Publicaciones científicas

Sequential immunotherapy and targeted therapy for metastatic BRAF V600 mutated melanoma: 4-year survival and biomarkers evaluation from the phase II SECOMBIT trial

02-ene-2024 | Revista: Nature Communications

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


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.

CITA DEL ARTÍCULO  Nat Commun. 2024 Jan 2;15(1):146.  doi: 10.1038/s41467-023-44475-6