CTNI-07. LONG-TERM EFFICACY AND SAFETY OF LAROTRECTINIB IN PATIENTS WITH TRK FUSION PRIMARY CENTRAL NERVOUS SYSTEM (CNS) TUMORS: AN UPDATED ANALYSIS
Bibliographic record
Abstract
Abstract BACKGROUND Larotrectinib is a highly selective TRK inhibitor approved for TRK fusion tumor-agnostic use. We report updated data on larotrectinib-treated patients with TRK fusion primary CNS tumors. METHODS Patients enrolled in 2 clinical trials (NCT02637687 [SCOUT], NCT02576431 [NAVIGATE]) were included. Responses were independent review committee (IRC)-assessed (RANO). Patients from SCOUT could stop larotrectinib in the absence of on-treatment progression (wait-and-see). Data cutoff: July 2023. RESULTS Fifty-five patients (38 aged <18 years at enrolment) were evaluated, including 16 with non-measurable disease at baseline. Tumor histologic groups included: high-grade glioma (HGG; n=32), low-grade glioma (LGG; n=15), and other (n=8). For all patients (n=55), ORR was 27% (95% CI 16-41): 3 CR, 12 PR, 24 SD (15 for >24 weeks), 12 PD, and 4 not evaluable. For pediatric patients (n=38), ORR was 37% (95% CI 22-54). ORR in patients with measurable disease only was 38% (95% CI 23-55) for all patients (n=39) and 52% (95% CI 32-71) for pediatric patients (n=27). The 24-week disease control rates were 55% (95% CI 41-68) and 74% (95% CI 57-87) for all patients and pediatric patients, respectively. Median time to response, DoR, PFS, and OS were 2, 12 (95% CI 6-not estimable [NE]), 12 (95% CI 7-20), and 38 months (95% CI 23-NE), respectively. Treatment duration ranged from 1 to 64+ months. At data cutoff, 1 pediatric patient with HGG and 4 with LGG entered wait-and-see; median duration of first wait-and-see period was 20 months (range 4-29). One pediatric patient with LGG resumed treatment following disease progression in wait-and-see. Treatment-related adverse events were predominantly Grade 1/2. CONCLUSION Larotrectinib demonstrated rapid, durable responses and manageable safety in patients with TRK fusion primary CNS tumors. This supports the adoption of NGS panels containing NTRK gene fusions when testing patients to identify those who might benefit from TRK inhibitor therapy.
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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 | 0.006 | 0.005 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.003 |
| Bibliometrics | 0.002 | 0.003 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 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".