Abstract 3175
Background
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.
Methods
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).
Results
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.
Conclusions
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
Editorial acknowledgement
Legal entity responsible for the study
Maria Sklodowska-Curie Institute - Oncology Center, Warsaw, Poland.
Funding
Has not received any funding.
Disclosure
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.
Resources from the same session
3252 - Genes involved in DNA replication, chromatin remodeling and cell cycle as potential biomarkers for therapy outcome to immune therapy in patients with metastatic cutaneous malignant melanoma
Presenter: Fernanda Costa Svedman
Session: Poster Display session 3
Resources:
Abstract
5545 - Phase Ib/II Study (SENSITIZE) assessing safety, pharmacokinetics (PK), pharmacodynamics (PD), and clinical outcome of domatinostat in combination with pembrolizumab in patients with advanced melanoma refractory/non-responding to prior checkpoint inhibitor therapy
Presenter: Jessica Hassel
Session: Poster Display session 3
Resources:
Abstract
5213 - Genomic landscape of primary malignant melanoma of esophagus
Presenter: Jie Dai
Session: Poster Display session 3
Resources:
Abstract
2716 - A phase III, randomised, double-blind study of adjuvant cemiplimab versus placebo post-surgery and radiation in patients with high-risk cutaneous squamous cell carcinoma (CSCC)
Presenter: Danny Rischin
Session: Poster Display session 3
Resources:
Abstract
3550 - ILLUMINATE 301: A randomized phase 3 study of tilsotolimod in combination with ipilimumab compared with ipilimumab alone in patients with advanced melanoma following progression on or after anti-PD-1 therapy
Presenter: Marcus Butler
Session: Poster Display session 3
Resources:
Abstract
1645 - PRIME002 - Early phase II study of Azacitidine and Carboplatin priming for Avelumab in patients with advanced melanoma who are resistant to immunotherapy
Presenter: Andre Van Der Westhuizen
Session: Poster Display session 3
Resources:
Abstract
4440 - Pembrolizumab (pembro) Plus Lenvatinib (len) for First-Line Treatment of patients (pts) With Advanced Melanoma: Phase 3 LEAP-003 Study
Presenter: Alexander Eggermont
Session: Poster Display session 3
Resources:
Abstract
3454 - Proof of concept study with the histone deacetylase inhibitor vorinostat in patients with resistant BRAFV600 mutated advanced melanoma
Presenter: Sanne Huijberts
Session: Poster Display session 3
Resources:
Abstract
1832 - A phase Ia/Ib clinical study to evaluate the safety, pharmacokinetics (PK) and preliminary anti-tumor activity of FCN-159 in patients with advanced melanoma harboring NRAS-aberrant (Ia) and NRAS-mutation (Ib).
Presenter: Lu Si
Session: Poster Display session 3
Resources:
Abstract
3996 - A Phase I Clinical Trial Investigating the Therapeutic Cancer Vaccine UV1 in Combination with Pembrolizumab as First-Line Treatment of Patients with Malignant Melanoma
Presenter: Sanjiv Agarwala
Session: Poster Display session 3
Resources:
Abstract