Abstract
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.
| Original language | English |
|---|---|
| Article number | e000333 |
| Journal | Journal for ImmunoTherapy of Cancer |
| Volume | 8 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 26.03.2020 |
Funding
TA: reports personal fees and travel grants from BMS, grants, personal fees and travel grants from Novartis, personal fees from Pierre Fabre, grants from Neracare, grants from Sanofi, outside the submitted work. FK: reports personal fees from Amgen, personal fees from BMS, personal fees from MSD, grants and personal fees from Novartis, personal fees from Pierre Fabre, personal fees from Roche, personal fees from Sanofi, outside the submitted work. CL: reports personal fees from BMS, personal fees from MSD, personal fees from Merck, personal fees from Novartis, personal fees from Roche, personal fees from Pierre Fabre, personal fees from Sanofi, personal fees from Amgen, personal fees from Biontech, personal fees from Sun Pharma, other from Kiowa Kirin, outside the submitted work. KK: reports grants and personal fees from BMS, personal fees from MSD, during the conduct of the study; personal fees from Amgen, grants and personal fees from NeraCare, grants and personal fees from Novartis, personal fees from Philogen, grants and personal fees from Roche, grants and personal fees from Sanofi, outside the submitted work. PT: reports personal fees from BMS, Novartis, MSD, Pierre Fabre, CureVac and Roche, personal fees from BMS, Novartis, Pierre Fabre, Merck Serono, Sanofi and Roche, non-financial support from BMS, Pierre Fabre and Roche, outside the submitted work. AG: reports personal fees from BMS, personal fees from MSD, personal fees from Novartis, personal fees from Pierre Fabre, personal fees from Pfizer, personal fees from Roche, personal fees from Sanofi, outside the submitted work. RG: reports honoraria: Almirall Hermal, Amgen, Bristol-Myers Squibb (BMS), Incyte, Merck Serono, MSD, Novartis, Pierre Fabre, Pfizer, Roche, SUN; research funding: Amgen, Johnson & Johnson, MerckSerono, Novartis, Pfizer; travel and accommodations: BMS, Merck Serono, Pierre Fabre, Roche, SUN, outside the submitted work. SH: reports grants and personal fees from BMS, personal fees from MSD, during the conduct of the study; personal fees from Amgen, personal fees from Novartis, personal fees from Roche, personal fees from Sanofi, personal fees from Pierre Fabre, outside the submitted work. JU: is on the advisory board or has received honoraria and travel support from Amgen, BMS, GSK, LeoPharma, Merck Sharp & Dohme (MSD), Novartis, Pierre Fabre, Roche, Sanofi outside the submitted work. CB: has been investigator of clinical trials sponsored by Amgen, Array Pharma, BMS, ImmunoCore, MSD, Novartis, Regeneron and Roche; has received speaker’s and/or consultant’s fees by Amgen, BMS, ImmunoCore, Merck, MSD, Novartis, Pierre Fabre, Roche, Sanofi-Aventis and SunPharma, outside the submitted work. DR-S: reports personal fees from Novartis, personal fees from Roche, outside the submitted work. AK: reports advisory board honoraria from Novartis Pharma, Roche, travel grants from Amgen and BMS, personal fees from AbbVie and Medac Pharma, outside the submitted work. ChP: reports personal fees from BMS, MSD, Roche, Pierre Fabre, Novatris and SUNPharma for advisory roles during the conduct of the study. TG: reports receiving speakers and/or advisory board honoraria from BMS, Sanofi-Genzyme, MSD, Novartis Pharma, Roche, AbbVie, Almirall, Janssen, Lilly, Pfizer, Pierre Fabre, outside the submitted work. ClP: reports personal fees from BMS, personal fees from MSD, during the conduct of the study; personal fees from Amgen, personal fees from Merck Serono, personal fees from Novartis, personal fees from Roche, personal fees from Sanofi, personal fees from Pierre Fabre, outside the submitted work. DD: reports consulting and speaking fees and/or payment of travel expenses/participation fees: Amgen, BMS, MSD, Mylan, Novartis, Pierre Fabre, Roche, Sanofi, outside the submitted work. RH: served as consultant and/or has received speakers’ honoraria from Roche, BMS, MSD, Novartis and Pierre Fabre outside the submitted work. SE: reports advice and speakers’ honoraria from MSD, BMS, Pierre Fabre, Sanofi, Amgen, Novartis, LEO Pharm, ROCHE and Genzyme Corporation, outside the submitted work. JCH: reports personal fees and travel grants from BMS, MSD, Novartis, Roche, Pfizer, Pierre Fabre and Sanofi, grants for scientific projects from BMS, personal fees for participation in advisory boards from MSD and Pierre Fabre, outside the submitted work. FM: reports personal fees and non-financial support from Novartis, personal fees and non-financial support from Roche, personal fees from MSD, personal fees and non-financial support from BMS, personal fees and non-financial support from Pierre Fabre, outside the submitted work. TT: reports grants and personal fees from Novartis, grants and personal fees from Roche, outside the submitted work. TE: reports personal fees from Amgen, grants and personal fees from BMS, personal fees from MSD, grants and personal fees from Novartis, personal fees from Pierre Fabre, grants and personal fees from Roche, grants and personal fees from Sanofi, outside the submitted work. CG: reports grants and personal fees from BMS, personal fees from MSD, during the conduct of the study; personal fees from Amgen, grants and personal fees from NeraCare, grants and personal fees from Novartis, personal fees from Philogen, grants and personal fees from Roche, grants and personal fees from Sanofi, outside the submitted work. LZ: served as consultant and/or has received honoraria from Roche, BMS, MSD, Novartis, Pierre Fabre, Sanofi, and travel support from MSD, BMS, Amgen, Pierre Fabre, Sanofi and Novartis, outside the submitted work.
Research Areas and Centers
- Academic Focus: Center for Infection and Inflammation Research (ZIEL)
