NCOG-05. HEALTH-RELATED QUALITY OF LIFE (HRQOL) IN THE PHASE 2 FIREFLY-1 (PNOC026) TRIAL OF THE TYPE II RAF INHIBITOR TOVORAFENIB IN RELAPSED/REFRACTORY (R/R) PEDIATRIC LOW-GRADE GLIOMA (PLGG)
Bibliographic record
Abstract
Abstract BACKGROUND Despite favorable long-term survival, ongoing disease and treatment-related morbidity substantially impact the HRQOL of patients with pLGG. Tovorafenib is a selective, CNS-penetrant, type II RAF inhibitor. Results from the ongoing FIREFLY-1 (NCT04775485) phase 2 study (Kilburn LK, et al. Nat Med. 2023) showed clinically meaningful responses and a manageable safety profile in pLGG. Vision remained stable or improved in 89% of evaluable patients with optic pathway gliomas (Nysom K, et al. Neuro-Oncol. 2023). METHODS FIREFLY-1 arm 1 patients 6 months–25 years of age with RAF-altered r/r pLGG received tovorafenib 420 mg/m2 weekly (600 mg max) in 28-day cycles. Exploratory measures included longitudinal assessment of PedsQL in patients ≥2 years of age. PedsQL 3.0 Cancer Module child self-reports Total Score and 8 subscales were used to assess HRQOL from 0 (worst)–100 (fewer problems/symptoms) (as of December 22, 2022) baseline (BL) to cycle 13 (C13) in patients ≥5 years of age. RESULTS For the PedsQL 3.0 Cancer Module, 51 completed self-reports at BL, and 32 at C13 due to continued attrition over time. Median Total Score was 81.5 (range: 46.3-100) at BL and 85.2 (range: 50-100) at C13. At C4, 16% worsened (decrease >10 points) and 11% improved (increase >10 points); by C13, 11% worsened and 33% improved. For Cognitive Problems, patients scored a median of 75 (range: 5-100) at BL and 85 (range: 20-100) at C13, with 11% and 26% improved at C4 and C13, respectively. A similar trend was seen with Nausea. Pain and Hurt remained even throughout (median: 87.5). Treatment Anxiety was not a major concern (median: 100, C1-C13); Procedural Anxiety improved over time (median: 58.3 BL; 79.2 at C13). CONCLUSIONS HRQOL generally remained stable, or improved, in the majority of patients with r/r pLGG during the first year of treatment with tovorafenib.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 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".