CTNI-75. EFFICACY AND SAFETY OF LAROTRECTINIB IN PATIENTS WITH TROPOMYOSIN RECEPTOR KINASE (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 tumor-agnostic use in patients with various tumor types, including primary CNS tumors. Here, we report the independent central review and updated data on patients with TRK fusion-positive primary CNS tumors. METHODS Patients with TRK fusion primary CNS tumors enrolled in two clinical trials (NCT02637687, NCT02576431) were included. Responses were independent review committee (IRC)-assessed. RESULTS As of July 2022, 41 patients were eligible for response assessment by IRC. The median age at enrollment was 11 years (range 1-79). Tumor histologic groups included: high-grade glioma (HGG; n=25), low-grade glioma (LGG; n=9), and other (n=7). Sixteen (39%) patients had received ≥ 2 prior systemic therapies. For all patients, objective response rate (ORR) was 22% (95% CI 11–38): one complete response, eight partial response, 20 stable disease, and 12 progressive disease. For pediatric patients (n=28), the ORR was 29% (95% CI 13–49). For pediatric patients with HGG and LGG, ORRs were 14% (95% CI 2–43) and 57% (95% CI 18–90), respectively. The disease control rates at 24 weeks were 54% (95% CI 37–69) and 71% (95% CI 51–87) for all patients and pediatric patients, respectively. Medians for time to response, duration of response, progression-free survival, and overall survival (OS) were 1.9 months, 12.2 months (95% CI 3.7–not estimable), 11.1 months (95% CI 3.6–19.8), and not reached, respectively. The 48-month OS rate was 52%. Treatment duration ranged from 1 to 50+ months. Treatment-related adverse events (TRAEs) were mostly Grade 1/2. No patients discontinued treatment due to TRAEs. CONCLUSION Larotrectinib demonstrated rapid, durable responses and a manageable safety profile in patients with TRK fusion primary CNS tumors. This supports the wider adoption of next-generation sequencing panels that include NTRK gene fusions when testing patients with CNS tumors.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".