HGG-02. LONG-TERM EFFICACY AND SAFETY OF LAROTRECTINIB IN PEDIATRIC PATIENTS WITH TRK FUSION PRIMARY CENTRAL NERVOUS SYSTEM (CNS) TUMORS: AN UPDATED ANALYSIS
Bibliographic record
Abstract
Abstract BACKGROUND Larotrectinib is the first-in-class, highly selective TRK inhibitor approved for tumor-agnostic use in patients with TRK fusion cancer. We report data on larotrectinib-treated pediatric patients with TRK fusion primary CNS tumors. METHODS Patients aged <18 years with TRK fusion primary CNS tumors enrolled in two clinical trials (NCT02637687, NCT02576431) were included. Responses were independent review committee (IRC)-assessed per RANO. Patients were permitted to stop larotrectinib in the absence of on-treatment progression (wait-and-see) and remain on trial. RESULTS As of July 2023, 38 patients were eligible for efficacy analyses by IRC, including 11 patients with only non-measurable disease at baseline. Median age at enrollment was 7 years (range 0–17). Tumor histologic groups included: high-grade glioma (HGG; n=18), low-grade glioma (LGG; n=12), and other (n=8). Eleven (29%) patients had received ≥2 prior systemic therapies. Overall response rate was 37% (95% CI 22–54): three complete response, 11 partial response, 17 stable disease, five progressive disease, and two not evaluable. The 24-week disease control rate was 74% (95% CI 57–87). Medians for duration of response, progression-free survival, and overall survival (OS) were 17.2 months (95% CI 5.7–not estimable [NE]), 19.8 months (95% CI 11.1–50.8), and not reached (95% CI 32.7–NE), respectively. The 48-month OS rate was 60%. At data cutoff, one patient with HGG and four with LGG entered wait-and-see; median duration of the first wait-and-see period was 20.2 months (range 4–29). One patient with LGG resumed treatment following wait-and-see. Treatment-related adverse events (TRAEs) were predominantly Grade 1/2. No patients discontinued treatment due to TRAEs. CONCLUSION Larotrectinib demonstrated rapid, durable responses and a manageable safety profile in pediatric patients with TRK fusion primary CNS tumors. This supports the wider adoption of next-generation sequencing panels that include NTRK gene fusions when testing pediatric patients with CNS tumors.
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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 | 0.004 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".