Table 1 Summary of the findings of the studies assessing the efficacy and safety of TKIs in ewing sarcoma
From: Tyrosine kinase inhibitors in Ewing’s sarcoma: a systematic review
Reference. | Intervetion, number of Ewing sarcoma patients if applicable | Indication | Outcome |
|---|---|---|---|
PHASE I Clinical trials | |||
Chuk et al., 2018 [59] | Cab, 4 | Recurrent Ewing’s sarcoma | 1 patient had prolonged SD AEs: 27% had dose-limiting toxicities One patient suffered from a grade 4 AE then died due to multi-organ failure |
Casanova et al., 2023 [66] | Reg + vin + Irinotecan, 5 | Recurrent Ewing’s sarcoma | PR: 40% SD: 60% AEs: All patients experienced at least a grade 1 AE 38% experienced serious AEs |
Daw et al., 2005 [80] | Gef, 1 | Recurrent Ewing’s sarcoma | Best response was PR AEs: 7 grade 3 AEs and one grade 4 AE were reported |
Jimeno et al., 2007 [81] | Gef, 1 | Recurrent Ewing’s sarcoma | Best response was PR Treatment was well tolerated |
Furman et al., 2009 [82] | Gef + irino, 3 | Recurrent Ewing sarcoma family of tumors | PR: 33.3% SD: 33.3% AEs: 31% of patients had a grade 3–4 dose-limiting toxicity |
Geller et al., 2018 [74] | Axi, 3 | Recurrent Ewing’s sarcoma/Primitive Neuroectodermal Tumor | One patient had SD for more than 6 cycles as best response AEs: 18.75% of patients had grade 3 AEs and no grade 4 AEs were reported |
Fox et al., 2010 [76] | Ced, 3 | Recurrent Ewing’s sarcoma family tumors | One patient had a PR complicated by a bilateral asymptomatic pneumothorax |
Dela Cruz et al., 2020 [78] | Lenv + Ever | Pediatric solid tumors including Ewing sarcoma | All patients had AEs, with 47.1% having grade 3–4 AEs |
PHASE II Clinical trials | |||
Bond et al., 2008 [85] | Imat, 26 | Recurrent Ewing’s sarcoma | Only 1 PR recorded |
Chugh et al., 2009 [86] | Imat, 13 | Advanced Ewing’s sarcoma | m-PFS: 1.68 months ORR: 0.0% No CBR and 13 PD |
Chao et al., 2010 [87] | Imat, 5 | Reccurent Ewing sarcoma family tumors | m-PFS: 1 month m-OS: 6 months 1 PR was seen in the patient with the most elevated levels of PDGFRα and KIT expression AEs: 28.5% of patients had grade 3 AEs and 14.28% had a grade 4 AE |
Duffaud et al., 2023 [64] | Reg, 36 | Recurrent Ewing’s sarcoma | m-PFS: 2.66 months 8 weeks-PFS: 56% AEs: 56% of patients in the Reg arm experienced serious AEs One patient died in the Reg arm |
Attia et al., 2023 [65] | Reg, 30 | Advanced Ewing’s sarcoma family of tumors | m-PFS: 3.45 months m-OS: 12.36 months 8 weeks-PFR: 63% RECIST 1.1: 100% AEs: 18 grade 3 AEs and one grade 4 AE were reported One death unrelated to treatment |
Retrospective studies | |||
Kokkali et al., 2023 [61] | Cab, 5 | Advanced Ewing’s sarcoma/ Primitive Neuroectodermal Tumor | m-PFS: 5.7 months 3 months-PFS: 80% 6 months-PFS: 40% m-OS: 8 months AEs: 75% had at least one AE with almost all being grade 1–3 12.5% had serious AEs noted: PNET of the adrenal gland and lung metastases presented with unilateral hemothorax |
Raciborska et al., 2018 [70] | Sor, 2 | Recurrent Ewing’s sarcoma | 5-years OS (whole groupe):64.49% ORR (whole groupe): 75% One patient had PD and the other one had PR AEs: 25% had grade 3 skin toxicities |
Bodea et al., 2022 [71] | Bev and Sor and Cycl, 14 | Recurrent Ewing’s sarcoma | 11 patients achieved stable disease or better as best response including one patient with CR and one patient with PR AEs: 94.8% of patients had grade 3 or more AEs |
Xie et al., 2018 [52] | Apat and ever or apat alone, 10 | Advanced Ewing’s sarcoma | m-PFS: 2 months 12 weeks-PFS: 22.5% ORR: 70% Best response was PR median duration of response: 2 months AEs: 100% of patients had AEs 46.5% had grade 3–4 AEs One patient died Toxicity profile more severe than expected |
Wang et al., 2018 [53] | Apat, 11 | Advanced Ewing’s sarcoma | m-PFS: 16 months 6 months-PFS: 81.8% 12 months-PFS: 71.6% ORR:40.00% DCR: 80.00% Best response was PR AEs: Most AEs were grade 1–2 10% of patients had grade 3 AEs (hand-foot syndrome) 20% died of lung metastasis due to respiratory failure |
Seto et al., 2019 [67] | Pazo, 3 | Advanced Ewing’s sarcoma | 2 SD and 1 PD |
Liu et al., 2021 [62] | Anlo, 8 | Advanced Ewing’s sarcoma | m-PFS: 6.7 months 3 months-PFS: 75% 6 months-PFS: 50% ORR: 37.5% PR, SD and PD were 37.5%, 37.5% and 25% respectively. AEs: 92% of patients had a at least one grade 1 AE Seven grade 3–4 AEs were reported |
Soroka et al., 2023[57] | Reg, 18 | Recurrent Ewing’s sarcoma | m-PFS: 3.9 months m-OS: 13.4 months CBR: 100% PR: 100% CR: 0% AEs: 24% of patients had grade 3 or higher AEs |
Prospective Studies | |||
Dong et al., 2021[57] | Anlo + Irino + Vinc, 35 | Advanced Ewing’s sarcoma | m-PFS: 5.73 m-OS: 7.56 CR (pediatric): 33.3% PR: 55.5% Treatments produced tolerable toxicity |