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CDRB436G2201 (low-grade glioma cohort)

Dabrafenib plus trametinib versus carboplatin plus vincristine in paediatric low-grade glioma with BRAF V600 mutations (phase 2)

Phase 2N = 110NCT02684058

Population
Paediatric patients with low-grade glioma with BRAF V600 mutations scheduled for first-line therapy; 110 randomised (73 dabrafenib plus trametinib, 37 chemotherapy)
Design
Randomised (2:1) phase 2 trial of dabrafenib plus trametinib versus standard chemotherapy (carboplatin plus vincristine) as first-line therapy; primary outcome independently assessed overall response (complete or partial response) by Response Assessment in Neuro-Oncology criteria; clinical benefit and progression-free survival also assessed
Primary endpoint
ORR
Arms
  • Dabrafenib plus trametinib (experimental, n = 73): Dabrafenib plus trametinib; doses not given in the abstract
  • Carboplatin plus vincristine (control, n = 37): Standard chemotherapy: carboplatin plus vincristine
People
Bouffet E
Δ ORR+36 pointsPFSHR 0.31 (95% CI 0.17–0.55)Δ median PFS+12.7 months
Show the numbers
Results reported for CDRB436G2201 (low-grade glioma cohort)
EndpointAnalysisDabrafenib plus trametinibCarboplatin plus vincristineEffect
ORRRandomised patients (n=110); analysis population not stated in the abstractIndependently assessed overall response (complete or partial) by RANO criteriaprimarymedian follow-up 18.9 monthsBouffet 202347%11%P<0.001Risk ratio 4.31 (95% CI 1.7 to 11.2), a ratio of response rates, not a hazard ratio.
PFSRandomised patients (n=110); analysis population not stated in the abstractProgression-free survival (assessed alongside the primary outcome)primaryBouffet 2023median 20.1 monthsmedian 7.4 monthsHR 0.31 (95% CI 0.17–0.55)P<0.001
Results reported for CDRB436G2201 (low-grade glioma cohort)
EndpointAnalysisDabrafenib plus trametinibCarboplatin plus vincristineEffect
ORRRandomised patients (n=110); analysis population not stated in the abstractIndependently assessed overall response (complete or partial) by RANO criteriaprimarymedian follow-up 18.9 monthsBouffet 202347%11%P<0.001Risk ratio 4.31 (95% CI 1.7 to 11.2), a ratio of response rates, not a hazard ratio.
PFSRandomised patients (n=110); analysis population not stated in the abstractProgression-free survival (assessed alongside the primary outcome)primaryBouffet 2023median 20.1 monthsmedian 7.4 monthsHR 0.31 (95% CI 0.17–0.55)P<0.001
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
PFS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
PFS0.310.17–0.55
Illustrative — modelled from reported values, not trial data. PFS, primary.
0%25%50%75%100%01020304050Months (modelled)
  • Dabrafenib plus trametinib (experimental)
  • Carboplatin plus vincristine (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
MonthsDabrafenib plus trametinibCarboplatin plus vincristine
0100.0%100.0%
1363.9%29.6%
2542.2%9.6%
3827.0%2.8%
5017.8%0.9%
Primary publication: Bouffet E, Hansford JR, Garrè ML, Hara J, Plant-Fox A, Aerts I, et al. Dabrafenib plus Trametinib in Pediatric Glioma with BRAF V600 Mutations. N Engl J Med. 2023;389(12):1108-1120. PubMedDOI

Appears in

Sources

  1. Bouffet E, Hansford JR, Garrè ML, Hara J, Plant-Fox A, Aerts I, et al. Dabrafenib plus Trametinib in Pediatric Glioma with BRAF V600 Mutations. N Engl J Med. 2023;389(12):1108-1120.

    PubMedDOI