The risk of brain metastases (BM) in advanced melanoma (MM) is 40-50%. Historical median survival of MM patients (pts) with BMs was 4-5 months. Current systemic treatments with targeted therapy and immunotherapy prolong survival up to > 2 years, while prognosis of BMs carrying pts is not fully defined and optimal treatment sequencing remain unknown. We aimed to analyze the contemporary treatment outcomes in this specific group of pts.
Clinical data, course of treatment and clinical outcomes of 376 subsequent stage IV melanoma patients with BMs treated in one reference institution in period 2000-2018 were analyzed retrospectively (39% of BMs pts diagnosed before 2014).
Median age for BMS diagnosis was 61, 171 pts were BRAF+ and 118 - wild-type. Median time to BMs from melanoma diagnosis was 2.3 years (8% had BMs at diagnosis). In 1st line BRAF(-) pts were treated with anti-PD-1 in 36%, chemotherapy - 46%, while BRAF(+) pts – with BRAFi/MEKi - 68% and anti-PD-1 - 5%. For the whole group median overall survival (mOS) of BRAF(+) was 7 months, while mOS BRAF(-) - 4 m. mOS for patients treated initially with BRAFi/MEKi was 9 m, while for anti-PD1 - 15 m (but it may be related to less advanced cases preferred for immunotherapy). BMs treatment modality chosen primarily was neurosurgery in 78 (21%) pts, radiotherapy - 270 (72%) with increasing use of stereotactic radiosurgery in recent years, only systemic treatment was offered to 25 (7%) pts. OS was highly affected by the number of BMs, LDH and albumin level and GPA (Graded Prognostic Assessment) scale (all p < 0.0001). mOS for pts with 1 BM was 10 months, for 2-3 – 7.4 m and for 4+ - 3.6 months. mOS was the longest for pts treated with local therapy (SRS/neurosurgery) combined with immunotherapy. We found significant improvement in OS for BM pts treated after 2013 (p < 0.0001) especially with GPA score 3 or 4 (p < 0.05) - 24-month OS rate 9% vs 28% for pts diagnosed since 2014.
The outcomes of patients with BMs is highly improved when local therapy (neurosurgery +/- SRS) is combined with modern systemic therapy. The introduction of new therapies significantly improved survival of melanoma pts with BMs.
Clinical trial identification
Legal entity responsible for the study
Maria Sklodowska-Curie Institute - Oncology Center, Warsaw, Poland.
Has not received any funding.
I. Lugowska: Honoraria (self), Research grant / Funding (institution): Roche; Honoraria (self): BMS. H. Kosela-Paterczyk: Honoraria (self): Novartis; Honoraria (self): BMS.A.M. Czarnecka: Honoraria (self), Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: BMS; Honoraria (self), Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Novartis. P. Rutkowski: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): BMS; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Novartis; Honoraria (self): Roche; Honoraria (self): Amgen; Speaker Bureau / Expert testimony: Eli Lilly; Advisory / Consultancy: Blueprint Medicines; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Pierre Fabre. All other authors have declared no conflicts of interest.