Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Ascierto, PA; Mandalà, M; Ferrucci, PF; Guidoboni, M; Rutkowski, P; Ferraresi, V; Arance, A; Guida, M; Maiello, E; Gogas, H; Richtig, E; Quaglino, P; Lebbé, C; Helgadottir, H; Queirolo, P; Spagnolo, F; Tucci, M; Del, Vecchio, M; Gonzalez-Cao, M; Minisini, AM; De, Placido, S; Sanmamed, MF; Casula, M; Bulgarelli, J; Pisano, M; Piccinini, C; Piccin, L; Cossu, A; Mallardo, D; Paone, M; Vitale, MG; Melero, I; Grimaldi, AM; Giannarelli, D; Palmieri, G; Dummer, R; Sileni, VC.
Sequencing of Checkpoint or BRAF/MEK Inhibitors on Brain Metastases in Melanoma.
NEJM Evid. 2024; 3(10): EVIDoa2400087
Doi: 10.1056/EVIDoa2400087
PubMed
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- Co-Autor*innen der Med Uni Graz
- Richtig Erika
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- Abstract:
- BACKGROUND: The impact of the order of treatment with checkpoint inhibitors or BRAF/MEK inhibitors on the development of brain metastases in patients with metastatic unresectable BRAFV600-mutant melanoma is unknown. The SECOMBIT trial examined the impact of the order of receipt of these treatments in such patients. METHODS: In this three-arm trial, we reviewed patients without brain metastases who received the BRAF/MEK inhibitors encorafenib and binimetinib until they had progressive disease followed by the immune checkpoint inhibitors ipilimumab and nivolumab (arm A); or treatment with ipilimumab and nivolumab until they had progressive disease followed by encorafenib and binimetinib (arm B); or treatment with encorafenib and binimetinib for 8 weeks followed by ipilimumab and nivolumab until they had progressive disease followed by retreatment with encorafenib arm binimetinib (arm C). RESULTS: Brain metastases were discovered during the trial in 23/69 patients in arm A, 11/69 in arm B, and 9/68 in arm C. At a median follow-up of 56 months, the 60-month brain metastases-free survival rates were 56% for arm A, 80% for arm B (hazard ratio [HR] vs. A: 0.40, 95% confidence interval [CI] 0.23 to 0.58), and 85% for arm C (HR vs. A: 0.35, 95% CI 0.16 to 0.76). CONCLUSIONS: In patients with unresectable metastatic melanoma, the treatment sequence of immune checkpoint inhibition followed by BRAF/MEK inhibitors was associated with longer periods of new brain metastases-free survival than the reverse sequence. A regimen in which immune checkpoint inhibition was sandwiched between BRAF/MEK inhibition also appeared to be protective against brain metastases. (ClinicalTrials.gov number NCT02631447.).
- Find related publications in this database (using NLM MeSH Indexing)
- Humans - administration & dosage
- Melanoma - drug therapy, secondary, pathology, genetics
- Brain Neoplasms - secondary, drug therapy
- Female - administration & dosage
- Male - administration & dosage
- Proto-Oncogene Proteins B-raf - antagonists & inhibitors, genetics
- Middle Aged - administration & dosage
- Carbamates - therapeutic use, pharmacology, administration & dosage
- Immune Checkpoint Inhibitors - therapeutic use, pharmacology, administration & dosage
- Benzimidazoles - therapeutic use, pharmacology, administration & dosage
- Nivolumab - therapeutic use, pharmacology, administration & dosage
- Sulfonamides - therapeutic use, pharmacology, administration & dosage
- Aged - administration & dosage
- Ipilimumab - therapeutic use, pharmacology, administration & dosage
- Protein Kinase Inhibitors - therapeutic use, pharmacology, administration & dosage
- Adult - administration & dosage
- Antineoplastic Combined Chemotherapy Protocols - therapeutic use, pharmacology