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oai:recercat.cat:11351/135032025-09-30T02:07:47Zcom_2072_378070com_2072_378040col_2072_378092

Combined immunotherapy with nivolumab and ipilimumab with and without sequential or concomitant stereotactic radiotherapy in patients with melanoma brain metastasis: An international retrospective study Sergi, Maria Chiara Rasch, Marie-Lena Benannoune, Naima mandala, mario Amaral, Teresa Rutkowski, Piotr MUÑOZ COUSELO, EVA Institut Català de la Salut [Mandalà M] Unit of Medical Oncology, University of Perugia, Perugia, Italy. [Amaral T, Rasch ML] Skin Cancer Clinical Trials Center, Department of Dermatology, Eberhard Karls University, Tuebingen, Germany. [Rutkowski P] Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland. [Sergi MC] Unit of Medical Oncology, "Mons. A.R. Dimiccoli" Hospital, Asl BT, Barletta, Italy. [Benannoune N] Gustave Roussy Cancer Campus, Villejuif, France. [Munoz Couselo E] Servei d’Oncologia Mèdica, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain Vall d'Hebron Barcelona Hospital Campus Cervell - Càncer - Immunoteràpia Cervell - Càncer - Radioteràpia Quimioteràpia combinada Metàstasi Melanoma - Immunoteràpia Melanoma - Radioteràpia ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols DISEASES::Neoplasms::Neoplasms by Site::Nervous System Neoplasms::Central Nervous System Neoplasms::Brain Neoplasms DISEASES::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Germ Cell and Embryonal::Neuroectodermal Tumors::Neuroendocrine Tumors::Melanoma Other subheadings::Other subheadings::/therapy ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Biological Therapy::Immunomodulation::Immunotherapy ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Radiotherapy DISEASES::Neoplasms::Neoplastic Processes::Neoplasm Metastasis TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada ENFERMEDADES::neoplasias::neoplasias por localización::neoplasias del sistema nervioso::neoplasias del sistema nervioso central::neoplasias cerebrales ENFERMEDADES::neoplasias::neoplasias por tipo histológico::neoplasias de células germinales y embrionarias::tumores neuroectodérmicos::tumores neuroendocrinos::melanoma Otros calificadores::Otros calificadores::/terapia TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::terapia biológica::inmunomodulación::inmunoterapia TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::radioterapia ENFERMEDADES::neoplasias::procesos neoplásicos::metástasis neoplásica Comboimmunotherapy; Concomitant radiotherapy; Melanoma brain metastases Inmunoterapia combinada; Radioterapia concomitante; Metástasis cerebrales de melanoma Immunoteràpia combinada; Radioteràpia concomitant; Metàstasis cerebrals de melanoma Background: Ipilimumab plus nivolumab (COMBO) is the standard treatment in patients with asymptomatic melanoma brain metastases (MBM). We report a retrospective study aiming to assess the outcome of patients with MBM treated with COMBO with or without sequential/concomitant stereotactic radiotherapy (SRT). Methods: MBM patients treated with COMBO with or without SRT have been retrieved: demographics, steroid treatment, Central Nervous System [CNS]-related symptoms, BRAF status, radiotherapy (yes/no and timing) or surgery, number of MBM, maximum diameter of metastasis, overall response rate (ORR), progression-free (PFS) and overall survival (OS) have been analyzed. Results: 453 patients were included: 190 received COMBO alone, 107 received COMBO and concomitant SRT, 156 COMBO and sequential SRT, respectively. At multivariable analysis the line of treatment [> 1st vs 1st: HR 2.60 (1.93-3.50)], sequential SRT vs no radiotherapy [HR 0.45 (0.32-0.64)], concomitant SRT vs no radiotherapy [HR 0.48 (0.33-0.69)], steroids [HR 1.56 (1.17-2.08)], age [HR 1.01 (1.00-1.02)] and number of MBM [≥ 3 vs 1 HR 1.55 (1.11-2.17)), 2 vs 1 HR 1.53 (1.02-2.31)] at baseline were associated with OS. There was no significant difference between patients who received concomitant vs sequential SRT. At a median follow-up of 29 months, the median-OS in the overall population was 17.8 months while in those who received SRT was 27.3 (15.3-39.4) for patients receiving sequential radiotherapy and 22.2 (12.7-31.7) for those receiving radiotherapy concomitantly to COMBO. The incidence of radionecrosis was 10.3 %. Toxicities were consistent with previous studies. Conclusions: Our results suggest a better OS in patients who receive SRT plus COMBO, regardless of timing of SRT. Prospective studies are needed to validate our findings. 2025-08-07T07:50:20Z 2025-08-07T07:50:20Z 2025-07-25 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Mandalà M, Amaral T, Rutkowski P, Sergi MC, Rasch ML, Benannoune N, et al. Combined immunotherapy with nivolumab and ipilimumab with and without sequential or concomitant stereotactic radiotherapy in patients with melanoma brain metastasis: an international retrospective study. Eur J Cancer. 2025 Jul 25;225:115567. 0959-8049 http://hdl.handle.net/11351/13503 10.1016/j.ejca.2025.115567 40505525 001510502600001 http://hdl.handle.net/11351/13503 eng European Journal of Cancer;225 https://doi.org/10.1016/j.ejca.2025.115567 Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess application/pdf Elsevier Scientia