Real-world data support a clinical benefit to the combination of dabrafenib (Tafinlar) and trametinib (Mekinist) in patients with BRAF V600-mutated metastatic melanoma with brain metastases. In an interim analysis of the COMBI-r study, median progression-free survival (PFS) in patients with brain metastases who were treated with the combination for at least 1 year was 6.1 months, reported researchers at the European Society for Medical Oncology Virtual Congress 2020.
Median PFS was superior in patients without brain metastases at 10.5 months, underscoring the high medical need of patients with brain metastases, noted the investigators, led by Carola Berking, MD, Department Head, Dermatology, University Clinic Erlangen, Germany.
The prospective COMBI-r study is evaluating the treatment of BRAF V600-mutated melanoma with the combination of dabrafenib plus trametinib in 58 German skin cancer centers. Effectiveness and safety were assessed in patients treated for at least 1 year or who had stopped treatment. A total of 273 patients had stage IV disease at baseline and were included in this analysis: 100 patients with brain metastases and 173 without brain metastases.
Best response was a complete response in 3.3% of patients with brain metastases and 10.3% of patients without brain metastases. The objective response rates were 31.9% and 44.5%, respectively, and 19.8% and 18.5% had progressive disease.
Median duration of therapy was 6.2 months in patients with brain metastases and 6.9 months in those without brain metastases. Median overall survival of patients with and without brain metastases was 11.6 months and 21.7 months, respectively.
A subjective assessment of tumor dynamics based on physician’s objective assessment of clinical parameters, including stage, lactate dehydrogenase level, and metastatic spread, showed that at baseline, 17% of patients without brain metastases had been assigned to slow tumor dynamics compared with 10% of patients with brain metastases. By the end of treatment, 21.4% of patients with brain metastases and 25.9% without brain metastases were assigned to slow tumor dynamics.
Patients with brain metastases more often used concomitant medications (45.0% vs 38.2%), including systemic corticosteroids (27.0% vs 9.8%) and antiepileptic drugs (7.0% vs 2.9%).
The most common adverse events in patients with brain metastases were pyrexia (19.0%), fatigue (19.0%), and nausea (17.0%). The rates of these adverse events were higher in patients without brain metastases—pyrexia, 31.2%; nausea, 28.3%; fatigue, 21.4%.
Scores on quality-of-life scales (EuroQual-5D, Functional Assessment of Chronic Illness Therapy-Fatigue, Functional Assessment of Cancer Therapy-General) improved from baseline in patients with and without brain metastases.
Source: Berking C, Livingstone E, Weichenthal M, et al. Real-world analysis of dabrafenib plus trametinib in patients with BRAFV600-mutated melanoma brain metastases – interim results of the non-interventional COMBI-r study. Ann Oncol. 2020;31:S755.