Timing of brain metastases in relation to outcome during first-line ipilimumab plus nivolumab therapy for metastatic melanoma in a community oncology practice.

Abstract

Purpose: Patients with metastatic melanoma frequently develop brain metastases. Due to recent advances in melanoma therapy, we evaluated the timing of brain metastases diagnosis in relation to outcome during melanoma immunotherapy.

Methods: Patients who received 1st -line treatment with ipilimumab plus nivolumab for metastatic melanoma were identified via a database search. Patient characteristics and outcomes were recorded.

Results: Of 73 patients that met study criteria, 20 patients developed brain metastases (27.4%). Of these 20 patients, 14 had brain metastases at diagnosis of metastatic disease, Only 6 progressed in the brain following immunotherapy. All but one patient with brain metastases at diagnosis were symptomatic. Following immunotherapy, 4/15 (all with BRAF V600E mutations) achieved complete remissions and prolonged survival. Each of these patients was able to undergo elective treatment discontinuation. One additional patient developed stable disease. Delayed brain metastases proved to be infrequent (6/59 patients). Delayed brain metastases were always diagnosed within the first 15 months of treatment. Five of these 6 patients died, with a median progression-free survival of only 2.1 months.

Conclusion: Brain metastases frequently complicated the course of metastatic melanoma. Patients with symptomatic brain metastases at diagnosis had a potential for durable remissions following multidisciplinary treatment, particularly if a BRAF V600E mutation was present. This included 2 of 10 patients who were on steroid treatment prior to the start of immunotherapy. Treatment with combination immunotherapy seemed to reduce the development of subsequent brain metastases. Patients who developed delayed brain metastases had a very poor outlook, despite attempted salvage therapy.