Sequential immunotherapy and targeted therapy for metastatic BRAF V600 mutated melanoma: 4-year survival and biomarkers evaluation from the phase II SECOMBIT trial
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Published:2024-01-02
Issue:1
Volume:15
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Ascierto Paolo A.ORCID, Casula Milena, Bulgarelli JennyORCID, Pisano Marina, Piccinini Claudia, Piccin Luisa, Cossu Antonio, Mandalà MarioORCID, Ferrucci Pier FrancescoORCID, Guidoboni MassimoORCID, Rutkowski PiotrORCID, Ferraresi Virginia, Arance AnaORCID, Guida Michele, Maiello Evaristo, Gogas Helen, Richtig Erika, Fierro Maria Teresa, Lebbe CelesteORCID, Helgadottir Hildur, Queirolo Paola, Spagnolo Francesco, Tucci Marco, Del Vecchio Michele, Cao Maria GonzalesORCID, Minisini Alessandro Marco, De Placido Sabino, Sanmamed Miguel F.ORCID, Mallardo DomenicoORCID, Paone Miriam, Vitale Maria Grazia, Melero IgnacioORCID, Grimaldi Antonio M., Giannarelli Diana, Dummer ReinhardORCID, Sileni Vanna ChiarionORCID, Palmieri GiuseppeORCID
Abstract
AbstractNo prospective data were available prior to 2021 to inform selection between combination BRAF and MEK inhibition versus dual blockade of programmed cell death protein-1 (PD-1) and cytotoxic T lymphocyte antigen-4 (CTLA-4) as first-line treatment options for BRAFV600-mutant melanoma. SECOMBIT (NCT02631447) was a randomized, three-arm, noncomparative phase II trial in which patients were randomized to one of two sequences with immunotherapy or targeted therapy first, with a third arm in which an 8-week induction course of targeted therapy followed by a planned switch to immunotherapy was the first treatment. BRAF/MEK inhibitors were encorafenib plus binimetinib and checkpoint inhibitors ipilimumab plus nivolumab. Primary outcome of overall survival was previously reported, demonstrating improved survival with immunotherapy administered until progression and followed by BRAF/MEK inhibition. Here we report 4-year survival outcomes, confirming long-term benefit with first-line immunotherapy. We also describe preliminary results of predefined biomarkers analyses that identify a trend toward improved 4-year overall survival and total progression-free survival in patients with loss-of-function mutations affecting JAK or low baseline levels of serum interferon gamma (IFNy). These long-term survival outcomes confirm immunotherapy as the preferred first-line treatment approach for most patients with BRAFV600-mutant metastatic melanoma, and the biomarker analyses are hypothesis-generating for future investigations of predictors of durable benefit with dual checkpoint blockade and targeted therapy.
Funder
This study was supported by unconditioned grants from Bristol-Myers Squibb (Princeton, NJ) and Array Biopharma Inc./Pfizer (Boulder, CO).
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
Reference64 articles.
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