Scientific publications
Sequential immunotherapy and targeted therapy for metastatic BRAF V600 mutated melanoma: 4-year survival and biomarkers evaluation from the phase II SECOMBIT trial. Scientific Publication
Paolo A Ascierto 1 , Milena Casula 2 , Jenny Bulgarelli 3 , Marina Pisano 2 , Claudia Piccinini 3 , Luisa Piccin 4 , Antonio Cossu 5 , Mario Mandalà 6 7 , Pier Francesco Ferrucci 8 , Massimo Guidoboni 3 , Piotr Rutkowski 9 , Virginia Ferraresi 10 , Ana Arance 11 , Michele Guida 12 , Evaristo Maiello 13 , Helen Gogas 14 , Erika Richtig 15 , Maria Teresa Fierro 16 , Celeste Lebbe 17 , Hildur Helgadottir 18 , Paola Queirolo 19 20 , Francesco Spagnolo 19 , Marco Tucci 21 , Michele Del Vecchio 22 , Maria Gonzales Cao 23 , Alessandro Marco Minisini 24 , Sabino De Placido 25 , Miguel F Sanmamed 21 , Domenico Mallardo 26 , Miriam Paone 26 , Maria Grazia Vitale 26 , Ignacio Melero 27 , Antonio M Grimaldi 26 28 , Diana Giannarelli 29 , Reinhard Dummer 30 , Vanna Chiarion Sileni # 4 , Giuseppe Palmieri # 2
Abstract
No 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.
CITATION Nat Commun. 2024 Jan 2;15(1):146. doi: 10.1038/s41467-023-44475-6
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