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

Autor: Olsen HE; Boston Children's Hospital, Boston, Massachusetts, USA., Liu KX; Department of Radiation Oncology, Brigham and Women's Hospital/Dana-Farber Cancer Institute, Boston Children's Hospital, Boston, Massachusetts, USA., Frazier AL; Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts, USA., O'Neill AF; Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts, USA., Janeway KA; Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts, USA., DuBois SG; Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts, USA., Shulman DS; Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, Massachusetts, USA.
Jazyk: angličtina
Zdroj: Pediatric blood & cancer [Pediatr Blood Cancer] 2023 Nov; Vol. 70 (11), pp. e30652. Date of Electronic Publication: 2023 Aug 29.
DOI: 10.1002/pbc.30652
Abstrakt: 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.
(© 2023 Wiley Periodicals LLC.)
Databáze: MEDLINE
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