Anti-angiogenic TKIs in patients with advanced Ewing sarcoma: A systematic review and single-arm meta-analysis.
Bibliographic record
Abstract
11531 Background: The treatment of patients with localized Ewing Sarcoma (ES) is well established; however, strategies for relapsed disease remain uncertain. Encouraging outcomes have surfaced from early-phase trials assessing tyrosine kinase inhibitors (TKIs) with anti-angiogenic properties in this population. Hence, we conducted a systematic review and meta-analysis to synthesize current data on efficacy and safety of TKIs in patients with ES. Methods: We comprehensively searched PubMed, Embase, and Cochrane databases for clinical trials and cohort studies assessing anti-angiogenic TKIs in the treatment of advanced ES patients who had received at least one previous line of therapy. Main outcomes were objective response rate (ORR), disease control rate (DCR), median progression-free survival (PFS), and safety. Heterogeneity was assessed using I2 statistics. All analyses were conducted using R software (v.4.2.2), employing random effects models. Results: We included 10 studies: four phase II clinical trials and six retrospective cohort studies, comprising 191 patients. The following TKIs were evaluated: cabozantinib, regorafenib, apatinib, anlotinib and sorafenib. Median age in each study varied from 15 to 33 years, and 48.6% of patients had received ≥2 previous lines of therapy. In a pooled analysis of all ES patients treated with TKIs, the ORR was 30.1% (95%IC 16.3-43.8; I2=83.14%) and DCR was 66.8% (95%IC 59.4-73.5; I2=3.97%). In a comparative analysis stratified by drug, anlotinib was associated with an increased ORR (p<0.01) and no difference was seen in DCR among TKIs assessed (p=0.26). Seven studies evaluated TKIs in monotherapy, while the others included patients treated with TKIs + chemotherapy (CT); TKI+CT displayed higher ORR (p=0.04) and DCR (p=0.05), in a subgroup analysis by treatment strategies. The median PFS varied from 3.5 to 16.0 between drugs, and the overall median PFS was 4.4 months (95%CI 3.4-10). Dose reduction and interruption of treatment due to toxicity were reported in 39.6% and 6% of patients, respectively. Most common grade 3 or 4 adverse events were leukopenia (24.5%), anemia (8.8%), hypertension (5.6%), and diarrhea (4.3%). Conclusions: Anti-angiogenic TKIs are well tolerated and have shown anti-tumoral activity and clinical benefit in the treatment of patients with advanced Ewing sarcoma. Prospective randomized trials with adequate control groups are warranted to further evaluate the benefits of these agents. [Table: see text]
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.012 | 0.021 |
| Meta-epidemiology (narrow) | 0.003 | 0.001 |
| Meta-epidemiology (broad) | 0.018 | 0.039 |
| Bibliometrics | 0.007 | 0.007 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".