TADPOLE (CDRB436G2201)
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.
Overview
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.
- 47 vs 11 out of 100 had their tumour shrink with Dabrafenib + trametinib compared with Carboplatin + vincristine; 36 more per 100.
- Roughly one extra person helped for every 3 treated. That is a rough figure taken from the two percentages, not a guarantee for any one person.
- The p-value (<0.001) says a difference this large would rarely happen by chance; it does not say how large or how useful the difference is.
- A response rate counts how many people had their tumours shrink by a set amount; shrinking is encouraging but does not by itself show that people live longer or feel better.
- Median 20.1 vs 7.4 months with Dabrafenib + trametinib compared with Carboplatin + vincristine; about 12.7 months longer for half the group.
- A median is a midpoint: half the people did better than this and half did worse, so it is not a prediction for any one person.
- Put another way, the treated group had about 69 percent lower chance of the event at any given time (hazard ratio 0.31, likely range 0.17 to 0.55).
- This is a surrogate endpoint: it measures the cancer being controlled or absent on scans and tests, which often, but not always, translates into living longer.
- These results apply to the people the trial enrolled: Newly diagnosed BRAF V600-mutant paediatric low-grade glioma needing systemic therapy: dabrafenib + trametinib vs carboplatin + vincristine (2:1 randomisation). People in a different situation may not see the same effect.
- The trial selected people by a biomarker (BRAF); the result should not be assumed for people whose cancer does not have it.
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 participants enrolled.
| 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 (0.17–0.55) | <0.001 | link |
| Carboplatin + vincristine | 37 | 7.4 months |
Pages like this
not linked directly; found by shared links- TrialFIREFLY-1
Shares RACE for Children Act, Paediatric low-grade glioma, BRAF, RAS / RAF / MEK / ERK (MAPK) and the tags nci-coverage, paediatric, cns.
- CancerCraniopharyngioma
Shares Dabrafenib + trametinib, Paediatric low-grade glioma, BRAF, RAS / RAF / MEK / ERK (MAPK) and the tags nci-coverage, paediatric, cns.
- CancerEpendymoma
Shares Paediatric low-grade glioma, Vincristine, Carboplatin and the tags nci-coverage, paediatric, cns.
- TrialACTION
Shares RACE for Children Act and the tags nci-coverage, paediatric, cns.
- CancerDiffuse midline glioma, H3 K27-altered (including DIPG)
Shares RACE for Children Act, Paediatric low-grade glioma and the tags nci-coverage, paediatric, cns.
- CancerAtypical teratoid/rhabdoid tumour (ATRT)
Shares Vincristine, Carboplatin and the tags nci-coverage, paediatric, cns.
- InstitutionACCELERATE
Shares RACE for Children Act, Paediatric low-grade glioma and the tags nci-coverage, paediatric.
- InstitutionInnovative Therapies for Children with Cancer (ITCC)
Shares RACE for Children Act, Paediatric low-grade glioma and the tags nci-coverage, paediatric.