RT Journal Article
SR Electronic
T1 Combined immunotherapy with nivolumab and ipilimumab with and without local therapy in patients with melanoma brain metastasis: a DeCOG* study in 380 patients
JF Journal for ImmunoTherapy of Cancer
JO J Immunother Cancer
FD BMJ Publishing Group Ltd
SP e000333
DO 10.1136/jitc-2019-000333
VO 8
IS 1
A1 Teresa Amaral
A1 Felix Kiecker
A1 Sarah Schaefer
A1 Henner Stege
A1 Katharina Kaehler
A1 Patrick Terheyden
A1 Anja Gesierich
A1 Ralf Gutzmer
A1 Sebastian Haferkamp
A1 Jochen Uttikal
A1 Carola Berking
A1 David Rafei-Shamsabadi
A1 Lydia Reinhardt
A1 Friedegund Meier
A1 Ante Karoglan
A1 Christian Posch
A1 Thilo Gambichler
A1 Claudia Pfoehler
A1 Kai Thoms
A1 Julia Tietze
A1 Dirk Debus
A1 Rudolf Herbst
A1 Steffen Emmert
A1 Carmen Loquai
A1 Jessica C Hassel
A1 Frank Meiss
A1 Thomas Tueting
A1 Vanessa Heinrich
A1 Thomas Eigentler
A1 Claus Garbe
A1 Lisa Zimmer
A1 ,
YR 2020
UL http://jitc.bmj.com/content/8/1/e000333.abstract
AB Background Nivolumab combined with ipilimumab have shown activity in melanoma brain metastasis (MBM). However, in most of the clinical trials investigating immunotherapy in this subgroup, patients with symptomatic MBM and/or prior local brain radiotherapy were excluded. We studied the efficacy of nivolumab plus ipilimumab alone or in combination with local therapies regardless of treatment line in patients with asymptomatic and symptomatic MBM.Methods Patients with MBM treated with nivolumab plus ipilimumab in 23 German Skin Cancer Centers between April 2015 and October 2018 were investigated. Overall survival (OS) was evaluated by Kaplan-Meier estimator and univariate and multivariate Cox proportional hazard analyses were performed to determine prognostic factors associated with OS.Results Three hundred and eighty patients were included in this study and 31% had symptomatic MBM (60/193 with data available) at the time of start nivolumab plus ipilimumab. The median follow-up was 18 months and the 2 years and 3 years OS rates were 41% and 30%, respectively. We identified the following independently significant prognostic factors for OS: elevated serum lactate dehydrogenase and protein S100B levels, number of MBM and Eastern Cooperative Oncology Group performance status. In these patients treated with checkpoint inhibition first-line or later, in the subgroup of patients with BRAFV600-mutated melanoma we found no differences in terms of OS when receiving first-line either BRAF and MEK inhibitors or nivolumab plus ipilimumab (p=0.085). In BRAF wild-type patients treated with nivolumab plus ipilimumab in first-line or later there was also no difference in OS (p=0.996). Local therapy with stereotactic radiosurgery or surgery led to an improvement in OS compared with not receiving local therapy (p=0.009), regardless of the timepoint of the local therapy. Receiving combined immunotherapy for MBM in first-line or at a later time point made no difference in terms of OS in this study population (p=0.119).Conclusion Immunotherapy with nivolumab plus ipilimumab, particularly in combination with stereotactic radiosurgery or surgery improves OS in asymptomatic and symptomatic MBM.