Melanoma patients with brain metastases may benefit from two combination regimens used to treat patients who have metastatic melanoma but no brain metastases, according to the early results of ongoing multicenter clinical trials led by investigators from The University of Texas MD Anderson Cancer Center.
The CheckMate-204 and COMBI-MB trials are investigating an immunotherapy combination and a targeted therapy combination, respectively, in patients with melanoma brain metastases, a patient group traditionally excluded from clinical trials. So far, more than 50% of the patients in each trial have had significant tumor shrinkage.
“These encouraging results highlight the possibility of new treatment options, and new hope, for our patients with metastases to the brain, which are a leading cause of death from melanoma,” said Hussein Tawbi, M.D., Ph.D., an associate professor in the Department of Melanoma Medical Oncology and MD Anderson’s principal investigator of the CheckMate-204 trial.
Patients in the phase II CheckMate-204 trial (No. 2015-0696) are treated with the immune checkpoint inhibitors ipilimumab, which blocks CTLA-4 (cytotoxic T-lymphocyte-associated protein 4), and nivolumab, which inhibits PD-1 (programmed cell death protein 1). Of the 75 patients evaluated thus far, 41 (54%) had significant brain metastasis shrinkage, including 16 who had a complete response. After 9 months of follow-up, only one of the 41 responders had disease progression. The trial is still enrolling patients who are symptomatic or require steroids.
All patients in the phase II COMBI-MB trial (No. 2013-1020) have metastatic melanoma with a BRAF V600 mutation and receive dabrafenib, which targets mutant BRAF V600 kinases, and trametinib, which inhibits MEK1 and MEK2. For analysis, patients were grouped according to their specific BRAF mutation, their Eastern Cooperative Oncology Group performance status, whether they had received previous treatment for brain metastases, and whether their brain metastasis symptoms were controlled. In the largest of these groups—comprising 76 patients with BRAF V600E mutations, performance status of 1 or 2, no prior treatment, and controlled symptoms—44 patients (58%) had significant tumor shrinkage, and four of these patients had a complete response. Similar results were observed in the other three groups. The trial is ongoing but is no longer recruiting patients.
“In addition to showing that these combinations are safe and effective, these results demonstrate the feasibility of conducting clinical trials for melanoma patients with brain metastases. This will ultimately make more treatments available to these patients,” said Michael Davies, M.D., Ph.D., an associate professor in the Department of Melanoma Medical Oncology and MD Anderson’s principal investigator of the COMBI-MB trial.
The preliminary results of both trials were presented at the 2017 American Society of Clinical Oncology Annual Meeting in June. The preliminary results of the COMBI-MB trial were also published in Lancet Oncology in July.
OncoLog, November-December 2017, Volume 62, Issue 11-12