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The first randomised trial to show that a targeted drug pair beats chemotherapy in children with a brain tumour. Children whose low-grade glioma carries a BRAF V600 mutation had far more tumour shrinkage and a much longer time before progression on dabrafenib plus trametinib than on standard carboplatin and vincristine.
Phase 2 randomised trial (Bouffet et al., NEJM 2023). 110 patients randomised (73 to dabrafenib plus trametinib, 37 to carboplatin plus vincristine). At a median follow-up of 18.9 months the independently assessed overall response rate was 47% versus 11% (risk ratio 4.31; 95% CI 1.7 to 11.2), clinical benefit 86% versus 46%, and median progression-free survival 20.1 versus 7.4 months (HR 0.31; 95% CI 0.17 to 0.55). Grade 3 or higher adverse events were less frequent with the targeted pair (47% versus 94%). Basis of the FDA approval of dabrafenib plus trametinib for paediatric BRAF V600E LGG in March 2023, with new liquid and dispersible formulations for young children. A separate cohort in relapsed BRAF V600 high-grade glioma also responded.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
110 randomised.
| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Overall response rate (independent review, RANO)primary | Dabrafenib + trametinib | 73 | 47% | - | <0.001 | link |
| Carboplatin + vincristine | 37 | 11% | ||||
| Progression-free survival | Dabrafenib + trametinib | 73 | 20.1 months | 0.31 (0.17 to 0.55) | <0.001 | link |
| Carboplatin + vincristine | 37 | 7.4 months |
Shares RACE for Children Act, Paediatric low-grade glioma, Paediatric oncology roadmap: cooperative-group cures → engineered immunity → drugs developed for children first, BRAF and the tags paediatric, cns.
Shares RACE for Children Act, Paediatric oncology roadmap: cooperative-group cures → engineered immunity → drugs developed for children first and the tags paediatric, cns.
Shares Dabrafenib + trametinib, Paediatric low-grade glioma, BRAF, RAS / RAF / MEK / ERK (MAPK) and the tags paediatric, cns.
Shares Paediatric low-grade glioma, Vincristine, Carboplatin and the tags paediatric, cns.
Shares RACE for Children Act, Paediatric low-grade glioma, Paediatric oncology roadmap: cooperative-group cures → engineered immunity → drugs developed for children first and the tags paediatric, cns.
Shares Vincristine, Carboplatin and the tags paediatric, cns.
Shares Vincristine, Carboplatin and the tags paediatric, cns.
Shares Paediatric oncology roadmap: cooperative-group cures → engineered immunity → drugs developed for children first, Vincristine and the tags paediatric, cns.