{"doi":"10.1002/pbc.30652","title":"Evaluation of prevalence and outcomes of serial tyrosine kinase inhibitor use in pediatric patients with advanced solid tumors","abstract":"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 from mTKI 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 patients who discontinued the first mTKI due to progression had either a partial response or stable disease on the second mTKI. CONCLUSIONS: We observed a low response rate to mTKI rechallenge. However, we identified 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 mTKI despite having progressed on the first mTKI. Though toxicity was common, only a minority of patients discontinued the second mTKI due to toxicity.","journal":"Pediatric Blood & Cancer","year":2023,"id":410923,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9512,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":257989,"name":"Kevin X. Liu","orcid":"0000-0003-2071-5137","position":1,"is_corresponding":false},{"id":7907,"name":"A. Lindsay Frazier","orcid":"0000-0003-4748-8552","position":2,"is_corresponding":false},{"id":36114,"name":"Allison F. O’Neill","orcid":"0000-0002-8957-3870","position":3,"is_corresponding":false},{"id":346979,"name":"Katherine A. Janeway","orcid":"0000-0001-6000-3594","position":4,"is_corresponding":false},{"id":305844,"name":"Steven G. DuBois","orcid":"0000-0003-0882-738X","position":5,"is_corresponding":false},{"id":392175,"name":"David S. Shulman","orcid":"0000-0002-5994-2604","position":6,"is_corresponding":false},{"id":390315,"name":"Hannah E. Olsen","orcid":"0000-0002-4804-5684","position":0,"is_corresponding":true}],"reference_count":13,"raw_metadata":null,"created_at":"2026-07-19T01:21:38.940853Z","pmid":"37644664","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}