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Bending the Curve Trial by Trial
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ROAR

A Phase II, Open-label, Study in Subjects With BRAF V600E-Mutated Rare Cancers With Several Histologies to Investigate the Clinical Efficacy and Safety of the Combination Therapy of Dabrafenib and Trametinib

Phase 2N = 36NCT02034110

Population
BRAF V600E-mutant unresectable or metastatic anaplastic thyroid cancer (updated analysis: full cohort of 36; first report: 16 evaluable patients)
Design
Open-label, nonrandomised phase 2 basket study (Rare Oncology Agnostic Research, ROAR) of dabrafenib 150 mg twice daily plus trametinib 2 mg once daily until progression, unacceptable toxicity or death in BRAF V600E-mutant rare cancers; this record covers the anaplastic thyroid cancer cohort. Primary end point investigator-assessed overall response rate (RECIST 1.1 in the updated report); secondary end points duration of response, progression-free survival, overall survival and safety.
Primary endpoint
ORR
Arms
  • Dabrafenib plus trametinib (experimental, n = 36): Dabrafenib 150 mg orally twice daily plus trametinib 2 mg orally once daily
People
Subbiah V
Show the numbers
Results reported for ROAR
EndpointAnalysisDabrafenib plus trametinibControlEffect
ORREvaluable anaplastic thyroid cancer patients (16)interimSubbiah 201869% (41–89%)—Confirmed overall response rate 11 of 16, seven responses ongoing; median follow-up 47 weeks (range 4 to 120). All patients had prior radiation or surgery and six had prior systemic therapy. Investigator-assessed.
DOREvaluable anaplastic thyroid cancer patients (16)interimSubbiah 201890% at 12 mo—Median duration of response, progression-free survival and overall survival were not reached because of a lack of events; the figure is the 12-month estimate.
PFSEvaluable anaplastic thyroid cancer patients (16)interimSubbiah 201879% at 12 mo—Median not reached; 12-month estimate.
OSEvaluable anaplastic thyroid cancer patients (16)interimSubbiah 201880% at 12 mo—Median not reached; 12-month estimate.
ORRFull ROAR anaplastic thyroid cancer cohort (36 patients)long term-updatemedian follow-up 11.1 monthsSubbiah 202256% (38.1–72.1%)—Investigator-assessed per RECIST 1.1, including three complete responses. Median follow-up 11.1 months (range 0.9 to 76.6).
DORFull ROAR anaplastic thyroid cancer cohort (36 patients)long term-updateSubbiah 202250% at 12 mo—12-month duration-of-response rate.
PFSFull ROAR anaplastic thyroid cancer cohort (36 patients)long term-updateSubbiah 2022median 6.7 months; 43.2% at 12 mo——
OSFull ROAR anaplastic thyroid cancer cohort (36 patients)long term-updateSubbiah 2022median 14.5 months; 51.7% at 12 mo; 31.5% at 2 y——
Results reported for ROAR
EndpointAnalysisDabrafenib plus trametinibControlEffect
ORREvaluable anaplastic thyroid cancer patients (16)interimSubbiah 201869% (41–89%)—Confirmed overall response rate 11 of 16, seven responses ongoing; median follow-up 47 weeks (range 4 to 120). All patients had prior radiation or surgery and six had prior systemic therapy. Investigator-assessed.
DOREvaluable anaplastic thyroid cancer patients (16)interimSubbiah 201890% at 12 mo—Median duration of response, progression-free survival and overall survival were not reached because of a lack of events; the figure is the 12-month estimate.
PFSEvaluable anaplastic thyroid cancer patients (16)interimSubbiah 201879% at 12 mo—Median not reached; 12-month estimate.
OSEvaluable anaplastic thyroid cancer patients (16)interimSubbiah 201880% at 12 mo—Median not reached; 12-month estimate.
ORRFull ROAR anaplastic thyroid cancer cohort (36 patients)long term-updatemedian follow-up 11.1 monthsSubbiah 202256% (38.1–72.1%)—Investigator-assessed per RECIST 1.1, including three complete responses. Median follow-up 11.1 months (range 0.9 to 76.6).
DORFull ROAR anaplastic thyroid cancer cohort (36 patients)long term-updateSubbiah 202250% at 12 mo—12-month duration-of-response rate.
PFSFull ROAR anaplastic thyroid cancer cohort (36 patients)long term-updateSubbiah 2022median 6.7 months; 43.2% at 12 mo——
OSFull ROAR anaplastic thyroid cancer cohort (36 patients)long term-updateSubbiah 2022median 14.5 months; 51.7% at 12 mo; 31.5% at 2 y——
Illustrative — modelled from reported values, not trial data. PFS, long term-update.
0%25%50%75%100%051015Months (modelled)
  • Dabrafenib plus trametinib (experimental)

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

Data table (modelled values)
MonthsDabrafenib plus trametinib
0100.0%
466.1%
843.7%
1326.1%
1717.2%
Illustrative — modelled from reported values, not trial data. OS, long term-update.
0%25%50%75%100%0510152025Months (modelled)
  • Dabrafenib plus trametinib (experimental)
Data table (modelled values)
MonthsDabrafenib plus trametinib
0100.0%
674.1%
1349.0%
1938.5%
2631.5%
Primary publication: Subbiah V, Kreitman RJ, Wainberg ZA, Cho JY, Schellens JHM, Soria JC, et al. Dabrafenib and Trametinib Treatment in Patients With Locally Advanced or Metastatic BRAF V600-Mutant Anaplastic Thyroid Cancer. J Clin Oncol. 2018;36(1):7-13. PubMedDOI

Appears in

Sources

  1. Subbiah V, Kreitman RJ, Wainberg ZA, Cho JY, Schellens JHM, Soria JC, et al. Dabrafenib and Trametinib Treatment in Patients With Locally Advanced or Metastatic BRAF V600-Mutant Anaplastic Thyroid Cancer. J Clin Oncol. 2018;36(1):7-13.

    PubMedDOI

  2. Subbiah V, Kreitman RJ, Wainberg ZA, Cho JY, Schellens JHM, Soria JC, et al. Dabrafenib plus trametinib in patients with BRAF V600E-mutant anaplastic thyroid cancer: updated analysis from the phase II ROAR basket study. Ann Oncol. 2022;33(4):406-415.

    PubMedDOI