Dabrafenib Plus Trametinib Promising in Melanoma
Patients with BRAF V600E melanoma and brain metastasis showed intracranial responses when receiving a BRAF (dabrafenib) and a MEK inhibitor (trametinib).
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Patients with BRAF V600E melanoma and brain metastasis showed intracranial responses when receiving a BRAF (dabrafenib) and a MEK inhibitor (trametinib), according to the first report from the COMBI-MB trial (ClinicalTrials.gov Identifier: NCT02039947) presented at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago.1
Presenter Michael A. Davies, MD, PhD, of the MD Anderson Cancer Center in Houston, Texas, noted that dabrafenib alone previously showed activity in this patient.
In the phase 2 COMBI-MB study, patients across 4 cohorts received the combination of dabrafenib and trametinib. Patients had BRAFV600E melanoma with asymptomatic brain metastasis and no prior local treatment (cohort A; 76 patients) or local prior treatment (cohort B; 16 patients). Cohorts C (16 patients) and D (17 patients) enrolled patients with BRAFV600D/E/K/R melanoma with asymptomatic or symptomatic brain metastasis regardless of prior local treatment.
The data discussion was focused on cohort A, in which the median age was 52 years, 53% of patients were male, 37% had lactate dehydrogenase greater than the upper limit of normal, and 54% had one brain lesion. Intracranial metastases were present in 89% of patients.
The median follow up was 9 months; 58% of patients had died; 41% were receiving ongoing treatment. For the primary endpoint, investigator-assessed intracranial response rate (IRR) was 58%; extracranial response rate (ERR) was 55%; objective response rate (ORR) was 58%.
Median durations of IRR, ERR, and OR were 6.5, 10.2, and 6.5 months, respectively.
Median progression-free survival was 5.6 months and 6-month overall survival was 79%. Median overall survival was 10.8 months.
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Although the primary endpoint was met, responses were less durable compared with patients with metastatic melanoma without brain metastases. “These results support the use of dabrafenib and trametinib as a treatment option for [melanoma] patients with brain metastases,” Dr Davies concluded.
Read more of Cancer Therapy Advisor's coverage of the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting by visiting the conference page.
- Davies MA, Robert C, Long GV, et al. COMBI-MB : A phase II study of combination dabrafenib (D) and trametini (T) in patients (pts) with BRAF V600-mutant (mut) melanoma brain metastases (MBM). J Clin Oncol. 2017;34(suppl; abstr 9506).