitargeted tyrosine kinase inhibitors (mTKIs) are increasingly utilized in the treatment of pediatric sarcomas and other solid tumors. It is unknown whether serial treatment with multiple TKIs provides a benefit and which patients are most likely to benefit frommTKI rechallenge. Methods: We performed a retrospective cohort study of pediatric cancer patients who received serial mTKI therapy off-study between 2007 and 2020 as either monotherapy or combination therapy. We report patient characteristics, clinical outcomes, dosing patterns, and treatment-associated toxicity. Results: The study cohort included 25 patients. The overall prevalence of serial mTKI therapy among all patients treated for sarcoma at our institution was 3.7%, and the response rate to second mTKI was 9%. Median 6-month progression-free survival (PFS) and overall survival (OS) from start of second mTKI were 42.1% (95% CI: 20.4%62.5%) and 79.1% (95% CI: 57.0%-90.8%), respectively. Patients who had received 4 months or more (n = 11) of therapy with first mTKI had significantly longer PFS versus those who received less than 4 months (n = 11; p =.001). Thirty-three percent of patients discontinued second mTKI due to toxicity. Six (40%) of 15 patientswhodiscontinued the firstmTKI due to progression had either a partial response or stable disease on the second mTKI. Conclusions: We observed a low response rate tomTKI rechallenge. However, weidentified patients who had been treated with first mTKI for =4 months as more likely to have prolonged stable disease with second mTKI. Several patients had a response or stable disease on the second mTKIdespite having progressed on the firstmTKI. Though toxicity was common, only a minority of patients discontinued the second mTKI due to toxicity.